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Small cell intestinal lymphoma has not been well characterized in dogs. The objective of this study was to describe clinical characteristics and outcome in dogs with small cell intestinal lymphoma. We hypothesized that affected dogs would have prolonged survival compared with high-grade gastrointestinal (GI) lymphoma. Pathology records were searched for dogs with histologically confirmed small cell GI lymphoma. Seventeen dogs with confirmed small cell intestinal lymphoma were identified, and clinical and outcome data were retrospectively collected. Histopathology was reviewed by a board-certified pathologist, and tissue sections were subjected to immunophenotyping and molecular clonality assessment. All dogs had small cell, T-cell, lymphoma confirmed within various regions of small intestine, with 1 dog also having disease in abdominal lymph nodes. All dogs had clinical signs attributable to GI disease; diarrhoea (n = 13) was most common. Ultrasonographic abnormalities were present in 8 of 13 dogs with abnormal wall layering (n = 7) and hyperechoic mucosal striations (n = 7) representing the most common findings. In total, 14 dogs received some form of treatment. The median survival time (MST) for all dogs was 279 days and the MST for the 14 dogs that received any treatment was 628 days. Dogs with anaemia and weight loss at presentation had significantly shorter survival times and dogs that received a combination of steroids and an alkylating agent had significantly longer survival times. Small cell, T-cell, intestinal lymphoma is a distinct disease process in dogs, and those undergoing treatment may experience prolonged survival.

BackgroundPeripheral blood hematopoietic cell transplantation (PBHCT) is a feasible treatment option for dogs with B-cell lymphoma.ObjectiveTo examine apheresis and PBHCT outcomes in dogs diagnosed with T-cell lymphoma (TCL).AnimalsFifteen client-owned dogs diagnosed with high-grade TCL.MethodsAfter high-dose cyclophosphamide and rhG-colony-stimulating (rhG-CSF) factor treatment, peripheral blood mononuclear cells were collected using cell separators. The harvested cells then were infused after varying doses of total body irradiation (TBI). Postirradiation adverse effects were managed symptomatically and dogs were discharged upon evidence of hematopoietic engraftment.ResultsMore than 2 × 10(6) CD34+ cells/kg were harvested from 15/15 dogs. Thirteen of 15 (87%) dogs engrafted appropriately, whereas 2 (13%) of the dogs died in the hospital. One dog developed cutaneous B-cell lymphoma 120 days post-PBHCT. The median disease-free interval and overall survival (OS) of the 13 dogs transplanted in first remission from the time of PBHCT were 184 and 240 days, respectively. Stage and substage of disease at diagnosis had no effect on OS. Two of 13 (15%) dogs were alive 741 and 772 days post-PBHCT.Conclusions and clinical importancePBHCT may be considered as a treatment option for dogs with TCL.

Objective: To determine the prevalence of undiagnosed malignant neoplasms in a cohort of healthy middle-aged to older dogs., Methods: Healthy, client-owned dogs between the ages of 5.5 and 11.5 years and of mixed breed or breeds overrepresented for death due to cancer were screened for eligibility to participate in the Vaccination Against Canine Cancer Study at 3 study sites from May 6, 2019, to June 21, 2022. Physical examination with rectal evaluation and aspiration cytology of dermal and subcutaneous masses, CBC, biochemical profile, urinalysis, 3-view thoracic radiographs, and abdominal ultrasound were performed to identify occult cancer or other serious disease in all patients prior to study enrollment., Results: 902 dogs were screened for participation in the Vaccination Against Canine Cancer Study. At the time of screening, 24 dogs (2.7%) were diagnosed with cancer, while another 30 dogs (3.3%) had abnormalities identified for which malignant neoplasia could not be ruled out but was not definitively confirmed. The prevalence of confirmed cancer in this population was 2.7% and 6.0% when cases in which malignant neoplasia was suspected were included. For the 24 dogs definitively diagnosed with cancer, the diagnosis was made on the basis of physical examination with aspiration cytology of a dermal or subcutaneous mass for 20 dogs (83%)., Conclusions: Routine physical examination was able to detect the majority of the malignant tumors in this population of dogs., Clinical Relevance: A thorough physical examination, including rectal examination, with aspiration cytology of dermal or subcutaneous lesions is a critical component of cancer screening for middle-aged and older dogs.

Data regarding the outcome of canine rib chondrosarcoma is sparse and varied. While grade of tumour is associated with outcome for canine appendicular chondrosarcoma, the association of grade with outcome for canine rib chondrosarcoma is unclear. This study aimed to correlate the grade of canine rib chondrosarcoma with median survival time. Retrospectively, cases of primary rib chondrosarcoma were identified, and tumours were graded based on a 3-tier adapted human grading scheme. Twenty-two patients were included in the survival analysis. The median survival time was 1427 days (range: 27-3354 days). This was not significantly different for patients with grade I versus II versus III (p = 0.82), grade I-II versus III (p = 0.34), or grade I versus II-III (p = 0.49). No variables assessed including age, weight, tumour location (cranial vs. caudal thorax; left vs. right hemithorax), tumour location on rib (proximal, middle, and distal), radiographic appearance (lytic, proliferative, or mixed), elevated serum alkaline phosphatase activity, grade, grade specific histologic features (matrix production, architecture, pleomorphism, cellularity, necrosis, and total score), adjunct therapy post-surgical excision, development of metastatic disease post-surgery, or local recurrence post-surgery were found to impact the risk of death due to chondrosarcoma. In this limited group of patients, the grading scheme reported here, and the other variables assessed did not appear to offer additional prognostic information. However, this data must be interpreted considering the small sample size and thus low statistical power. Additional studies are needed to determine the true impact of grade on outcome for canine rib chondrosarcomas., (© 2024 The Author(s). Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

