Evaluation of gallbladder motility assessed by ultrasonography in dogs with hyperlipidemia.

BACKGROUND: The pathogenesis of gallbladder (GB) mucoceles in dogs is unknown. It has been proposed that hyperlipidemia could impair GB motility and contribute to GB mucocele formation. HYPOTHESIS/OBJECTIVES: The objective of this study was to compare GB motility in dogs with hyperlipidemia to control dogs using ultrasonography. We hypothesized that hyperlipidemic dogs will have decreased GB motility compared with controls. ANIMALS: Twenty-six hyperlipidemic and 28 healthy, age-matched control dogs were prospectively enrolled. METHODS: Cholesterol and triglyceride concentrations were measured in all dogs. Hyperlipidemia was defined as hypercholesterolemia (>332 mg/dL) and/or hypertriglyceridemia (>143 mg/dL) using a biochemical analyzer. Ultrasound was performed before feeding, and 60 and 120 minutes after ingestion of a high fat diet. Gallbladder volumes (GBV) and ejection fractions (EF) were calculated. RESULTS: Hyperlipidemic dogs had significantly larger GBVs (ml/kg) before feeding and 60 minutes after feeding of 1.2 (0.4-7.5; P = .008) and 0.6 (0.1-7.2; P = .04) compared with controls 0.6 (0.2-2.6) and 0.4 (0.1-1.9), respectively. Severely hyperlipidemic dogs had significantly larger GBV at baseline, 60 minutes, and 120 minutes of 1.7 (0.6-7.5; P = .03), 1.3 (0.4-7.2; P = .02), and 1.3 (0.2-8.2; P = .04), respectively compared with mildly hyperlipidemic dogs. EFs at 60 and 120 minutes between controls, hyperlipidemic, and severely hyperlipidemic were all 0.3 at 60 minutes and 0.5, 0.3, and 0.3 at 120 minutes, respectively which were not statistically different. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperlipidemia leads to GB distention in dogs which could lead to retention of bile and gallbladder disease.

Comparison of linear and volumetric criteria for the determination of therapeutic response in dogs with intracranial gliomas.

BACKGROUND: Brain tumor therapeutic responses can be quantified from magnetic resonance images (MRI) using 1- (1D) and 2-dimensional (2D) linear and volumetric methods, but few studies in dogs compare these techniques. HYPOTHESES: Linear methods will be obtained faster, but have less agreement than volumetric measurements. Therapeutic response agreement will be highest with the total T2W tumor volumetric (TTV) method. Therapeutic response at 6-weeks will correlate with overall survival (OS). ANIMALS: Forty-six dogs with intracranial gliomas. METHODS: Prospective study. Three raters measured tumors using 1D and 2D linear, TTV, and contrast-enhancing volumetric (CEV) techniques on 143 brain MRI to determine agreement between methods, define therapeutic responses, and assess relations with OS. RESULTS: Raters performed 1D the fastest (2.9 ± 0.57 minutes) and CEV slowest (17.8 ± 6.2 minutes). Inter- and intraobserver agreements were excellent (intraclass correlations ≥.91) across methods. Correlations between linear (1D vs 2D; ρ > .91) and volumetric (TTV vs CEV; ρ > .73) methods were stronger than linear to volumetric comparisons (ρ range, .26-.59). Incorporating clinical and imaging data resulted in fewer discordant therapeutic responses across methods. Dogs having partial tumor responses at 6 weeks had a lower death hazard than dogs with stable or progressive disease when assessed using 2D, CEV, and TTV (hazard ration 2.1; 95% confidence interval, 1.22-3.63; P = .008). CONCLUSIONS AND CLINICAL IMPORTANCE: One-dimensional, 2D, CEV, and TTV are comparable for determining therapeutic response. Given the simplicity, universal applicability, and superior performance of the TTV, we recommend its use to standardize glioma therapeutic response criteria.

Histotripsy Ablation in Preclinical Animal Models of Cancer and Spontaneous Tumors in Veterinary Patients: A Review.

