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1.
Int J Parasitol Drugs Drug Resist ; 24: 100520, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38237210

RESUMO

Surveillance data for Ancylostoma spp. and the A. caninum benzimidazole treatment resistance associated F167Y polymorphism using molecular diagnostics was obtained in a large population of dogs from the United States and Canada. Real-time PCR (qPCR) for Ancylostoma spp. and allele-specific qPCR detecting a single nucleotide polymorphism (SNP) F167Y was used in 262,872 canine stool samples collected between March and December of 2022. Ancylostoma spp. was found at an overall prevalence of 2.5% (6538/262,872), with the highest prevalence in the Southern US, 4.4% (4490/103,095), and the lowest prevalence in Canada 0.6% (101/15,829). The A. caninum F167Y polymorphism was found with the highest prevalence (13.4%, n = 46/343) in the Western US and the lowest in Canada at 4.1% (4/97). The F167Y polymorphism was detected every month over the 10-month collection period. Seasonal distribution showed a peak in June for both Ancylostoma spp. (3.08%, 547/17,775) and A. caninum F167Y (12.25%, 67/547). However, the A. caninum F167Y polymorphism prevalence was highest in September (13.9%, 119/856). Age analysis indicates a higher prevalence of both hookworm infections and occurrence of resistant isolates in puppies. The breeds with the highest F167Y polymorphism prevalence in Ancylostoma spp. detected samples were poodles (28.9%), followed by Bernese Mountain dogs (25%), Cocker spaniels (23.1%), and greyhounds (22.4%). Our data set describes widespread geographic distribution of the A. caninum benzimidazole resistance associated F167Y polymorphism in the United States and Canada, with no clear seasonality compared to the Ancylostoma spp. prevalence patterns. The F167 polymorphism was present in all geographic areas with detected hookworms, including Canada. Our study highlights that the F167Y polymorphism is represented in many dog breeds, including greyhounds.


Assuntos
Ancylostoma , Doenças do Cão , Cães , Animais , Estados Unidos/epidemiologia , Ancylostoma/genética , Ancylostomatoidea/genética , Estações do Ano , Doenças do Cão/epidemiologia , Fezes , Benzimidazóis
2.
Vet Immunol Immunopathol ; 267: 110691, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056066

RESUMO

Preventative anti-cancer vaccination strategies have long been hampered by the challenge of targeting the diverse array of potential tumor antigens, with successes to date limited to cancers with viral etiologies. Identification and vaccination against frameshift neoantigens conserved across multiple species and tumor histologies is a potential cancer preventative strategy currently being investigated. Companion dogs spontaneously develop cancers at a similar incidence to those in people and are a complementary comparative patient population for the development of novel anti-cancer therapeutics. In addition to an intact immune system with tumors that arise in an autochthonous tumor microenvironment, dogs also have a shorter lifespan and temporally compressed tumor natural history as compared to humans, which allows for more rapid evaluation of safety, immunogenicity, and efficacy of cancer vaccination strategies. Here we describe the study protocol for the Vaccination Against Canine Cancer Study (VACCS), the largest interventional cancer clinical trial conducted in companion dogs to date. In addition to safety and immunogenicity, the primary endpoint of VACCS is the cumulative incidence (CI) of dogs developing malignant neoplasia of any type at the end of the study period. Secondary endpoints include changes in incidence of specific tumor types, survival times following neoplasia diagnosis, and all-cause mortality.


Assuntos
Vacinas Anticâncer , Doenças do Cão , Neoplasias , Animais , Cães , Vacinas Anticâncer/administração & dosagem , Doenças do Cão/prevenção & controle , Neoplasias/prevenção & controle , Neoplasias/veterinária , Microambiente Tumoral , Vacinação/veterinária
3.
Vet Comp Oncol ; 21(4): 717-725, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37705417

