Postoperative adjuvant combination therapy with doxorubicin and noncytotoxic suramin in dogs with appendicular osteosarcoma.

Although conventional treatment of dogs with osteosarcoma (OSA) by amputation and chemotherapy results in reported survival times (STs) of 262-413 days, no major improvements in STs have occurred in the past 2 decades. Suramin is a polysulfonated napthylurea, which at noncytotoxic concentrations in vitro, increases tumor sensitivity to chemotherapy, including doxorubicin. The study authors evaluated the combination of noncytotoxic suramin and doxorubicin after amputation in dogs with OSA. The hypothesis was that treatment of dogs with appendicular OSA with amputation, adjuvant doxorubicin, and noncytotoxic suramin would be well tolerated and result in STs at least comparable to those of doxorubicin alone. Forty-seven dogs received 6.75 mg/kg of suramin IV followed by 30 mg/m(2) of doxorubicin IV 4 hr later. Treatment was repeated q 2 wk for five doses. The median disease free time (DFI) was 203 days (range, 42-1,580+ days) and the median ST for all dogs was 369 days (range, 92-1,616+ days). There was no statistical difference in ST and DFI between greyhounds and nonngreyhounds. Adjuvant doxorubicin and noncytotoxic suramin was well tolerated in dogs with OSA following amputation. Additional studies are needed to determine if this combination treatment protocol provides additional clinical benefit compared with doxorubicin alone.

VAC protocol for treatment of dogs with stage III hemangiosarcoma.

Hemangiosarcomas (HSAs) are aggressive tumors with a high rate of metastasis. Clinical stage has been considered a negative prognostic factor for survival. The study authors hypothesized that the median survival time (MST) of dogs with metastatic (stage III) HSA treated with a vincristine, doxorubicin, and cyclophosphamide (VAC) chemotherapy protocol would not be different than those with stage I/II HSA. Sixty-seven dogs with HSA in different anatomic locations were evaluated retrospectively. All dogs received the VAC protocol as an adjuvant to surgery (n = 50), neoadjuvant (n = 3), or as the sole treatment modality (n = 14). There was no significant difference (P = 0.97) between the MST of dogs with stage III and stage I/II HSA. For dogs presenting with splenic HSA alone, there was no significant difference between the MST of dogs with stage III and stage I/II disease (P = 0.12). The overall response rate (complete response [CR] and partial response [PR]) was 86%). No unacceptable toxicities were observed. Dogs with stage III HSA treated with the VAC protocol have a similar prognosis to dogs with stage I/II HSA. Dogs with HSA and evidence of metastases at the time of diagnosis should not be denied treatment.

Current distribution of selected canine vector-borne diseases in domestic dogs from Barranquilla and Puerto Colombia, Atlántico, Colombia.

BACKGROUND: Climate change, the increase of travel with infected animals from endemic areas, the introduction of new vectors in these areas and environmental changes caused by human activity, among other factors, have contributed to the establishment and increase of canine vector-borne diseases (CVBDs), several of which are zoonotic and pose a risk to the human population. In Colombia, there are very few studies that address the prevalence of these diseases. The objective of this study was to update the prevalence of cardiopulmonary dirofilariosis, anaplasmosis, ehrlichiosis and Lyme borreliosis in dogs in Barranquilla and Puerto Colombia, areas of northern Colombia. MATERIALS AND METHODS: The present study included 354 dogs presented to veterinary clinics for routine health examination and foundations for stray dogs between November 2016 and July 2018. RESULTS: The percentage of dogs positive for Ehrlichia spp. was 61.86%, followed by 22.03% for Anaplasma spp., 11.30% positive for Dirofilaria immitis antigens and 0.56% positive for Borrelia burgdorferi. In addition, several dogs positive for antibodies against two or more infectious diseases were found. Higher seroprevalences were documented in outdoor dogs compared to indoor-housed dogs. CONCLUSION: These results suggest that veterinarians should routinely implement prophylactic programmes for these CVBDs, particularly for dogs that reside outdoors.

Paclitaxel gelatin nanoparticles for intravesical bladder cancer therapy.