New therapeutic strategies are direly needed in the fight against cancer. Over the last decade, several tumor ablation strategies have emerged as stand-alone or combination therapies. Histotripsy is the first completely noninvasive, nonthermal, and nonionizing tumor ablation method. Histotripsy can produce consistent and rapid ablations, even near critical structures. Additional benefits include real-time image guidance, high precision, and the ability to treat tumors of any predetermined size and shape. Unfortunately, the lack of clinically and physiologically relevant preclinical cancer models is often a significant limitation with all focal tumor ablation strategies. The majority of studies testing histotripsy for cancer treatment have focused on small animal models, which have been critical in moving this field forward and will continue to be essential for providing mechanistic insight. While these small animal models have notable translational value, there are significant limitations in terms of scale and anatomical relevance. To address these limitations, a diverse range of large animal models and spontaneous tumor studies in veterinary patients have emerged to complement existing rodent models. These models and veterinary patients are excellent at providing realistic avenues for developing and testing histotripsy devices and techniques designed for future use in human patients. Here, we provide a review of animal models used in preclinical histotripsy studies and compare histotripsy ablation in these models using a series of original case reports across a broad spectrum of preclinical animal models and spontaneous tumors in veterinary patients.

Bile duct obstruction associated with pancreatitis in 46 dogs.

BACKGROUND: Pancreatitis is a common cause of extrahepatic bile duct obstruction (EHBDO) in dogs. Information describing the clinical course of dogs with pancreatitis associated bile duct obstruction (PABDO) is limited. OBJECTIVES: To describe the clinical course of PABDO in dogs and determine if presumed markers of disease severity are predictors of survival. ANIMALS: Forty-six client-owned dogs with PABDO. METHODS: A retrospective review of medical records from dogs diagnosed with PABDO was performed. Data, including clinical signs and biochemical changes, were collected 6 times throughout the course of disease. Outcome was defined as either survival (discharge from the hospital) or death. RESULTS: Thirty-three (79%) out of 42 dogs with PABDO survived. Thirty-one (94%) of the 33 dogs that survived received medical management alone. Time from onset of clinical signs to initial documented increase in serum bilirubin concentration, peak bilirubin elevation, and initial decline in serum bilirubin concentration were 7 (median), 8, and 15 days, respectively. The median number of days from onset of clinical signs to outcome date was 13. Clinical signs of fever, vomiting, and anorexia were decreased in frequency from the onset of clinical signs to the time of peak bilirubin. Median bile duct dilatation at the time of ultrasonographic diagnosis of PABDO and peak bilirubin were not different between survivors (7.6 mm, 11.7 mg/dL) and nonsurvivors (6 mm, 10.6 mg/dL, P = .12, P = .8). CONCLUSIONS: Dogs with PABDO often have a prolonged course of illness and improve clinically despite biochemical evidence of progression of EHBDO.

Diffusion weighted magnetic resonance imaging is a feasible method for characterizing regional lymph nodes in canine patients with head and neck disease.

In dogs diagnosed with solid tumors, regional lymph node involvement or evidence of distant metastasis can predict worse prognoses and significantly decreased survival. Lymph node size alone has been shown to be insufficient as a predictor for the accurate clinical staging of some canine neoplasia. However, certain regional lymph nodes (including those of the oral cavity) are difficult to access for routine tissue sampling. Diffusion weighted magnetic resonance imaging (MRI) has demonstrated the ability to differentiate metastatic from inflammatory/benign lymph nodes in clinical studies with human cancer patients through the calculation of quantitative values of diffusion termed apparent diffusion coefficients (ADC). The objective of this prospective, exploratory study was to evaluate diffusion-weighted MRI and ADC as potential methods for detecting metastatic lymph nodes in dogs with naturally occurring disease. We hypothesized that diffusion-weighted MRI would identify significantly different ADC values between benign and metastatic lymph nodes in a group of canine patients with head or neck disease. Our study population consisted of eight client-owned canine patients, with a total of 20 lymph nodes evaluated (six metastatic, 14 benign). Our results demonstrated that two of four observers identified a significant difference between the mean ADC values of the benign and metastatic lymph nodes. When data from all four observers were pooled, the difference between the mean apparent diffusion coefficients values of the benign and metastatic lymph nodes did not reach significance (P-value = 0.0566). Findings indicated that diffusion-weighted MRI is a feasible method for further characterizing enlarged lymph nodes in dogs with head and neck disease, however measured ADC values did not differ for benign vs. metastatic lymph nodes in this small sample of dogs.

Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study.

INTRODUCTION: The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. METHODS: Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0-2. Patients took vorinostat 400 mg PO daily days 1-14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design. RESULTS: Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1-6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. CONCLUSIONS: Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients.

Feasibility and accuracy of ultrasound-guided sacroiliac joint injection in dogs.

Frozen cadaver specimens from three dogs were used to create a sectional anatomic atlas of the sacroiliac region. Frozen/thawed cadaver specimens from 12 dogs were used to develop an ultrasound-guided sacroiliac joint injection technique. Accuracy of the technique was tested in 15 additional canine cadaver specimens, using injectate containing blue dye and iodinated contrast medium. Sonoanatomic landmarks for consistently identifying a caudodorsal window into the canine sacroiliac joint space included the L7-S1 articular process joints, ilial wing, sacral wing, sacral lamina, and median sacral crest. Accuracy of ultrasound-guided sacroiliac joint injection was not significantly affected by operator, but was affected by the tissue location targeted and the reference standard used for calculations. Accuracy of the technique was good for placing injectate into either the synchondrosis component, dorsal sacroiliac ligament or ventral sacroiliac ligament; fair to poor for placing injectate into the synovial component; and poor for placing injectate into all four sacroiliac soft tissue structures. Concurrent placement of injectate into extraarticular tissues occurred frequently. We conclude that ultrasound-guided sacroiliac joint injection is feasible for evaluation as a treatment method for lumbosacral region pain in dogs, but is not sufficiently accurate for localizing pain to the sacroiliac joint alone.

Phase I study of sunitinib and erlotinib in advanced nonsquamous non-small cell lung cancer.

INTRODUCTION: Erlotinib has prolonged survival in unselected patients with advanced non-small cell lung cancer, whereas sunitinib has yielded promising rates of disease control in previously treated patients. We conducted a dose escalation study of this combination to determine the maximum tolerated dose of sunitinib in combination with a fixed dose of erlotinib and to evaluate the toxicities of this combination. METHODS: Patients with advanced nonsquamous non-small cell lung cancer were treated at two dose levels: sunitinib at either 25 mg or 37.5 mg, with erlotinib 150 mg. Both drugs were given once daily, continuously. RESULTS: Eleven patients enrolled from November 2007 to October 2009. No dose-limiting toxicities occurred. Grade 3/4 adverse events at least possibly related to treatment were seen in seven patients (64%). Six patients (54%) required dose modifications, and three (27%) discontinued study treatment due to toxicity. Rates of grade 3 diarrhea and mucositis exceeded those seen with single-agent erlotinib or sunitinib. One patient (9%) attained a partial response lasting 16.3 months. CONCLUSIONS: Although no dose-limiting toxicities occurred, it is difficult to recommend erlotinib 150 mg and sunitinib 37.5 mg daily as the phase II dose for this combination due to the high rate of adverse events. Because of the overlapping toxicity profile of each agent, this combination was poorly tolerated in our population.

Modeling of the spread of infection in the interdigital spaces of the manus in limbs from clinically normal dogs.