RESUMO

Palliative chemotherapy options for dogs with macroscopic non-osseous mesenchymal tumours are limited. The purpose of this study was to assess the response rate of these tumours to carboplatin chemotherapy. Medical records of 28 dogs treated with carboplatin for macroscopic mesenchymal neoplasia between 1990 and 2022 were retrospectively reviewed. Sixteen dogs with soft tissue sarcoma and 12 dogs with haemangiosarcoma were included. Responses observed included one complete response and three partial responses, for an overall response rate of 14.2% (4/28) and median time to progression of 42 days (range 21-259 days). Responses were only seen in patients with haemangiosarcoma, for a response rate of 33.3% (4/12) and median time to progression for responders of 103 days (range 39-252 days). Median time to progression for dogs with metastatic disease was similar to those with only local disease (distant median: 44 days; local median: 23 days, p = 0.56). Dogs with chemotherapy-naïve disease were compared to dogs having received previous chemotherapy treatment and had a median time to progression of 75 days and 40.5 days respectively (p = 0.13). Twenty-two dogs experienced 48 adverse events, with most being grade 1 or 2 (79%). Carboplatin was well tolerated, with variable macroscopic anti-tumour activity and short response duration. Carboplatin may be an acceptable rescue option for dogs with macroscopic haemangiosarcoma, especially those patients that cannot receive doxorubicin.


Assuntos
Antineoplásicos , Doenças do Cão , Hemangiossarcoma , Humanos , Cães , Animais , Carboplatina/efeitos adversos , Antineoplásicos/efeitos adversos , Hemangiossarcoma/veterinária , Estudos Retrospectivos , Doenças do Cão/patologia , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
4.
Parasit Vectors ; 16(1): 288, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587483

RESUMO

BACKGROUND: For decades, zinc sulfate centrifugal fecal flotation microscopy (ZCF) has been the mainstay technique for gastrointestinal (GI) parasite screening at veterinary clinics and laboratories. Elsewhere, PCR has replaced microscopy because of generally increased sensitivity and detection capabilities; however, until recently it has been unavailable commercially. Therefore, the primary aim of this study was to compare the performance of real-time PCR (qPCR) and ZCF for fecal parasite screening. Secondary aims included further characterization of markers for hookworm treatment resistance and Giardia spp. assemblages with zoonotic potential and qPCR optimization. METHODS: A convenience sampling of 931 canine/feline fecal samples submitted to a veterinary reference laboratory for routine ZCF from the Northeast US (11/2022) was subsequently evaluated by a broad qPCR panel following retention release. Detection frequency and agreement (kappa statistics) were evaluated between ZCF and qPCR for seven GI parasites [hookworm/(Ancylostoma spp.), roundworm/(Toxocara spp.), whipworm/(Trichuris spp.), Giardia duodenalis, Cystoisospora spp., Toxoplasma gondii, and Tritrichomonas blagburni] and detections per sample. Total detection frequencies were compared using a paired t-test; positive sample and co-infection frequencies were compared using Pearson's chi-squared test (p ≤ 0.05 significant) and qPCR frequency for hookworm benzimidazole (BZ) resistance (F167Y) and zoonotic Giardia spp. assemblage markers calculated. Confirmatory testing, characterization, and qPCR optimization were carried out with Sanger sequencing. RESULTS: qPCR detected a significantly higher overall parasite frequency (n = 679) compared to ZCF (n = 437) [p = < 0.0001, t = 14.38, degrees-of-freedom (df) = 930] and 2.6 × the co-infections [qPCR (n = 172) vs. ZCF (n = 66)], which was also significant (p = < 0.0001, X2 = 279.49; df = 1). While overall agreement of parasite detection was substantial [kappa = 0.74; (0.69-0.78], ZCF-undetected parasites reduced agreement for individual and co-infected samples. qPCR detected markers for Ancylostoma caninum BZ resistance (n = 5, 16.1%) and Giardia with zoonotic potential (n = 22, 9.1%) as well as two parasites undetected by ZCF (T. gondii/T. blagburni). Sanger sequencing detected novel roundworm species, and qPCR optimization provided detection beyond ZCF. CONCLUSIONS: These results demonstrate the statistically significant detection frequency advantage offered by qPCR compared to routine ZCF for both single and co-infections. While overall agreement was excellent, this rapid, commercially available qPCR panel offers benefits beyond ZCF with detection of markers for Giardia assemblages with zoonotic potential and hookworm (A. caninum) BZ resistance.


