A Nonselective Cyclooxygenase Inhibitor Enhances the Activity of Vinblastine in a Naturally-Occurring Canine Model of Invasive Urothelial Carcinoma.

Background: Chemotherapy is expected to remain an important part of invasive urothelial carcinoma (UC) treatment. Strategies to enhance chemotherapy efficacy are needed. Objective: To determine the chemotherapy-enhancing effects of a nonselective cyclooxygenase (COX) inhibitor on vinblastine in a naturally-occurring canine model of invasive UC. Methods: With IACUC approval, privately-owned dogs with naturally-occurring histologically-diagnosed invasive UC, expected survival ≥6 weeks, and informed owner consent were randomly allocated to receive vinblastine (2.5 mg/m2 intravenously every 2 weeks) plus piroxicam (0.3 mg/kg daily per os) or vinblastine alone (same dose) with the option to receive piroxicam alone when vinblastine failed. Scheduled evaluations included physical exam, standard laboratory analyses, thoracic radiography, abdominal ultrasonography, and standardized measurement of urinary tract tumors. Results: Dogs receiving vinblastine alone (n = 27) and vinblastine-piroxicam (n = 24) were similar in age, sex, breed, tumor stage, and grade. Remission occurred more frequently (P <  0.02) with vinblastine-piroxicam (58.3%) than with vinblastine alone (22.2%). The median progression free interval was 143 days with vinblastine alone and 199 days with the combination. Interestingly, the overall median survival time was significantly longer (P <  0.03) in dogs receiving vinblastine alone followed by piroxicam alone (n = 20, 531 days) than in dogs receiving the combination (299 days). Treatment was well tolerated in both arms. Conclusions: Piroxicam significantly enhanced the activity of vinblastine in dogs with UC where the cancer closely mimics the human condition, clearly justifying further study. The study suggest the potential importance of tracking COX inhibitor use in patients in clinical trials as COX inhibitors could affect treatment response.

Assessment of folate receptor expression and folate uptake in multicentric lymphomas in dogs.

OBJECTIVE: To determine expression of folate receptors (FRs) and folate uptake in multicentric lymphomas in dogs. SAMPLE: 10 dogs with histopathologically confirmed multicentric lymphoma and 20 archival lymph node biopsy specimens from dogs with multicentric lymphoma. PROCEDURES: Multicentric lymphomas in 10 dogs were prospectively evaluated for FR expression by use of immunohistochemical analysis and for in vivo folate uptake by use of nuclear scintigraphy. Dogs with FR-expressing tumors were eligible for FR-targeted chemotherapy. Twenty archival lymphoma biopsy specimens were also evaluated with immunohistochemical analysis. RESULTS: FRs were not detected with immunohistochemical analysis in lymph node samples obtained from the 10 dogs or in archival biopsy specimens. However, nuclear scintigraphy revealed uptake of radioactive tracer in 6 of 10 dogs. Five of these 6 dogs were treated with an FR-targeted chemotherapeutic agent; results of treatment were complete remission in 1 dog, stable disease in 2 dogs, and progressive disease in 2 dogs. Treatment-related toxicoses generally were mild. CONCLUSIONS AND CLINICAL RELEVANCE: This study provided strong evidence for folate uptake in a substantial portion of multicentric lymphomas of dogs and indicated the antitumor activity of FR-targeted chemotherapeutics for these cancers. Use of FR-targeted chemotherapeutics may be promising for the treatment of FR-expressing multicentric lymphomas in dogs. Further studies are needed to determine reasons for lack of immunoreactivity to currently identified anti-FR antibodies and to develop improved methods for detecting FRs in lymphomas of dogs.

Evaluation of two novel self-anchoring barbed sutures in a prophylactic laparoscopic gastropexy compared with intracorporeal tied knots.

OBJECTIVE: To compare laparoscopic gastropexy using 2 self-anchoring barbed sutures to gastropexy using laparoscopically tied intracorporeal knots. STUDY DESIGN: Prospective, randomized controlled, clinical trial. ANIMALS: Dogs (n = 30) weighing >16 kg. METHODS: Dogs were randomly assigned to 1 of 3 laparoscopic gastropexy groups: group 1 (controls), intracorporeal 2-0 polydioxanone sutures (PDSII, Ethicon); group 2, barbed suture (0 Quill™ PDO; Angiotech); and group 3, barbed suture (2-0 V-Loc™ 180; Covidien). Gastropexy suturing time (GST) and total surgery time (TST) were recorded for each dog. Complications were recorded. Each dog was examined by ultrasound (1, 3, and 6 months postoperatively) to ensure persistence of the gastropexy. One dog each in group 2 and group 3 had 2nd look laparoscopy to evaluate the gastropexy. RESULTS: All gastropexies were intact at 6 months. Mean GST was significantly longer for group 1 (36 minutes; range, 25-46 minutes) than for groups 2 (20 minutes; range, 16-37 minutes) and 3 (19 minutes; range, 15-30 minutes; P < .05), which were not significantly different from each other. Likewise TSTs for groups 2 and 3 were significantly shorter than for group 1 (P < .05). CONCLUSION: Barbed sutures (Quill™ and V-Loc™) allowed for effective intracorporeal laparoscopic suturing of an incisional gastropexy without tying intracorporeal knots.

