A pilot study of toceranib/vinblastine therapy for canine transitional cell carcinoma.

BACKGROUND: Effective therapies for transitional cell carcinoma (TCC) are limited, with objective response rates to most chemotherapeutic regimens below 20%. The purpose of this study was to investigate the biologic activity of combined toceranib phosphate and vinblastine chemotherapy for treatment of TCC. A secondary objective was to compare the utility of Computed Tomography (CT) and abdominal ultrasound (AUS) in tumor response assessments. RESULTS: Dogs with TCC received vinblastine at 1.6 mg/m2 every 2 weeks and toceranib at 2.5-2.75 mg/kg on Monday/Wednesday/Friday. Tumor monitoring was achieved through CT and AUS. Five patients completed the 16-week study. Based on AUS assessments, 3 dogs experienced biologic response to therapy including partial responses (PR, n = 2) and stable disease (SD, n = 1). Based on CT, 5 dogs experienced a biologic response (n = 2 PR, n = 3 SD). Both imaging modalities (ultrasound and CT) were found to provide repeatable measurements between operators, however agreement between operator measurements was greater when CT images were used to assess tumor size. CONCLUSIONS: The combination of toceranib and vinblastine did not result in improved response rates. While agreement in tumor volume assessments between both AUS and CT were excellent between operators, this did not extend to assessment of tumor response. The higher rate of concordance between operators when assessing response to treatment with CT suggests that CT should be considered for future clinical trials involving canine bladder TCC to improve the accuracy and repeatability of tumor measurement. The data suggest that response to therapy as assessed by AUS or CT do not predict duration of clinical response.

Ionized hypercalcemia can resolve with nutritional modification in cats with idiopathic hypercalcemia or chronic kidney disease.

CASE SERIES SUMMARY: Cats with ionized hypercalcemia that were fed diets with either more than 200 mg calcium per 100 kilocalories (kcal), a calcium:phosphorus (Ca:P) ratio greater than 1.4:1 or both, based on diet history, were included in this case series. Ionized hypercalcemia was documented at least twice in all cats before enrollment. Cats were referred for evaluation of ionized hypercalcemia (n = 5) or were incidentally found to have ionized hypercalcemia (n = 5). After medical workups, cats were diagnosed with either idiopathic hypercalcemia (IHC; n = 7) or chronic kidney disease (n = 3). Cats receiving medications to treat IHC (eg, alendronate, corticosteroids) were excluded. Nutritional recommendations were made to transition the cats to diets with less thn 200 mg calcium per 100 kcal and a Ca:P ratio less than 1.4:1. Ionized calcium (iCa) concentrations were rechecked in all cats, with a median recheck time of 9 weeks (range 3-20). Of the 10 cats, nine (90%) had a decrease in iCa. Of the 10 cats, six (60%) became normocalcemic after the diet change, three (30%) had a partial response and one (10%) did not respond. Of the four cats that did not achieve normocalcemia with a change in diet, two (50%) received chia seeds (1-2 g per day), and at the next recheck, both cats' iCa concentrations had normalized. Three cats had a long-term follow-up. Ionized normocalcemia was maintained for at least two consecutive follow-up visits over a median follow-up period of 33 weeks (range 12-34). RELEVANCE AND NOVEL INFORMATION: Dietary calcium concentrations and the dietary Ca:P ratio appear to be important variables in considering nutritional approaches for hypercalcemic cats.

Outcome after placement of an artificial urethral sphincter in 27 dogs.