PURPOSE: We have noted that inadequate drug delivery to tumor cells is a major cause of failed intravesical therapy for nonmuscle invading bladder cancer, partly due to the dilution of drug concentration by urine production during treatment. To address this problem we developed gelatin nanoparticles of paclitaxel designed to yield constant drug concentrations. The hypothesis that a constant, therapeutic concentration in urine, bladder tissue and tumors can be attained was evaluated in dogs. MATERIALS AND METHODS: We studied drug release from paclitaxel gelatin nanoparticles in culture medium in vitro. In vivo studies were performed in tumor-free dogs and in pet dogs with naturally occurring transitional cell carcinoma, in which the pharmacokinetics of paclitaxel gelatin nanoparticles were determined in plasma, urine and tumors. RESULTS: Paclitaxel release from paclitaxel gelatin nanoparticles in vitro and in vivo was rate limited by the drug solubility in aqueous medium. This property yielded constant drug concentrations independent of changes in urine volume during the 2-hour treatment. Intravesical paclitaxel gelatin nanoparticles showed low systemic absorption, and favorable bladder tissue/tumor targeting and retention properties with pharmacologically active concentrations retained in tumors for at least 1 week. CONCLUSIONS: Constant drug release from paclitaxel gelatin nanoparticles may overcome the problem of drug dilution by newly produced urine and the sustained drug levels in tumors may decrease treatment frequency.

Multi-center, placebo-controlled, double-blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision.

PURPOSE: The purpose of this study was to determine the objective response rate (ORR) following treatment of canine mast cell tumors (MCT) with toceranib phosphate (Palladia, SU11654), a kinase inhibitor with both antitumor and antiangiogenic activity through inhibition of KIT, vascular endothelial growth factor receptor 2, and PDGFRbeta. Secondary objectives were to determine biological response rate, time to tumor progression, duration of objective response, health-related quality of life, and safety of Palladia. EXPERIMENTAL DESIGN: Dogs were randomized to receive oral Palladia 3.25 mg/kg or placebo every other day for 6 weeks in the blinded phase. Thereafter, eligible dogs received open-label Palladia. RESULTS: The blinded phase ORR in Palladia-treated dogs (n = 86) was 37.2% (7 complete response, 25 partial response) versus 7.9% (5 partial response) in placebo-treated dogs (n = 63; P = 0.0004). Of 58 dogs that received Palladia following placebo-escape, 41.4% (8 complete response, 16 partial response) experienced objective response. The ORR for all 145 dogs receiving Palladia was 42.8% (21 complete response, 41 partial response); among the 62 responders, the median duration of objective response and time to tumor progression was 12.0 weeks and 18.1 weeks, respectively. Palladia-treated responders scored higher on health-related quality of life versus Palladia-treated nonresponders (P = 0.030). There was no significant difference in the number of dogs with grade 3/4 (of 4) adverse events; adverse events were generally manageable with dose modification and/or supportive care. CONCLUSIONS: Palladia has biological activity against canine MCTs and can be administered on a continuous schedule without need for routine planned treatment breaks. This clinical trial further shows that spontaneous tumors in dogs are good models to evaluate therapeutic index of targeted therapeutics in a clinical setting.

Evaluation of a point-of-care hematology analyzer for use in dogs and cats receiving chemotherapeutic treatment.

OBJECTIVE: To compare WBC, neutrophil, and platelet counts and Hct values obtained with a point-of-care hematology analyzer with values obtained by a reference method for dogs and cats receiving chemotherapy. DESIGN: Cross-sectional study. ANIMALS: 105 dogs and 25 cats undergoing chemotherapy. PROCEDURES: Blood samples were analyzed with a point-of-care hematology analyzer and with an impedance- and laser-based analyzer with manual differential WBC counts. Results for WBC, neutrophil, and platelet counts and Hct were compared. Sensitivity and specificity of the point-of-care analyzer to detect leukopenia, neutropenia, and anemia were calculated. RESULTS: 554 canine and 96 feline blood samples were evaluated. Correlation coefficients for dogs and cats, respectively, were 0.92 and 0.95 for total WBC count, 0.91 and 0.88 for neutrophil count, 0.95 and 0.92 for Hct, and 0.93 and 0.71 for platelet count. Sensitivity and specificity, respectively, of the point-of-care analyzer to detect leukopenia were 100% and 75% for dogs and 100% and 68% for cats; to detect neutropenia were 80% and 97% for dogs and 100% and 80% for cats; to detect anemia were 100% and 80% for dogs and 100% and 66% for cats; and to detect thrombocytopenia were 86% and 95% for dogs and 50% and 87% for cats. CONCLUSIONS AND CLINICAL RELEVANCE: The point-of-care analyzer was reliable for monitoring CBCs of dogs and cats receiving chemotherapy. It had good to excellent correlation for WBC and neutrophil counts and Hct and accurately detected leukopenia, neutropenia, and anemia. Sensitivity of the analyzer for detecting thrombocytopenia was lower but acceptable.