Assuntos
Doenças do Gato , Coinfecção , Doenças do Cão , Gastrópodes , Giardíase , Enteropatias Parasitárias , Parasitos , Gatos , Animais , Cães , Estados Unidos , Doenças do Gato/diagnóstico , Doenças do Gato/epidemiologia , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Enteropatias Parasitárias/diagnóstico , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/veterinária , Ancylostoma/genética , Giardia/genética , Reação em Cadeia da Polimerase em Tempo Real
5.
J Am Anim Hosp Assoc ; 59(4): 167-176, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37432790

RESUMO

Canine mast cell tumors (MCTs) have highly variable clinical behavior, and predicting outcomes in individual dogs remains challenging. Many studies combine dogs with varying tumor grades, clinical stage, or treatments, confounding those results. The purpose of this retrospective study was to determine outcome and prognostic factors in a specific subset of dogs with high-grade, stage 2, cutaneous MCTs treated with adequate local control via surgery with or without radiation therapy and adjuvant cytotoxic chemotherapy. Seventeen dogs met the inclusion criteria, and the median survival time was 259 days. Development of local recurrence, tumor location, and presence of ulceration were all associated with shorter survival times. Tumor size, mitotic count, chemotherapy protocol, lymph node classification, and radiation therapy were not significantly associated with outcome. In this study, a specific population of dogs characterized by high-grade MCTs with local lymph node metastasis who received aggressive local and systemic therapy had a median survival of about 8.5 mo. Dogs with ulcerated tumors, recurrent tumors, or tumors located on the head had a worse outcome despite aggressive therapy. These results may serve as a basis of comparison for future research exploring alternative treatment combinations in this specific population of dogs.


Assuntos
Doenças do Cão , Cães , Animais , Doenças do Cão/terapia , Mastócitos , Estudos Retrospectivos , Agressão , Protocolos de Quimioterapia Combinada Antineoplásica
6.
Vet Comp Oncol ; 21(1): 20-27, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36057542

RESUMO

Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days. CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200-250 mg/m2 over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h-1 ; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h × ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200-250 mg/m2 .


Assuntos
Doenças do Cão , Linfoma não Hodgkin , Neoplasias , Humanos , Cães , Animais , Doenças do Cão/tratamento farmacológico , Ciclofosfamida , Neoplasias/veterinária , Linfoma não Hodgkin/veterinária , Área Sob a Curva
7.
J Am Vet Med Assoc ; 260(9): 1-10, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35263294

RESUMO

OBJECTIVE: To determine the clinical and pathological findings of rabbits diagnosed with lymphoma. ANIMALS: 16 rabbits. PROCEDURES: The medical and pathology records database of the Veterinary Medical Teaching Hospital at the University of California, Davis was searched for rabbits diagnosed with lymphoma from 1996 to 2019. RESULTS: Mean age of the 16 rabbits was 8 years (range, 4.5 to 12 years). Immunophenotyping was performed in 14 cases. Diffuse, large, B-cell lymphoma was most common (n = 7) followed by epitheliotropic, T-cell lymphoma (2); type II enteropathy-associated, T-cell lymphoma (2); marginal-zone, B-cell lymphoma (1); peripheral, T-cell lymphoma not otherwise specified (cutaneous nonepitheliotropic lymphoma; 1); primary, mediastinal (thymic) large B-cell lymphoma (1), and unclassified (cytology only with no immunophenotyping; 2). Multiple chemotherapy protocols were used on the basis of each individual animal's disease state. Initial clinical improvement was reported for most rabbits receiving chemotherapy (5/6), with diffuse B-cell lymphoma responding most favorably to treatment. The 11 rabbits included in the survival analysis had a median survival time of 60 days (range, 1 to 480 days), and those diagnosed with B- and T-cell lymphoma had a median survival time of 8 and 36 days (range, 1 to 150 and 1 to 90 days), respectively. CLINICAL RELEVANCE: Rabbits develop a range of lymphoma subtypes and, similar to humans and dogs, diffuse large B-cell lymphoma appears to be the most common. Chemotherapy treatments followed multiple protocols, which were mostly well tolerated and had a highly variable response. Further research into chemotherapy protocols is needed to optimize treatment of lymphoma in rabbits.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Linfoma de Células T , Coelhos , Neoplasias Cutâneas , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/veterinária , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/veterinária , Linfoma de Células T/veterinária , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/veterinária
8.
J Vet Diagn Invest ; 34(3): 465-473, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35291894