OBJECTIVE: To evaluate the safety and efficacy of an adjustable artificial urethral sphincter (AUS) in a population of dogs with acquired or congenital urinary incontinence. STUDY DESIGN: Case series. ANIMALS: Dogs (n = 27) with naturally occurring urinary incontinence. METHODS: Medical records (January 2009-July 2011) of dogs that had AUS implantation for treatment of urinary incontinence were reviewed and owners were interviewed by telephone to assess outcome. Continence was scored using a previously established analogue scale, with 1 representing constant leakage and 10 representing complete continence. RESULTS: Twenty-four female and 3 male dogs had AUS implantation. Causes of incontinence included urethral sphincter mechanism incompetence (n = 18), continued incontinence after ectopic ureter repair (6), and pelvic bladder (3). Medical therapy was unsuccessful in 25 dogs before AUS implantation. Surgery was performed without major complications in 25 dogs; 2 developed partial urethral obstruction after 5 and 9 months. Median (interquartile range) follow-up for the other 25 dogs was 12.5 (6-19) months. Continence scores were significantly improved (P < .0001) between the preoperative period (2 [1-4]) and last follow-up (9 [8-10]). Overall, 22 owners described themselves as very satisfied, 2 as satisfied, and 3 as unsatisfied. CONCLUSIONS: AUS implantation was successful in restoring continence in male and female dogs with both congenital and acquired urinary incontinence. Dogs that develop partial urethral obstruction may require AUS removal.

Ectopic ureters in male dogs: review of 16 clinical cases (1999-2007).

Ureteral ectopia is a well-described cause of urinary incontinence in female dogs, but this condition has not been completely characterized in male dogs. Sixteen male dogs with ectopic ureters were evaluated between Jan 1999 and Mar 2007. Male dogs were similar to female dogs with ectopic ureters in terms of breed, presenting complaint, age of onset, and bilateral nature of the ectopia. Diagnosis was made by expert interpretation of imaging techniques such as excretory urography and contrast-enhanced computed tomography (CT). Overall, 11 of 13 dogs that had surgical correction of ectopic ureters were incontinent preoperatively. Urinary continence was restored in 82% of those dogs.

An early prediction model for canine chronic kidney disease based on routine clinical laboratory tests.

The aim of this study was to derive a model to predict the risk of dogs developing chronic kidney disease (CKD) using data from electronic health records (EHR) collected during routine veterinary practice. Data from 57,402 dogs were included in the study. Two thirds of the EHRs were used to build the model, which included feature selection and identification of the optimal neural network type and architecture. The remaining unseen EHRs were used to evaluate model performance. The final model was a recurrent neural network with 6 features (creatinine, blood urea nitrogen, urine specific gravity, urine protein, weight, age). Identifying CKD at the time of diagnosis, the model displayed a sensitivity of 91.4% and a specificity of 97.2%. When predicting future risk of CKD, model sensitivity was 68.8% at 1 year, and 44.8% 2 years before diagnosis. Positive predictive value (PPV) varied between 15 and 23% and was influenced by the age of the patient, while the negative predictive value remained above 99% under all tested conditions. While the modest PPV limits its use as a stand-alone diagnostic screening tool, high specificity and NPV make the model particularly effective at identifying patients that will not go on to develop CKD.

Cutaneous and systemic blastomycosis, hypercalcemia, and excess synthesis of calcitriol in a domestic shorthair cat.

A 9 yr old domestic shorthair cat was diagnosed with cutaneous and pulmonic blastomycosis. Severe persistent ionized hypercalcemia and excess circulating concentration of calcitriol were documented in association with blastomycosis. Ionized hypercalcemia resolved when the granulomatous lesions of blastomycosis resolved and the calcitriol levels decreased.

Diagnosis and management of ureteroceles in two female dogs.

Two intact female dogs were examined for refractory pollakiuria and stranguria. One of these two dogs also exhibited urinary incontinence. Ectopic ureteroceles were diagnosed via ultrasonography and cystoscopy in both dogs. Both dogs were taken to surgery for ureterocele resection and neoureterostomy, resulting in complete resolution of clinical signs. Although uncommonly reported in the veterinary literature, ectopic ureteroceles can be associated with recurrent lower urinary tract infection with and without urinary incontinence. With a correct diagnosis and appropriate treatment, prognosis for ectopic ureteroceles can be good provided there is not a concurrent significant loss of renal function.

Interobserver reliability of canine urine specific gravity assessed by analog or digital refractometers.