Results of excision of thymoma in cats and dogs: 20 cases (1984-2005).

OBJECTIVE: To provide long-term follow-up information for a series of dogs and cats with invasive and noninvasive thymomas treated by excision alone. DESIGN: Retrospective case series. ANIMALS: 9 cats and 11 dogs with thymoma. PROCEDURES: Medical records were reviewed. The following factors were analyzed for their effect on prognosis: age of dog or cat, invasiveness of the tumor, percentage of lymphocytes in the mass (percentage lymphocyte composition) on histologic evaluation, and mitotic index of the mass. RESULTS: All patients were treated with excision of the tumor alone. Median overall survival time for the cats was 1,825 days, with a 1-year survival rate of 89% and a 3-year survival rate of 74%. Median overall survival time for the dogs was 790 days, with a 1-year survival rate of 64% and a 3-year survival rate of 42%. Recurrence of thymoma was observed in 2 cats and 1 dog, and a second surgery was performed in each, with subsequent survival times of 5, 3, and 4 years following the first surgery. Percentage lymphocyte composition of the mass was the only factor that was significantly correlated with survival time; animals with a high percentage of lymphocytes lived longer. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study indicated that most cats and dogs with thymomas did well after excision. Even cats and dogs with invasive masses that survived the surgery and the few cats and dogs with recurrent thymomas or paraneoplastic syndromes had a good long-term outcome. Excision should be considered an effective treatment option for dogs and cats with thymomas.

Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B.

BACKGROUND: Canine osteosarcoma is clinically nearly identical to the human disease, but is common and highly heritable, making genetic dissection feasible. RESULTS: Through genome-wide association analyses in three breeds (greyhounds, Rottweilers, and Irish wolfhounds), we identify 33 inherited risk loci explaining 55% to 85% of phenotype variance in each breed. The greyhound locus exhibiting the strongest association, located 150 kilobases upstream of the genes CDKN2A/B, is also the most rearranged locus in canine osteosarcoma tumors. The top germline candidate variant is found at a >90% frequency in Rottweilers and Irish wolfhounds, and alters an evolutionarily constrained element that we show has strong enhancer activity in human osteosarcoma cells. In all three breeds, osteosarcoma-associated loci and regions of reduced heterozygosity are enriched for genes in pathways connected to bone differentiation and growth. Several pathways, including one of genes regulated by miR124, are also enriched for somatic copy-number changes in tumors. CONCLUSIONS: Mapping a complex cancer in multiple dog breeds reveals a polygenic spectrum of germline risk factors pointing to specific pathways as drivers of disease.

Hemostatic abnormalities in dogs with carcinoma: a thromboelastographic characterization of hypercoagulability.

Hemostatic abnormalities were investigated in 32 dogs with carcinoma and 19 age-matched healthy dogs. Thromboelastography, hemostasis profile (i.e. prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen concentration), platelet count (PLT), thrombin-antithrombin complexes (TAT), and plasminogen activator inhibitor-1 (PAI-1) activity were evaluated. Dogs with carcinomas had faster thrombus generation (TEG(TG), a mathematic value obtained from the first derivate of the thromboelastographic tracing; 834.8±91.1 vs. 707.8±75.8mm/min; mean±SD), increased fibrinogen concentration (276 vs. 151mg/dL), and PLT (425 vs. 324U×10(9)/L), but had decreased PAI-1 activity (15.7 vs. 26.2IU/mL).The most common hemostatic abnormalities found in carcinoma dogs were hypercoagulability (TEG(TG)>mean+2 SD of healthy dogs) and thrombocytosis (PLT>424×10(9)U/L) in 46% of cases, and hyperfibrinogenemia (fibrinogen >384mg/dL) in 32% of cases. Disseminated intravascular coagulation was uncommon and the extent of disease was not correlated with hypercoagulability. TEG(TG) showed good correlation with fibrinogen (r=0.80) and hyperfibrinogenemia seems to be a main factor of the hypercoagulable state in carcinoma dogs. In conclusion, TEG(TG) is a valid parameter to diagnose hypercoagulability.

Use of transsplenic injection of agitated saline and heparinized blood for the ultrasonographic diagnosis of macroscopic portosystemic shunts in dogs.