RESUMO

Visceral leiomyosarcoma is well described in dogs, but information about non-visceral locations and prevalence is lacking. The diagnosis of leiomyosarcoma is challenging without a gold standard, and often includes the use of immunohistochemical (IHC) stains. We used defined histopathologic patterns, histochemical staining, and IHC staining for smooth muscle actin (SMA), desmin, and laminin to characterize suspected non-visceral leiomyosarcoma in dogs at a single academic institution. In a retrospective search, we identified 24 dogs with a definitive or suspected histologic diagnosis of leiomyosarcoma in a non-visceral location. Histopathology results and clinical details were obtained. Biopsy sections were reviewed by a single pathologist using standardized histologic criteria, including light microscopic appearance, immunohistochemistry (more than two-thirds of neoplastic cells labeled with SMA and desmin or laminin), and histochemical staining (minimal-to-mild matrix deposition by Masson trichrome). Of the 24 cases of possible non-visceral leiomyosarcomas, 4 were consistent with a definitive diagnosis of non-visceral leiomyosarcoma (3) or leiomyoma (1) based on the established criteria. Only the leiomyoma had more than two-thirds of neoplastic cells label with all 3 markers; all 3 leiomyosarcomas had more than two-thirds of neoplastic cells label with SMA and laminin. Our data highlight the uncommon nature of non-visceral leiomyosarcoma and the importance of IHC for their diagnosis. A definitive diagnosis could not be made based on SMA alone, and desmin was not useful in this cohort. Further studies are needed to clarify the histopathologic, IHC, and clinical features of canine non-visceral SMA-positive mesenchymal tumors.


Assuntos
Doenças do Cão , Leiomioma , Leiomiossarcoma , Animais , Desmina , Doenças do Cão/diagnóstico , Cães , Humanos , Laminina , Leiomioma/diagnóstico , Leiomioma/patologia , Leiomioma/ultraestrutura , Leiomioma/veterinária , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/veterinária , Estudos Retrospectivos
9.
Vet Comp Oncol ; 20(2): 458-464, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34878710

RESUMO

Primary pulmonary histiocytic sarcoma (PHS) is a rare form of dendritic cell or macrophage neoplasia originating within the pulmonary parenchyma. There is limited literature describing prognosis in dogs with PHS receiving curative-intent treatment consisting of surgical excision and adjuvant chemotherapy. The primary objective of this study was to report outcomes in dogs with localized PHS treated with standardized local and systemic therapy. A secondary objective was to identify prognostic factors in this population. A multi-institutional retrospective study was performed and medical records including all surgical and histopathologic reports were retrospectively reviewed. For inclusion, dogs were required to have confirmed localized PHS and they must have undergone curative-intent surgery with resection of all gross primary tumour and enlarged tracheobronchial lymph nodes; additionally, they must have received curative-intent treatment with adjuvant single-agent CCNU chemotherapy. Twenty-seven dogs from six veterinary teaching hospitals and five private practices treated from 2008-2019 were included. The overall median survival time was 432 days. Higher CCNU dose was demonstrated to have a negative impact on survival on univariate, but not multivariable, analysis. Factors that were not found to be associated with survival on univariate analysis included body weight, breed, clinical signs at the time of diagnosis, hypoalbuminaemia, tumour size, lung lobe affected, lymph node metastasis, surgical margins and CCNU dose reductions. This study supports a favourable prognosis for dogs diagnosed with localized PHS treated with curative-intent surgery in addition to adjuvant CCNU chemotherapy and suggests that multimodal treatment may be advisable to attempt to prolong survival.


Assuntos
Doenças do Cão , Sarcoma Histiocítico , Neoplasias Pulmonares , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia , Cães , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/veterinária , Lomustina/uso terapêutico , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/veterinária , Estudos Retrospectivos , Resultado do Tratamento
10.
J Am Vet Med Assoc ; 259(10): 1154-1162, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34727073