Refractometry is utilized routinely to evaluate canine urine specific gravity (USG) in veterinary clinical settings. We aimed to determine if the magnitude of interobserver reliability when assessing canine USG via refractometry could impact clinical judgment. USG was determined in 38 dogs by 3 registered veterinary technicians (RVTs) using both an optical analog refractometer and a digital refractometer. Summary statistics were reported, interobserver reliability was assessed via intraclass correlation coefficient (ICC) analysis through a 2-way mixed-effects model, and agreement between RVT pairs was compared through Bland-Altman plots. The median analog refractometer USG measurement was 1.018 (range: 1.004-1.040) and for the digital refractometer was 1.0176 (1.0035-1.0357). The analog refractometer average measure ICC was 0.995 (95% CI: 0.992, 0.997; p < 0.001). The digital refractometer average measure ICC was 0.999 (95% CI: 0.999, 1.000; p < 0.001). Strong agreement between all pairs of RVTs was seen via Bland-Altman plots for both analog and digital refractometers, with 95% CIs spanning no more than 0.002 in either the positive or negative direction for all pairings. The interobserver variability in canine USG measurements by RVTs was trivial and did not impact clinical judgment and decision-making.

Short-term efficacy of epidural pain management in dogs undergoing cystoscopy.

BACKGROUND: The effects of epidural anesthesia in dogs undergoing cystoscopy are unknown. OBJECTIVE: To investigate the effect of epidural analgesia on postcystoscopy pain in dogs. ANIMALS: Twenty-six dogs undergoing routine cystoscopy for lower urinary tract disease. METHODS: Prospective, randomized, blinded observational study. Dogs were assigned either to a treatment group that received epidural anesthesia (preservative free morphine sulfate, 0.09 mg/kg; 1% ropivacaine, 0.2 mg/kg; total volume delivered, 1 mL/4.5 kg of body weight to a maximum of 10 mL; n = 9) or to a nonepidural control group (n = 13). Vital signs were monitored for 24 hours, and sedation and pain scores, behavioral assessments, and presence or absence of complications was evaluated for 5 days postprocedure. RESULTS: All dogs tolerated the epidural without complications. Four dogs were removed from the study because of status unblinding, lack of patient cooperation, or incomplete follow-up. No significant differences were noted in postprocedural pain scores in dogs that received epidural analgesia. Significant differences in postprocedural pain scores were noted in the nonepidural control group. No significant differences were noted in vital signs, behavioral assessments, or the proportion of dogs with a 50% increase in pain scores between the epidural and nonepidural groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Epidural anesthesia was well-tolerated. Dogs not receiving the epidural had poor postprocedural pain control. A consistent benefit for the epidural vs nonepidural group could not be identified. Additional studies are required to better assess the impact and efficacy of epidural anesthesia for cystoscopic procedures.

A protocol for managing urethral obstruction in male cats without urethral catheterization.

OBJECTIVE: To determine efficacy of a protocol for managing urethral obstruction (UO) in male cats without urethral catheterization. DESIGN: Clinical trial. ANIMALS: 15 male cats with UO in which conventional treatment had been declined. PROCEDURES: Laboratory testing and abdominal radiography were performed, and cats with severe metabolic derangements or urinary calculi were excluded. Treatment included administration of acepromazine (0.25 mg, IM, or 2.5 mg, PO, q 8 h), buprenorphine (0.075 mg, PO, q 8 h), and medetomidine (0.1 mg, IM, q 24 h) and decompressive cystocentesis and SC administration of fluids as needed. Cats were placed in a quiet, dark environment to minimize stress. Treatment success was defined as spontaneous urination within 72 hours and subsequent discharge from the hospital. RESULTS: Treatment was successful in 11 of the 15 cats. In the remaining 4 cats, treatment was considered to have failed because of development of uroabdomen (n=3) or hemoabdomen (1). Cats in which treatment failed had significantly higher serum creatinine concentrations than did cats in which treatment was successful. Necropsy was performed on 3 cats in which treatment had failed. All 3 had severe inflammatory disease of the urinary bladder, but none had evidence of bladder rupture. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in male cats, a combination of pharmacological treatment, decompressive cystocentesis, and a low-stress environment may allow for resolution of UO without the need for urethral catheterization. This low-cost protocol could serve as an alternative to euthanasia when financial constraints prevent more extensive treatment.

Surgical management of diffuse polypoid cystitis using submucosal resection in a dog.