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., Competing Interests: Declaration of competing interest All authors are employees (CML, MDE, JLW, CM, CEL, JT, SL, KM, JA, CS) or consultants (HR, HLR) for Antech Diagnostics, Inc., Mars Petcare Science & Diagnostics., (Copyright © 2024. Published by Elsevier Ltd.)

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., Competing Interests: Declaration of Competing Interest SAJ, KFS and DHT are shareholders in Calviri Inc., which is commercializing the described frameshift vaccination technology. JLW is currently an employee of Antech Diagnostics, however this organization did not participate in funding this work. JHB, DMV, JE, JRB, LS, RLP, SA, AJ, DB, JR, IM, IDK, MKH, RH, and BMS declare they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

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., (© 2023 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

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, X 2  = 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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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., (© 2023 by American Animal Hospital Association.)

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/m 2 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/m 2 ., (© 2022 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

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., (© 2021 John Wiley & Sons Ltd.)

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.

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.

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.

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., (© 2020 John Wiley & Sons Ltd.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vidal, Skorupski, Willcox, Palm and Burton.)

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., (©2021 American Association for Cancer Research.)

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., (© 2020 John Wiley & Sons Ltd.)

Background: Doxorubicin (DOX) is one of the most effective chemotherapeutics for canine high-grade lymphoma. In addition to dose-dependent chronic cardiotoxicity, DOX can trigger acute cardiac arrhythmias during drug infusion. Diphenhydramine premedication is commonly used, as histamine release is a proposed mechanism for DOX-associated arrhythmogenesis. Hypothesis/Objectives: The study objectives were to evaluate the incidence and severity of DOX infusion-related cardiac arrhythmias in dogs with high-grade lymphoma and evaluate the effect of diphenhydramine premedication on arrhythmia frequency and severity during and after DOX infusion. Animals: Twenty-two client-owned dogs with cytologically/histopathologically confirmed high-grade lymphoma were recruited, of which 19 were enrolled and 9 completed the study. Methods: Dogs were screened by echocardiogram and concurrent electrocardiogram for this randomized prospective crossover study. Group A received no premedication for DOX #1 and was premedicated with diphenhydramine for DOX #2; Group B received diphenhydramine with DOX #1 and no premedication for DOX #2. For both visits, Holter monitor data were collected for 1 h pre-DOX and 3 h post-DOX administration. Results: Nineteen dogs were enrolled and 9 dogs [Group A (5), Group B (4)] completed the protocol. There was no statistical difference between the DOX alone and DOX + diphenhydramine when evaluating the total number of ventricular premature complexes (VPCs, P = 0.34), change in VPCs/hour ( P = 0.25), total number of atrial premature complexes (APCs, P = 0.5), change in APCs/hour ( P = 0.06), or ventricular arrhythmia severity score ( P > 0.99). Conclusions and clinical importance: This study demonstrates that in these dogs with rigorous pretreatment cardiovascular screening, DOX infusion did not induce significant arrhythmias. Furthermore, these data suggest that, with this screening approach, diphenhydramine may not alter the arrhythmia number or severity in canine DOX recipients., (Copyright © 2020 Willcox, Belanger, Burton, Yu, Ueda, Visser, Skorupski and Stern.)

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., (© 2019 American College of Veterinary Radiology.)

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.

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 18 F-Fluorodeoxyglucose ( 18 F-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. 18 F-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. 18 F-FDG PET has a high sensitivity for the detection of lymph node metastasis, however the specificity is variable between studies. Tracers beyond 18 F-FDG can also be used for oncology imaging. 18 F-Fluoride ( 18 F-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. 18 F-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. 18 F-NaF has been used to assess disorders of the temporomandibular joint in the human literature, demonstrating good correlation with arthralgia and therapeutic outcome. Both 18 F-NaF and 18 F-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.

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., (© 2019 John Wiley & Sons Ltd.)