RESUMO

OBJECTIVE: To describe the procedure of prostatic artery embolization (PAE) in dogs with prostatic carcinoma and to evaluate the short-term outcome for treated dogs. ANIMALS: 20 client-owned dogs with prostatic carcinomas between May 2014 and July 2017. PROCEDURES: In this prospective cohort study, dogs with carcinoma of the prostate underwent PAE with fluoroscopic guidance. Before and after PAE, dogs underwent CT and ultrasonographic examinations of the prostate, and each owner completed a questionnaire about the dog's clinical signs. Results for before versus after PAE were compared. RESULTS: Prostatic artery embolization was successfully performed in all 20 dogs. Tenesmus, stranguria, and lethargy were significantly less common 30 days after PAE (n = 2, 1, and 0 dogs, respectively), compared with before PAE (9, 10, and 6 dogs, respectively). Median prostatic volume was significantly less 30 days after PAE (14.8 cm3; range, 0.4 to 48.1 cm3; interquartile [25th to 75th percentile] range, 6.7 to 19.5 cm3), compared with before PAE (21.7 cm3; range, 2.9 to 77.7 cm3; interquartile range, 11.0 to 35.1 cm3). All dogs had a reduction in prostatic volume after PAE, with a median prostatic volume loss of 39.4% (95% CI, 20.3% to 59.3%). CONCLUSIONS AND CLINICAL RELEVANCE: Prostatic artery embolization was associated with decreased prostate volume and improved clinical signs in this cohort. The short-term response to PAE appears promising, and evaluation of the long-term impact on survival time is needed.


Assuntos
Carcinoma , Doenças do Cão , Embolização Terapêutica , Hiperplasia Prostática , Animais , Artérias , Carcinoma/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/terapia , Cães , Embolização Terapêutica/veterinária , Masculino , Estudos Prospectivos , Hiperplasia Prostática/terapia , Hiperplasia Prostática/veterinária , Resultado do Tratamento
11.
Front Vet Sci ; 8: 647846, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277751

RESUMO

Zoledronic acid (ZOL) is an intravenous bisphosphonate indicated for the use of hypercalcemia of malignancy and management of bony metastases. Its therapeutic effect lies in the targeting of malignant osteoclasts; however, administration can be associated with renal toxicity. The objective of this retrospective study was to evaluate the frequency and severity of acute kidney injury (AKI) following ZOL administration in a cohort of cancer-bearing dogs. A pharmacy search was conducted to identify dogs that received a dose of ZOL between June 2016 and July 2019. Inclusion criteria included baseline and post-treatment chemistry panels. Medical records were reviewed to obtain clinical data including signalment, dose, dosage, number of treatments administered, and changes in renal function. Forty-four dogs met the inclusion criteria. Median number of doses administered was three [interquartile range (IQR), 2-5]. The median highest creatinine value occurred after a median of one dose (IQR, 1-2 doses) compared with the median highest value of blood urea nitrogen, phosphorus, and potassium, which occurred after a median of two doses (IQR, 1-3). Six (13.6%) dogs developed an AKI, and one dog (2.3%) had progression of an existing azotemia after treatment with ZOL was initiated. Two dogs (4.5%) had ZOL treatment discontinued secondary to development of azotemia. Use of concurrent administration of non-steroidal anti-inflammatory drugs or anesthesia did not significantly increase the risk of AKI in this cohort of dogs. Acute kidney injury is observed infrequently in cancer-bearing dogs treated with ZOL and is generally mild to moderate in severity; discontinuation of ZOL due to AKI is uncommon.

12.
Vet Clin Pathol ; 50(1): 71-75, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33745143

RESUMO

A 3-year-old dog was referred to the Veterinary Medical Teaching Hospital of the University of California-Davis for further evaluation of episodes of epistaxis of 1-year duration and peripheral lymphadenopathy. The patient had a history of atopic dermatitis with no travel history outside of California. Hyperglobulinemia with a polyclonal gammopathy was noted on serum protein electrophoresis. Microscopic evaluation of a bone marrow aspirate sample revealed many free and intra-cellular amastigotes of Leishmania sp. that was further confirmed by qPCR as L infantum. This is, to the best of our knowledge, the first reported case of canine leishmaniasis in the state of California. The patient is believed to have been vertically infected from the dam who is from Serbia and remained subclinical until presentation. Because the clinical progression of leishmaniasis is variable, it is important that precautions be discussed with owners acquiring puppies with dams from endemic regions of leishmaniasis to prevent zoonotic exposure in states where competent vectors are present.