A 6-year-old, spayed female Labrador retriever was presented with clinical signs of stranguria, pollakiuria, and hematuria of 12 weeks' duration. A bacterial urinary tract infection, diffuse polypoid cystitis, and emphysematous cystitis were diagnosed. Antibiotic therapy combined with extensive resection of the mucosa and submucosa associated with polypoid lesions resulted in complete resolution of clinical signs and resolution of the remaining polypoid lesions. Polypoid cystitis is an uncommon but clinically relevant and reversible condition of the urinary bladder. Resection of mucosa and submucosa of the urinary bladder in dogs with polypoid cystitis may be a useful surgical treatment and can be considered as an alternative to partial cystectomy or mucosal resection.

Association of abdominal effusion with a single decompressive cystocentesis prior to catheterization in male cats with urethral obstruction.

OBJECTIVE: To evaluate the occurrence of abdominal effusion and its association with decompressive cystocentesis in male cats with urethral obstruction. DESIGN: Prospective observational clinical study. ANIMALS: Forty-five male neutered, client-owned cats with naturally occurring urethral obstruction. PROCEDURES: Laboratory testing and point-of-care ultrasonography were performed. Presence of abdominal effusion was evaluated using the Focused Assessment with Sonography for Trauma (FAST) technique at presentation. Decompressive cystocentesis was then performed prior to catheterization by a standardized technique. Repeat FAST examination was performed 15 minutes after cystocentesis and the following day to further assess for the presence of abdominal effusion. RESULTS: A mean volume of 92.3 ± 35.2 mL of urine was removed from each cat via cystocentesis prior to catheterization. At presentation, 15 of 45 (33%) had abdominal effusion (13/15 with scant effusion, 2/15 with mild), with an additional 7 cats developing scant effusion 15 minutes post-cystocentesis. By the following day, 4 cats still had scant effusion present. No significant complications secondary to cystocentesis were reported. No association was found between severity of azotemia, or volume removed by cystocentesis, and the presence of effusion at presentation or after decompressive cystocentesis was performed. CONCLUSIONS AND CLINICAL RELEVANCE: A single decompressive cystocentesis prior to catheterization did not lead to development of clinically significant abdominal effusion or other discernable complications and appears to be a safe procedure in this population of patients. Abdominal effusion may be found at presentation in cats with urethral obstruction. The significance of this effusion remains to be determined.

Effects of calcifediol supplementation on markers of chronic kidney disease-mineral and bone disorder in dogs with chronic kidney disease.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) in dogs is associated with hypovitaminosis D, increased parathyroid hormone (PTH), and increased fibroblast growth factor-23 (FGF-23) concentrations. Best practice for vitamin D metabolite supplementation in CKD-MBD remains unknown. OBJECTIVE: To provide an extended-release calcifediol supplement to dogs with CKD and to measure its effects on variables indicative of CKD-MBD. ANIMALS: Ten dogs with International Renal Interest Society stages 2 and 3 CKD. METHODS: In a prospective study, dogs received a calcifediol supplement for 84 days. Serum 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2 D), 24,25-dihydroxyvitamin D (24,25[OH]2 D), creatinine, calcium, phosphorus, PTH, plasma FGF-23 concentrations, and urine profiles were measured monthly during supplementation. Urine calcium to creatinine (UCa/Cr) ratios and fractional excretion of calcium, phosphorus, and sodium were determined. RESULTS: All serum vitamin D metabolite concentrations increased significantly by day 84 (P < .001): [25(OH)D (median 249.9 ng/mL; range, 149.7-469.9 ng/mL) compared to baseline (median 50.2 ng/mL; range, 31.3-66.0 ng/mL); 1,25(OH)2 D (median 66.1 pg/mL; range, 56.9-88.1 pg/mL) compared to baseline (median 37.3 pg/mL; range, 29.3-56.7 pg/mL); 24,25(OH)2 D (median 81.4 ng/mL; range, 22.1-151.7 ng/mL) compared to baseline (median 15.4 ng/mL; range, 6.9-40.6 ng/mL)]. There were no significant differences in calcium, phosphorus, PTH concentrations, UCa/Cr or fractional excretion of calcium. No dog developed ionized hypercalcemia. Plasma FGF-23 concentrations increased by day 84 (median 1219 pg/mL; range, 229-8824 pg/mL) compared to baseline (median 798 pg/mL; range, 103-4.145 pg/mL) (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Calcifediol supplementation for 84 days was well-tolerated in dogs with IRIS stages 2 and 3 CKD. It remains to be determined how long-term supplementation would affect CKD progression and QOL.