OBJECTIVE: To determine whether the pattern of extension of modeled infection from the interdigital web spaces in dogs is predictable and whether the distribution differs among initial injury sites. SAMPLE POPULATION: Thawed frozen forelimbs from 23 cadavers of previously healthy adult medium- to large-breed dogs. PROCEDURES: The manus of each forelimb was evaluated by use of computed tomography (CT) before and after injection of radiopaque blue-staining contrast medium into the interdigital web spaces. Two veterinary radiologists reviewed the CT images and recorded the extent of contrast medium from each site. Each manus was dissected or sectioned transversely after imaging, and the extent of contrast medium accumulation was recorded and compared with locations of CT contrast enhancement. The Fisher exact test was performed to determine whether the pattern of contrast medium extension differed by injection site. RESULTS: Injections made in the interdigital web spaces of the canine manus led to unique and predictable patterns of extension into the surrounding soft tissues. That pattern of extension primarily involved the soft tissues of the digits. CONCLUSIONS AND CLINICAL RELEVANCE: In humans, knowledge of common extension patterns from infected soft tissue spaces is used to predict the spread of disease within the hand and develop surgical plans that will minimize patient illness. Identification of the common sites of disease spread from the interdigital web spaces in dogs may help improve surgical planning and treatment for infection in the manus.

Computed tomographic and cross-sectional anatomic characterization of myofascial compartments and soft tissue spaces in the manus in cadavers of dogs without forelimb disease.

OBJECTIVE: To characterize the computed tomographic (CT) and cross-sectional anatomic features of myofascial compartments and soft tissue spaces in the manus of cadavers of dogs without forelimb disease. ANIMALS: 33 cadavers of adult medium- to large-breed dogs without forelimb disease. PROCEDURES: Forelimbs were removed from the cadavers within 4 hours after euthanasia or within 6 hours after thawing from initial freezing. Specimens were then frozen for variable periods and thawed for approximately 16 hours before use. Each manus of 60 forelimbs underwent CT before and after injection of a radiopaque, blue-staining contrast medium into locations where soft tissue spaces and myofascial compartments were predicted (on the basis of pilot study data [6 forelimbs]). Two veterinary radiologists reviewed CT images and recorded the presence or absence of a discrete space or compartment at each injection site. Each manus was subsequently dissected or sectioned transversely. Locations of blue-staining contrast medium accumulation were compared with locations of contrast enhancement in CT images. Anatomic structures within each soft tissue space or myofascial compartment were described. RESULTS: 13 soft tissue spaces and 5 myofascial compartments were identified in the manus. Three myofascial structures that were examined were determined not to be compartments. CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of soft tissue spaces and myofascial compartments are used to map the likely spread of disease in the hands and feet of humans. Thus, understanding the locations and extent of similar structures in the canine manus may improve the effectiveness of surgical interventions in dogs with injury or inflammation of this region of the forelimb.

Diffuse osteopenia and myelopathy in a puppy fed a diet composed of an organic premix and raw ground beef.

CASE DESCRIPTION: An 8-month-old Shetland Sheepdog was evaluated because of the sudden onset of signs of neck pain, collapse, and inability to rise. A cursory diet history indicated that the dog had been fed a raw meat-based diet. CLINICAL FINDINGS: Initial evaluation of the dog revealed small physical stature, thin body condition, and signs of cranial cervical myelopathy. Radiographically, diffuse osteopenia of all skeletal regions was identified; polyostotic deformities associated with fracture remodeling were observed in weight-bearing bones, along with an apparent floating dental arcade. Hypocalcemia and hypophosphatemia were detected via serum biochemical analyses. The dog's diet was imbalanced in macronutrients and macrominerals. TREATMENT AND OUTCOME: The dog received supportive care and treatment of medical complications; neurologic abnormalities improved rapidly without intervention. Dietary changes were implemented during hospitalization, and a long-term feeding regimen was established. Following discharge from the hospital, exercise restriction was continued at home. Serial follow-up evaluations, including quantitative bone density measurements, revealed that dietary changes were effective. After 7 months, the dog was clinically normal. CLINICAL RELEVANCE: In the dog of this report, vitamin D-dependent rickets type I and suspected nutritional secondary hyperparathyroidism developed following intake of a nutritionally incomplete and unbalanced diet. The raw meat-based, home-prepared diet fed to the dog was not feed-trial tested for any life stage by the Association of American Feed Control Officials, and its gross nutrient imbalance induced severe metabolic, orthopedic, and neurologic abnormalities. Inadvertent malnutrition can be avoided through proper diet assessment and by matching nutrient profiles with patients' nutritional needs.