Targeting folate receptors to treat invasive urinary bladder cancer.

Folate receptors (FR) may be of use for targeted delivery of cytotoxic drugs in invasive urothelial carcinoma (iUC), for which improved therapy is needed. FR expression and function in iUC were explored and the antitumor activity and toxicity of a folate-targeted vinblastine conjugate were evaluated in dogs with naturally occurring iUC, an excellent model for human iUC. FR immunohistochemistry was carried out on iUC and normal human and dog bladder tissues together with nuclear scintigraphy in dogs to monitor iUC folate uptake. Dose escalation of a folate-targeted vinblastine compound, EC0905, was conducted in dogs with biopsy-confirmed, FR-positive iUC. FRs were detected by immunohistochemistry (PU17) in most primary iUC and many nodal and lung metastases from dogs, and scintigraphy confirmed folate uptake in both primary and metastatic lesions. The maximum tolerated dose of EC0905 in dogs was 0.25 mg/kg IV weekly, with neutropenia at higher doses. Tumor responses included partial remission (≥ 50% reduction in tumor volume) in five dogs and stable disease (<50% change in tumor volume) in four dogs. Immunoreactivity to PU17 was similar in humans (78% of primary iUC, 80% of nodal metastases). Less immunoreactivity to mab343 (22% of cases) occurred. FR-ß was noted in 21% of human iUC cases. Our findings suggest folate-targeted therapy holds considerable promise for treating iUC, where FR-ß may be important in addition to FR-α.

Accuracy of three-dimensional and two-dimensional ultrasonography for measurement of tumor volume in dogs with transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To determine the accuracy of 3-D and 2-D ultrasonography for quantification of tumor volume in dogs with transitional cell carcinoma (TCC) of the urinary bladder. ANIMALS: 10 dogs with biopsy-confirmed TCC. PROCEDURES: The urinary bladder of each dog was distended with saline (0.9% NaCl) solution (5.0 mL/kg), and masses were measured via 3-D and 2-D ultrasonography. Masses were also measured via 3-D ultrasonography after bladders were distended with 2.5 and 1.0 mL of saline solution/kg. Subsequently, the bladder was deflated and distended with CO(2) (5.0 mL/kg); CT was performed after IV contrast medium administration. Tumor volumes were calculated via 3-D ultrasonography, 2-D ultrasonography, and CT (reference method) and compared via ANOVA, Deming regression, and Bland-Altman plots. Repeated-measures ANOVA was used to assess effects of bladder distension on 3-D tumor volume measurements. Repeatability of measurements was estimated via the coefficient of variation for each method. RESULTS: Repeatability was considered good for all 3 methods. There was no significant difference in tumor volume measurements obtained via 3-D ultrasonography at different degrees of urinary bladder distension. Results of Deming regression and Bland-Altman plots indicated excellent agreement between tumor volume measurement with 3-D ultrasonography and CT, but not between 2-D ultrasonography and CT. CONCLUSIONS AND CLINICAL RELEVANCE: Tumor volume in dogs with TCC of the urinary bladder was accurately measured via 3-D ultrasonography. Use of 3-D ultrasonography can provide a less expensive and more practical method for monitoring response to treatment than CT and was more accurate than 2-D ultrasonography.

Feasibility of computed tomography in awake dogs with traumatic pelvic fracture.

In veterinary medicine, general anesthesia or sedation is generally required to immobilize patients during computed tomography (CT) scanning. This may not be suitable in all patients because of risks of anesthesia. We evaluated the feasibility of pelvic CT examination in 14 awake animals with pelvic trauma. Physical restraint was applied by wrapping the patient in a towel and then taping to the CT table or by directly taping the patient to the CT table. The effect of patient positioning, cooperation on the CT table, preparation time for scanning, scanning time, frequency of repeat scans, image quality, and complications related to physical restraint were evaluated. Fractures were recorded and compared between radiography and CT. Ten of 14 dogs were scanned in lateral recumbency and four in sternal recumbency. All patients were cooperative with the exception of one that moved slightly during the scan. Both physical restraint methods were adequate for CT scanning. Patient preparation took less than 5 min while the scan time was typically less than 1 min. No repeat scans were required in any patient. The transverse CT image quality was good (10/14) or fair (4/14) for interpretation. When comparing the CT images to radiographs, more pelvic fractures were identified with CT than with radiography and a few patients were overdiagnosed based on radiographs. No complications or additional injuries associated with physical restraint were noticed.