Determination of a serum total calcium concentration threshold for accurate prediction of ionized hypercalcemia in dogs with and without hyperphosphatemia.

BACKGROUND: Total serum calcium (tCa) concentrations are poorly predictive of ionized calcium (iCa) status in dogs. HYPOTHESIS: There is an optimal threshold of tCa concentration that is highly predictive of ionized hypercalcemia and this threshold is higher in hyperphosphatemic dogs as compared to nonhyperphosphatemic dogs. ANIMALS: Nonhyperphosphatemic (n = 1593) and hyperphosphatemic (n = 250) adult dogs. METHODS: Retrospective medical record review of paired tCa and iCa concentration measurements in dogs presented to a university teaching hospital over a 5-year period. Positive and negative predictive values, sensitivity, and specificity were calculated for tCa concentration thresholds of 11.0-15.0 mg/dL (upper limit of laboratory reference interval = 11.5 mg/dL) in nonhyperphosphatemic and hyperphosphatemic groups. RESULTS: In nonhyperphosphatemic dogs, an optimal tCa concentration threshold of 12.0 mg/dL resulted in a positive predictive value of 93% (95% confidence interval [CI], 84%-98%) and sensitivity of 52% (95% CI, 43%-61%) for ionized hypercalcemia. An optimal tCa concentration threshold was not identified for hyperphosphatemic dogs. The nonhyperphosphatemic dogs had a higher prevalence of ionized hypercalcemia than the hyperphosphatemic dogs (7 versus 3%, P = .04) and a lower prevalence of ionized hypocalcemia (23 versus 62%, respectively; P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: High tCa concentrations are strongly predictive of ionized hypercalcemia in nonhyperphosphatemic adult dogs and should prompt further diagnostic testing to determine the underlying cause of hypercalcemia. In this population, dogs without increased tCa concentrations rarely had ionized hypercalcemia, but iCa concentrations still should be evaluated in patients with tCa concentrations within the reference interval if there is clinical suspicion for calcium abnormalities.

Association between vitamin D metabolites, vitamin D binding protein, and proteinuria in dogs.

BACKGROUND: Proteinuria has been associated with progression of renal disease and increased morbidity and mortality in dogs and people. In people, proteinuria also has been associated with hypovitaminosis D. Little is known about the relationship between vitamin D metabolism and proteinuria in dogs. OBJECTIVES: To further elucidate vitamin D status in dogs with protein-losing nephropathy (PLN) and minimal to no azotemia. We hypothesized that vitamin D metabolites would be lower in dogs with PLN compared to healthy dogs. ANIMALS: Twenty-three client-owned adult dogs with PLN and 10 healthy control dogs. METHODS: Serum 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2 D), 24,25-dihydroxyvitamin D (24,25[OH]2 D), serum vitamin D binding protein (VDBP), and urine 25(OH)D concentrations were measured. RESULTS: Compared to healthy dogs, dogs with PLN had lower concentrations of all vitamin D metabolites (P < .01). Correlations (rho; 95% confidence interval [CI]) in dogs with PLN are reported. Serum 25(OH)D and 24,25(OH)2 D concentrations were positively correlated with albumin (r = 0.47; 0.07-0.74), and 24,25(OH)2 D was negatively correlated with urine protein-to-creatinine ratio (UPC; r = -0.54; -0.78 to -0.16). Urine 25(OH)D-to-creatinine ratio was negatively correlated with serum albumin concentration (r = -0.77; -0.91 to -0.50) and positively correlated with UPC (r = 0.79; 0.53-0.91). Serum VDBP concentration was positively correlated with serum albumin concentration (r = 0.53; 0.05-0.81). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with PLN have decreased serum concentrations of vitamin D metabolites. Urine 25(OH)D-to-creatinine ratio and UPC are correlated in PLN dogs. Future studies are needed to assess additional management strategies for dogs with PLN.