Assuntos
Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Leishmaniose , Animais , Doenças do Cão/diagnóstico , Cães , Leishmaniose/diagnóstico , Leishmaniose/veterinária , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/veterinária , Reação em Cadeia da Polimerase em Tempo Real/veterinária
13.
Clin Cancer Res ; 27(11): 3005-3016, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33753454

RESUMO

PURPOSE: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. PATIENTS AND METHODS: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. RESULTS: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144-237] and 282 days (95% CI, 224-383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157-217) and 280 days (95% CI, 252-332), respectively. CONCLUSIONS: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.


Assuntos
Neoplasias Ósseas/terapia , Neoplasias Ósseas/veterinária , Doenças do Cão/terapia , Osteossarcoma/terapia , Osteossarcoma/veterinária , Animais de Estimação , Sirolimo/administração & dosagem , Amputação Cirúrgica , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Carboplatina/administração & dosagem , Quimioterapia Adjuvante , Terapia Combinada/veterinária , Doenças do Cão/mortalidade , Cães , Osteossarcoma/genética , Osteossarcoma/mortalidade , Estudos Prospectivos , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Taxa de Sobrevida , Serina-Treonina Quinases TOR/metabolismo , Resultado do Tratamento
14.
Vet Ophthalmol ; 24(3): 301-307, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33616294

RESUMO

OBJECTIVE: To report onset and progression of clinical signs of a neuroendocrine neoplasm (NEN) presumed metastatic to the choroid in a dog. ANIMALS STUDIED: A 7.5-year-old female spayed German shepherd dog mix referred for advanced imaging and evaluation of a subretinal mass in the right eye. PROCEDURES: Procedures performed included general physical and ophthalmic examinations; ocular, orbital, and abdominal ultrasonography; thoracic radiographs; cranial magnetic resonance imaging; serologic testing for infectious agents; analysis of hematologic as well as serum and urine biochemical parameters; echocardiography; electrocardiography; cytologic assessment of lymph nodes; and histopathology and immunohistochemistry of the enucleated globe. RESULTS: Examination and imaging identified a pigmented mass within and expanding the superior choroid. Following enucleation, a choroidal NEN with tumor emboli in scleral blood vessels was diagnosed by histopathologic assessment and confirmed by immunohistochemical labelling. Despite extensive and repeated diagnostic testing over many months, a putative primary site was not identified until 19 months after the initial ocular signs were noted. At that time, a heart-base mass and congestive heart failure were highly suggestive of a chemodectoma. CONCLUSION: This comprehensive report of a NEN presumed metastatic to the choroid in a dog suggests that ocular disease can be a very early and solitary sign of NEN in the dog.


Assuntos
Neoplasias da Coroide/veterinária , Doenças do Cão/diagnóstico , Neoplasias Cardíacas/veterinária , Paraganglioma Extrassuprarrenal/veterinária , Animais , Neoplasias da Coroide/diagnóstico , Neoplasias da Coroide/secundário , Diagnóstico Diferencial , Cães , Enucleação Ocular , Feminino , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/patologia , Paraganglioma Extrassuprarrenal/diagnóstico , Paraganglioma Extrassuprarrenal/secundário , Linhagem
15.
Vet Comp Oncol ; 19(3): 463-472, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32892513

RESUMO

Tumour stage has been demonstrated to have prognostic significance in canine oral malignant melanoma (OMM). Various evaluation techniques of positron emission tomography/computed tomography (PET/CT) have been reported for staging of head-and-neck tumours in people, but canine-specific data are limited, and reports for CT accuracy have been variable. In this prospective study, the head/neck of client-owned dogs with cytologically or histologically diagnosed OMM were imaged with 18 Fluorine-fluorodeoxyglucose (18 F-FDG) PET/ CT. Bilateral mandibular lymphadenectomy was performed for histopathologic assessment. Two evaluation techniques for CT and PET were applied by four independent observers. CT evaluation utilized both a standardized grading scheme and a subjective clinical interpretation. PET evaluation was first performed solely on 18 F-FDG-uptake in lymph nodes compared to background on a truncated scan excluding the oral cavity. Subsequently, the entire head/neck scan and standardized uptake value (SUV) measurements were available. Receiver operating characteristic analysis was performed with histopathology as gold standard. Twelve dogs completed the study and metastatic OMM was identified in six mandibular lymph nodes from five dogs. Of the CT-interpretation techniques, use of clinical grading performed best (sensitivity = 83% and specificity = 94%). Both PET techniques resulted in 100% sensitivity, but primary tumour site evaluation and use of SUV increased specificity from 78% to 94%. The SUVmax cut-point, 3.3, led to 100% sensitivity and 83% specificity. In this population of dogs, PET appeared to be highly sensitive but at risk of being less specific without use of appropriate parameters and thresholds.