Phase I/II study of vinorelbine and exisulind as first-line treatment of advanced non-small cell lung cancer in patients at least 70 years old: a wisconsin oncology network study.

INTRODUCTION: Exisulind is an apoptotic agent with preclinical activity in non-small cell lung cancer (NSCLC). Vinorelbine is safe and effective in older patients with advanced NSCLC. We assessed these agents together as palliative treatment for older patients with advanced NSCLC. METHODS: Chemotherapy-naive patients >/=70-years-old with stage IIIB-IV NSCLC and a performance status (PS) /=3 neutropenia occurred in 14/30 patients. Two patients experienced neutropenic fever. There were no complete responses, one partial response and 12 patients with stable disease as their best response. The objective response rate was 4.0% (95% CI: 0.1-20.4%). Phase II median time-to-progression was 4.7 months (95% CI: 3.1-9.3 months) and median OS was 9.6 months (95% CI: 6.6-19.1 months). CONCLUSIONS: This combination is safe, seems to have activity in the elderly with advanced NSCLC and a PS

Effect of nephrotomy on renal function and morphology in normal cats.

OBJECTIVE: To assess effects over 12 weeks of bisection nephrotomy on renal function, size, and morphology in cats. STUDY DESIGN: Controlled, randomized, blinded experiment. SAMPLE POPULATION: Ten adult female cats. METHODS: Glomerular filtration rate (GFR), determined by quantitative renal scintigraphy using (99m)Technetium-diethylenetriamine-pentaacetic acid, urinalysis, urine culture, and ultrasonographic measurement of renal size were performed preoperatively. Left or right nephrotomy (5 cats/group) was performed. Total and individual kidney GFRs were determined at 2, 28, and 84 days, ultrasonographic measurements at 28 and 86 days, and ultrasound-guided biopsy at 86 days. RESULTS: No significant differences in mean GFR and kidney size of operated versus unoperated kidneys were observed. Individual GFR and renal size of all except 1 cat remained within normal limits. Two cats had evidence of transient ureteral obstruction in the immediate postoperative period. No significant, generalized histologic abnormalities were observed. CONCLUSIONS: Bisection nephrotomy in normal cats does not adversely affect renal function or morphology during the initial 12 weeks. CLINICAL RELEVANCE: Bisection nephrotomy can be safely performed in normal feline kidneys without causing a significant deleterious effect on renal function. Studies in cats with pre-existing renal insufficiency are needed to ensure adverse effects would not occur in clinical cases where this surgical procedure is warranted.

Comparative performance of radiography and computed tomography in the diagnosis of middle ear disease in 31 dogs.

The purpose of this study was to compare computed tomography (CT) and radiography for diagnosing the presence and severity of middle ear disease in dogs with a history of chronic otitis externa. Thirty-one dogs undergoing a total ear canal ablation and bulla osteotomy were studied. Three normal dogs served as controls. All dogs were examined using radiography and CT. Three radiologists independently evaluated imaging studies in random order. A visual analog scale method was used for scoring certainty and severity of middle ear disease. Surgical findings were recorded intra-operatively. Bulla lining samples were submitted for histopathologic evaluation and scored by a single pathologist who also used a visual analog scale system. Findings from both imaging modalities agreed more closely with surgical findings than with histopathologic findings. With either surgical or histopathologic findings as the gold standard, CT was more sensitive than and as specific as radiographs for predicting presence and severity of middle ear disease. Observer performance with CT was more consistent than the performance with radiographs in the detection of changes that occur with middle ear disease. Both radiography and CT were more accurate for predicting the severity of the disease than its presence. Findings indicate that CT is more accurate and reliable than radiography in diagnosing middle ear disease for dogs having concurrent otitis externa, but only when severity of disease is moderate or high. With low severity of disease, diagnostic certainty for both modalities becomes more variable.