Medication-related osteonecrosis of the jaw after long-term bisphosphonate treatment in a cat.

A 12-year-old, neutered female, domestic medium hair cat was evaluated for a nonhealing, oral mucosal ulceration. The cat had a history of idiopathic hypercalcemia that had been treated with a bisphosphonate for 41 months. Oral examination identified exposed maxillary bone adjacent to a previous extraction site. Histopathology of the exposed bone and associated mucosa was most consistent with medication-related osteonecrosis of the jaw. Treatment involved both medical and surgical interventions. Oral mucosal healing occurred after 6 months of treatment.

Vitamin D metabolism in dogs with and without hypercalciuric calcium oxalate urolithiasis.

BACKGROUND: There are abnormalities in vitamin D metabolism in people with calcium nephrolithiasis, but limited data are available on vitamin D status in dogs with calcium oxalate (CaOx) urolithiasis. OBJECTIVE: To compare serum concentrations of vitamin D metabolites in dogs with and without hypercalciuric CaOx urolithiasis. ANIMALS: Thirty-eight dogs with (n = 19) and without (n = 19) a history of CaOx urolithiasis and hypercalciuria. METHODS: Retrospective cross-sectional study. Serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2 D], and 24,25-dihydroxyvitamin D [24,25(OH)2 D] were measured. The ratios of 25(OH)D/24,25(OH)2 D and 1,25(OH)2 D/25(OH)D were compared between cases and controls. RESULTS: There were no significant differences between cases and controls when comparing 25(OH)D, 24,25(OH)2 D, 1,25(OH)2 D, or 1,25(OH)2 D/25(OH)D. Cases had higher 25(OH)D/24,25(OH)2 D (median = 1.40, range = 0.98-1.58) compared to controls (median = 1.16, range = 0.92-2.75; P = .01). There was overlap in the ranges for 25(OH)D/24,25(OH)2 D between cases and controls, but 6 cases (32%) had ratios above the control dog range. There was a moderate positive correlation between the ratio of 25(OH)D/24,25(OH)2 D and urinary calcium-to-creatinine ratios (r = 0.40, 95% confidence interval = 0.10-0.64; P = .01). CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that decreased conversion of 25(OH)D to 24,25(OH)2 D occurs in a subset of dogs with CaOx urolithiasis. Abnormalities in vitamin D metabolism might contribute to stone risk in dogs.

Incidence of bacteriuria at presentation and resulting from urinary catheterization in feline urethral obstruction.

OBJECTIVE: To determine the incidence of bacteriuria at the time of presentation and as a result of indwelling urethral catheterization in naturally occurring feline urethral obstruction (UO). DESIGN: Prospective observational study. SETTING: University teaching hospital. ANIMALS: A population of 34 male cats with UO admitted for standard medical care. INTERVENTIONS: A presenting urine sample was obtained by cystocentesis (precatheterization). After catheterization (performed under strict aseptic technique), a urine sample was obtained through the urinary catheter every 24 hours, as well as just prior to catheter removal. Urine was applied to culture media within 30 minutes of collection or refrigerated immediately at 4°C for subsequent culture the following morning. Samples positive for growth (defined as > 104 colony forming units/mL) had bacterial identification and susceptibility testing performed. MEASUREMENTS AND MAIN RESULTS: All 34 cats enrolled had initial culture performed. Of these, 1 patient died and 2 were euthanized within 24 hours and therefore subsequent cultures were obtained. The remaining 31 cats had median catheterization time of 42 hours (range 20-110 hours). No urine cultures yielded growth at presentation (0/34). A total of 4 of 31 patients (13%) subsequently had bacterial cultures that yielded growth. In these cases, all yielded growth by the 24-hour time point, and all had the same organism identified on subsequent cultures. Identified bacteria included Streptococcus spp. (3) and Pasteurella spp. (1). CONCLUSIONS: The male cats with UO in this study did not have bacteriuria at the time of presentation. The overall incidence of acquired bacteriuria was found to be 13% and could represent a transient bacterial population or true bacterial urinary tract infection. Based on these findings, empirical administration of antibiotics is not warranted in male cats with UO.