We describe the use of ultrasonography-guided percutaneous splenic injection of agitated saline and heparinized blood for the diagnosis of portosystemic shunts (PSS) in 34 dogs. Agitated saline mixed with 1 ml of heparinized autologous blood was injected into the spleen of 34 sedated dogs under sonographic guidance. The transducer was then sequentially repositioned to visualize the portal vein, the caudal vena cava, and the right atrium through different acoustic windows. It was possible to differentiate between intrahepatic and extrahepatic shunts depending on the entry point of the microbubbles into the caudal vena cava. Portoazygos shunts and portocaval shunts could be differentiated based on the presence of microbubbles in the caudal vena cava and/or the right atrium. In one dog, collateral circulation due to portal hypertension was identified. In dogs with a single extrahepatic shunt, the microbubbles helped identify the shunting vessel. The technique was also used postoperatively to assess the efficacy of shunt closure. All abnormal vessels were confirmed by exploratory laparotomy or with ultrasonographic identification of the shunting vessel. Ultrasound-guided transsplenic injection of agitated saline with heparinized blood should be considered as a valuable technique for the diagnosis of PSS; it is easy to perform, safe, and the results are easily reproducible.

The nitroblue tetrazolium reduction test in canine leishmaniasis.

The nitroblue tetrazolium reduction test (NBT) is a quick, easy and cheap assay based on the activation percentage of neutrophils in peripheral blood. The aim of this study was to evaluate the NBT on healthy dogs and in dogs affected by different degrees of leishmaniasis (Stages I and IV). Forty healthy dogs, 20 dogs in Stage I and 20 dogs in Stage IV were included in the study. Three millilitres of blood were extracted from all the dogs via jugular venipuncture in tubes with EDTA. Incubation with NBT was performed depositing 0.05 ml of the leukocyte suspension in the same quantity of 0.1% concentration NBT. The results of the test were reported as NBT reduction rate which represents the percentage of the total of neutrophils evaluated that presented cytoplasmatic accumulations of formazan, meaning a positive NBT reduction. The mean NBT reduction rate for the healthy dogs group was 4.57%, 34% for Stage I dogs (mild disease) and 3.7% for dogs in Stage IV (severe disease), showing that dogs affected with leishmaniasis but with no clinical development of disease have a significantly higher neutrophil reactivity (p<0.01). Although more studies evaluating the correlation of NBT with other tests prior to and during treatment are needed, NBT could be a good assay in canine leishmaniasis evaluation.

Pathologic correlation of resistive and pulsatility indices in canine abdominal lymph nodes.

We assessed the ability of the resistive index (RI) and pulsatility index (PI) to allow differentiation between normal, reactive, and neoplastic lymph nodes. Forty-seven medial iliac and 54 mesenteric lymph nodes from 83 dogs were evaluated sonographically. A cytologic sample was obtained in each dog that allowed categorization into one of the categories defined above. We found a significant difference in the RI and PI in nonneoplastic vs. neoplastic medial iliac and mesenteric lymph nodes. Values higher than 0.67 for the RI and 1.02 for the PI in medial iliac lymph nodes and higher than 0.76 for the RI and 1.23 for the PI in mesenteric lymph nodes had a high sensitivity and specificity for differentiating benign from neoplastic lymph nodes.

Estudio anatomoclínico del cáncer del páncreas: presentación de 30 pacientes / Anatomoclinical study of the cancer of the pancreas: presentation of 30 patients

Presentamos un estudio anatomoclínico de 30 pacientes con el diagnóstico de cáncer pancreático comprobado con la necropsia en los hospitales "Joaquín Castillo Duany", "Saturnino Lora" y "Conrado Benítez" seleccionados por un muestreo aleatorio simple. Recogimos en cada paciente los datos de identidad personal, antecedentes patológicos personales, los síntomas y signos, así como la localización del cáncer en la víscera y el tipo histológico. Los resultados fueron tabulados y procesados mediante la media aritmética, la desviación estándar y la prueba de chi-cuadrado. Encontramos que la edad promedio fue de 64 años, con 63,3 % perteneciente al sexo masculino y los factores de riesgo fueron: tabaquismo, alcoholismo, diabetes mellitus y pancreatitis crónica. La tríada sintomática más freceunete fue: astenia, anorexia y dolor abdominal, mientras que la tríada signológica más común fue: hepatomegalia, ictericia y tumor palpable. La localización más frecuente fue en la cabeza, seguida del cuerpo y la cola. En todos se halló adenocarcinoma primitivo del páncreas