Assuntos
Doenças do Cão , Melanoma , Neoplasias Bucais/veterinária , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Animais , Doenças do Cão/diagnóstico por imagem , Cães , Fluordesoxiglucose F18 , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Melanoma/diagnóstico por imagem , Melanoma/veterinária , Neoplasias Bucais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/veterinária , Estudos Prospectivos , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Neoplasias Cutâneas , Melanoma Maligno Cutâneo
16.
Vet Comp Oncol ; 19(1): 191-200, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33135852

RESUMO

Published radiotherapy results for suspected heart-based tumours in dogs are limited. In this retrospective longitudinal study (3/2014-2019), eight dogs with either clinical signs attributable to a heart-base mass (6), or asymptomatic with a progressively larger mass on echocardiogram (2), received conventional fractionated radiotherapy (CFRT) or stereotactic body radiotherapy (SBRT). Clinical findings in symptomatic cases included one or more of the following: retching/coughing (4), exercise intolerance (2), collapse (1), pericardial effusion (2), rare ventricular premature contractions (2), abdominal effusion (1), or respiratory distress due to chylothorax (1). CFRT cases received 50 Gray (Gy) in 20 fractions and SBRT cases received 30 Gy in 5 or 24 Gy in three fractions. Two dogs received chemotherapy post-radiation. At analysis, 7/8 dogs were deceased and one was alive 684 days post-treatment. The estimated median overall survival (MOS) from first treatment was 785 days (95% CI 114-868 days, [range 114-1492 days]). Five dogs received CFRT (MOS 817 days; (95% CI 155 days-not reached [range 155-1492 days])). Three dogs received SBRT with one alive at analysis (MOS 414 days, (95% CI, 114 days-not reached [range 114-414 days])). No statistically significant difference was found between survival for CFRT and SBRT. Of the symptomatic patients, 5/6 showed improvement. Mass size reduced in 4/5 cases receiving follow-up ultrasounds. Possible complications included asymptomatic radiation pneumonitis (4), atrial tachycardia/premature beats (4) and pericardial effusion with heart failure coincident with tumour progression (1). This study provides preliminary evidence that radiotherapy may impact clinically relevant or progressively enlarging heart-base masses.


Assuntos
Doenças do Cão/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Cardíacas/veterinária , Radiocirurgia/veterinária , Animais , Cães , Feminino , Masculino
17.
Vet Radiol Ultrasound ; 60(5): 560-566, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31313406

RESUMO

Ultrasonography provides a minimally invasive method to evaluate the cervical lymph nodes in dogs as part of staging head and neck cancer; however, standardized cohesive reports of the normal lymph node size and appearance are lacking. The purpose of this prospective, descriptive, reference interval study was to characterize the ultrasonographic appearance of cervical lymph nodes in 27 clinically healthy dogs. The size, shape, echogenicity, and margination of the mandibular, medial retropharyngeal, and superficial cervical lymph nodes were evaluated and correlated with age, breed, sex, body weight, and stage of dental disease. The appearance of the lymph nodes was variable among the population. The majority were cigar or ovoid in shape with smooth margins. The echogenicity of the mandibular lymph nodes was predominantly hypoechoic whereas the medial retropharyngeal lymph nodes were predominantly isoechoic compared to the salivary glands. The superficial cervical lymph nodes were predominantly hyperechoic to the surrounding muscle bellies. Higher body weight and younger age were associated with increased size in the medial retropharyngeal and superficial cervical lymph nodes (P-values < .05). Sex and breed were not found to correlate with lymph node characteristics, and there was no trend noted in lymph node appearance associated with dental disease. These data establish normal parameters for the ultrasonographic size and appearance of cervical lymph nodes in dogs and can provide a reference of comparison for future canine cervical ultrasounds, which can be considered for routine staging procedures for head and neck cancer.