Evaluation of experimentally induced injury to the superficial digital flexor tendon in horses by use of low-field magnetic resonance imaging and ultrasonography.

OBJECTIVE: To evaluate tendon injuries in horses over a 16-week period by use of ultrasonography and low-field magnetic resonance imaging (MRI). SAMPLE: Tendons of 8 young adult horses. PROCEDURES: The percentage of experimentally induced tendon injury was evaluated in cross section at the maximal area of injury by use of ultrasonography and MRI at 3, 4, 6, 8, and 16 weeks after collagenase injection. The MRI signal intensities and histologic characteristics of each tendon were determined at the same time points. RESULTS: At 4 weeks after collagenase injection, the area of maximal injury assessed on cross section was similar between ultrasonography and MRI. In lesions of > 4 weeks' duration, ultrasonography underestimated the area of maximal cross-sectional injury by approximately 18%, compared with results for MRI. Signal intensity of lesions on T1-weighted images was the most hyperintense of all the sequences, lesions on short tau inversion recovery images were slightly less hyperintense, and T2-weighted images were the most hypointense. Signal intensity of tendon lesions was significantly higher than the signal intensity for the unaltered deep digital flexor tendon. Histologically, there was a decrease in proteoglycan content, an increase in collagen content, and minimal change in fiber alignment during the 16 weeks of the study. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonography may underestimate the extent of tendon damage in tendons with long-term injury. Low-field MRI provided a more sensitive technique for evaluation of tendon injury and should be considered in horses with tendinitis of > 4 weeks' duration.

Cyclic estrous-like behavior in a spayed cat associated with excessive sex-hormone production by an adrenocortical carcinoma.

A 15-year-old, spayed female domestic shorthair cat was evaluated for 1-year duration of cyclic intermittent estrous behavior. Diagnostic testing performed before referral, including baseline progesterone concentration, human chorionic gonadotropin (hCG) hormone stimulation test and surgical exploratory laparotomy, had remained inconclusive for a remnant ovary. Evaluation of sex hormones before and after adrenocorticotropic hormone (ACTH) administration revealed increased basal concentrations of androstenedione, estradiol, progesterone, and 17α-hydroxyprogesterone and normal ACTH-stimulated hormone concentrations. Enlargement of the right adrenal gland was identified by abdominal ultrasound. The cat underwent an adrenalectomy and histopathology of the excised adrenal gland was consistent with an adrenocortical carcinoma. Clinical signs resolved immediately following surgery, and most hormone concentrations declined to within or below the reference interval (RI) by 2 months after surgery.

Systemic Mycobacterium avium infection in a dog diagnosed by polymerase chain reaction analysis of buffy coat.

Dogs may be infected by Mycobacterium (M.) tuberculosis, M. bovis, and M. avium complex, and the clinical signs associated with each of these infections may be indistinguishable. Rapid speciation of the infecting organism is desirable because of the public health concerns associated with M. bovis and M. tuberculosis infections. A mycobacterial infection was suspected in the dog of this report based on acid-fast staining of organisms in macrophages obtained from liver aspirates and buffy-coat preparations. Polymerase chain reaction (PCR) analysis of a buffy-coat preparation identified M. avium.

Radiographic diagnosis--paraspinal abscess in a dog.

A two-year-old intact male Brittany Spaniel was admitted for evaluation of progressive spinal pain. Previous treatment had been initiated for suspected lumbosacral intervertebral disk disease, however there was poor response to therapy. On presentation the dog was laterally recumbent and neurological examination revealed hyperesthesia over the lumbar vertebral segments. On survey radiography there was loss of detail in the sublumbar fascial planes and inconclusive lumbar vertebra proliferation. Magnetic resonance (MR) imaging was performed to better evaluate the lumbar spine and surrounding tissues, which revealed extensive paralumbar cellulitis, abscessation and osteomyelitis with extradural compression of the spinal cord. MR imaging allowed delineation of the abscessed area, and distinct visualization of its extension into and involvement of the surrounding tissues including muscle, fat, and retroperitoneal structures. In this case, MR imaging was instrumental in defining the extent of the infection and determining whether medical or surgical management of the diseased tissue was necessary. If available, MR may be the imaging method of choice for evaluation of paraspinal abscesses yielding a better insight to the spinal structures involved and facilitating medical or surgical intervention.