Background: A doxorubicin (DOX)-based chemotherapy protocol, CHOP, is the most effective treatment for canine high-grade B-cell lymphoma; however, the cost and time requirements associated with this protocol are not feasible for many pet owners. An alternative treatment option is the use of DOX, the most effective drug, in combination with prednisone. Prior studies with single-agent DOX included dogs with T-cell lymphoma, a known negative prognostic factor, which may have resulted in shorter reported survival times than if dogs with B-cell lymphoma were analyzed separately. The purpose of this study was to evaluate the outcome of dogs with high-grade B-cell lymphoma when treated with DOX and prednisone with or without L-asparaginase (L-ASP). Identification of prognostic factors was of secondary interest., Results: Thirty-three dogs were included in the study; 31 dogs were evaluable for response with an overall response rate of 84%. The median progression free survival (PFS) and overall survival (OS) were 147 days and 182 days, respectively. The one-year survival fraction was 23%. No variable other than protocol completion was found to be significant for either PFS or OS including historical prognostic factors such as substage, thrombocytopenia, and body weight., Conclusions: Dogs with high-grade B-cell lymphoma treated with DOX and prednisone with or without L-ASP have similar response rates, PFS, and OS to prior studies that did not differentiate between lymphoma immunophenotype. This protocol is not a replacement for CHOP; however, it is an alternative if time and cost are factors, while providing therapeutic benefit greater than prednisone alone.

Vitamin D concentrations show an inverse correlation with incidence of certain tumors in people and dogs. Additionally, human osteosarcoma has been associated with dysregulation of vitamin D-dependent pathways. The study objective was to compare serum 25-hydroxyvitamin D 2 and 25-hydroxyvitamin D 3 in 20 dogs with osteosarcoma to age- and weight-matched control dogs. We hypothesized that dogs with osteosarcoma would have lower serum 25-hydroxyvitamin D than control dogs. The mean 25-hydroxyvitamin D 3 concentrations for dogs with osteosarcoma and matched-controls were 34.95 ng/mL and 33.85 ng/mL, respectively (P = 0.784). Based on these data, 25-hydroxyvitamin D insufficiency might not be important in the pathogenesis of canine osteosarcoma., (Published by Elsevier Ltd.)

History: CaridianBCT apheresis machines require a ~285 mL priming volume (extracorporeal blood) that is withdrawn from the patient in ~10 minutes. Therefore, apheresis in dogs has generally been limited to dogs > ~20 kg to assure <20% of the blood volume is removed in the priming phase. ANIMALS/PHYSICAL EXAMINATION: Three dogs weighing <14 kg (13.6, 10.5, and 9.9 kg) with lymphoma that underwent apheresis., Management: The dogs were premedicated for placement of apheresis catheters with hydromorphone (0.1 mg kg(-1) ) IM. Anesthesia was induced with propofol, to effect, intravenously and general anesthesia was maintained with isoflurane in oxygen. Following catheter placement, dogs were allowed to recover from isoflurane but were kept sedated with either a dexmedetomidine constant rate infusion (CRI) or a propofol CRI. Real time autologous blood priming was not performed in any of the dogs. Instead, priming solutions were composed of a combination of hetastarch, lactated Ringer's solution, and/or autologous blood that was harvested 4 days before the procedure. During apheresis, dogs received anticoagulant citrate-dextrose, solution-A (ACD-A) to prevent clotting and 10% calcium gluconate as needed to maintain normal ionized calcium concentrations. Dogs were monitored for cardiovascular and cardiopulmonary stability, anemia and lactic acidosis., Follow-Up: All of the dogs had cardiovascular and cardiopulmonary values within clinically acceptable ranges. Immediately following apheresis all of the dogs were mildly to moderately anemic (PCV; 17-35%) although none of the dogs required a transfusion or had an increased lactate concentration., Conclusions: Dogs as small as 9.9 kg can successfully undergo apheresis with a variety of priming solutions. Dexmedetomidine or propofol given as a CRI provides sufficient sedation for this procedure., (© 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Background: Peripheral blood CD34+ hematopoietic cell transplantation (PBHCT) is commonly used to treat human patients with relapsed non-Hodgkin diffuse, large B-cell lymphoma with cure rates approaching 50%., Objective: To determine the safety and feasibility of performing PBHCT to treat canine B-cell lymphoma (LSA) patients in a clinical academic setting., Animals: Twenty-four client-owned dogs diagnosed with B-cell LSA., Methods: After high-dose cyclophosphamide and rhG-colony-stimulating factor treatment, peripheral blood mononuclear cells were collected using cell separator machines. The harvested cells then were infused after a 10 Gy dose of total body irradiation (TBI). Post-irradiation adverse effects were managed symptomatically and dogs were discharged upon evidence of engraftment., Results: More than 2 × 10(6) CD34+ cells/kg were harvested in 23/24 dogs. Preapheresis peripheral blood monocyte count was correlated with the number of CD34+ cells/kg harvested. Twenty-one of 24 (87.5%) dogs engrafted appropriately, whereas 2 dogs (8.3%) died in the hospital. One (5%) dog exhibited delayed engraftment and died 45 days after PBHCT. One dog developed presumed TBI-induced pulmonary fibrosis approximately 8 months after PBHCT. The median disease-free interval and overall survival (OS) of all dogs from the time of PBHCT was 271 and 463 days, respectively. Five of 15 (33%) dogs transplanted before they relapsed remain in clinical remission for their disease at a median OS of 524 days (range, 361-665 days)., Conclusions and Clinical Importance: In most cases, PBHCT led to complete hematologic reconstitution. Therefore, PBHCT may be considered as a treatment option for dogs with B-cell lymphoma., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)