Assuntos
Cães/anatomia & histologia , Linfonodos/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Ultrassonografia/veterinária , Fatores Etários , Animais , Peso Corporal , Feminino , Masculino , Estudos Prospectivos , Valores de Referência , Fatores Sexuais , Especificidade da Espécie
18.
Front Vet Sci ; 6: 180, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31245395

RESUMO

Positron Emission Tomography (PET) is an imaging technique that provides functional information, in addition to structural information obtained with computed tomography (CT). The most common application is cancer staging, using 18F-Fluorodeoxyglucose (18F-FDG), a radioactive analog of glucose. Although limited data are available in the veterinary literature, human studies have demonstrated benefit with the addition of PET both for assessment of the primary tumor and for detection of metastatic disease. 18F-FDG PET appears to be more accurate at detecting the margin of oral neoplasia, in particular for tumors arising from highly vascularized tissue, such as the lingual and laryngeal areas. 18F-FDG PET has a high sensitivity for the detection of lymph node metastasis, however the specificity is variable between studies. Tracers beyond 18F-FDG can also be used for oncology imaging. 18F-Fluoride (18F-NaF) is an excellent osseous tracer, useful in assessing bone involvement of primary tumors or osseous metastasis. Other specific tracers can be used to assess cell proliferation or hypoxia for tumor characterization. 18F-FDG is also an excellent tracer for detection of inflammation. Human studies have demonstrated its value for the assessment of periodontitis and dental implant infection. 18F-NaF has been used to assess disorders of the temporomandibular joint in the human literature, demonstrating good correlation with arthralgia and therapeutic outcome. Both 18F-NaF and 18F-FDG had good concordance with localization of cervical pain in people. PET will likely have a growing role in veterinary medicine not only for oncologic imaging but also for assessment of inflammation and pain.

19.
J Am Anim Hosp Assoc ; 55(4): e55402, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31099610

RESUMO

An 8 yr old female spayed poodle/terrier mixed-breed dog was referred for evaluation of a recurrent and metastatic ovarian dysgerminoma. A total dose of 20Gy was administered to both the mediastinal metastatic lesion and retroperitoneal recurrent dysgerminoma in five daily fractions of 4Gy. Acute side effects were mild and self-limiting. This was followed by several courses of chemotherapy using a variety of agents. Despite extensive disease, this patient was still alive at the time of publication, 524 days after presentation and 501 days following completion of radiation. This case report demonstrates tolerability and efficacy of palliative radiation and chemotherapy for this rare tumor type.


Assuntos
Antineoplásicos/uso terapêutico , Doenças do Cão/terapia , Disgerminoma/veterinária , Doenças Ovarianas/veterinária , Radioterapia/veterinária , Animais , Cães , Disgerminoma/patologia , Disgerminoma/terapia , Feminino , Doenças Ovarianas/patologia , Doenças Ovarianas/terapia
20.
Vet Comp Oncol ; 17(2): 130-138, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30684311

RESUMO

Squamous cell carcinoma (SCC) is a frequently recognized dermal tumour in dogs and has been described as a common pathology induced by solar ultraviolet radiation exposure. Little has been published about this neoplasm with regard to clinical features and outcome in dogs. This retrospective study included 193 dogs from a single institution histopathologically diagnosed with SCC of the dermis. Thirty-eight percent of all dogs had documented histopathologic actinic change. The overall median survival time was 1004 days, with the population demonstrating actinic change associated with a significantly longer survival time (median 1359 days, range 16-3530 days) compared to dogs without actinic change (median 680 days, range 16-3066 days) and this achieved significance on multivariate analysis (hazard ratio 0.42, 95% confidence interval 0.193-0.930, P = 0.032). These data demonstrate increased survival of dogs with SCC demonstrating actinic change over those with non-actinic SCCs, and purports long-term survival for these animals. Dogs received a variety of treatment approaches as a retrospective study, and future prospective studies will be necessary to investigate whether adjunct therapies such as radiation or chemotherapy offer improvement in survival for dermal SCC in the dog.


Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças do Cão/patologia , Ceratose Actínica/veterinária , Neoplasias Cutâneas/veterinária , Animais , California , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Comorbidade , Doenças do Cão/etiologia , Doenças do Cão/terapia , Cães , Feminino , Ceratose Actínica/etiologia , Ceratose Actínica/patologia , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Faculdades de Medicina Veterinária , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Sobrevida , Resultado do Tratamento , Raios Ultravioleta/efeitos adversos
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