The incidence and trends of proteinuria, azotemia and hypertension in cats receiving toceranib phosphate.

OBJECTIVES: This retrospective study aimed to determine the incidence and trends of proteinuria, elevations in serum creatinine and urea, and systolic blood pressure in cats undergoing treatment with toceranib. METHODS: In total, 32 cats treated with toceranib for malignancies were analyzed. Cats were included if urinalysis and urine protein:creatinine ratio (UPC) measurements were available at 28 days (T1) and 56 days (T2) after starting the treatment. Cats with concurrent lower urinary tract disease, including urinary tract malignancy, were excluded. Friedman's ANOVA compared variables between time points, and the Spearman test assessed the correlation between treatment duration and UPC. RESULTS: The median starting dose of toceranib was 2.68 mg/kg (range 1.7-3.9). In total, 15 (46.9%) cats received concurrent non-steroidal anti-inflammatory drugs. The most commonly treated tumors were oral squamous cell carcinoma (n = 10) and mast cell tumor (n = 5). None of the 32 cats developed progressive proteinuria or azotemia during the follow-up period (median 56 days; range 56-336). Notably, UPC and serum creatinine were significantly lower at T2 compared with baseline (P = 0.012 and 0.001, respectively). Among the four cats with baseline proteinuria, UPC decreased over time with or without concurrent telmisartan treatment (n = 2). All four of these cats experienced a reduction in tumor size with toceranib concurrently with their decreased UPC. There was no significant correlation between UPC and the duration of toceranib treatment (P = 0.089). Blood pressure was not significantly different over the assessed time points. CONCLUSIONS AND RELEVANCE: The incidence of proteinuria, renal azotemia and hypertension in cats treated with toceranib for neoplasia appears to be low. Toceranib may be a viable treatment option even in cats with pre-existing proteinuria or renal disease, with careful monitoring of trends recommended.

Evaluation serum soluble interleukin 2 receptor with diagnosis and prognosis in canine solid tumour: 34 cases.

BACKGROUND/AIM: The soluble interleukin-2 receptor (sIL-2R) serve as a valuable biomarker for tumors in human patients, as its levels increase during the activation of T lymphocytes in clinical states such as inflammation, infection, and tumor. This study aimed to demonstrate that sIL-2R levels can be also elevated in dogs with tumors and evaluate its applicability as a diagnostic and prognostic factor in canine cancer patients. PATIENTS AND METHODS: Serum was collected from 6 healthy dogs and 34 dogs with solid tumors. The concentration of sIL-2R was measured using a commercial enzyme-linked immunosorbent assay kit. RESULTS: The median sIL-2R concentration was significantly higher in dogs with solid masses than in healthy dogs (117.3 vs 68.33 pg/ml, p = 0.016). The highest median sIL-2R concentration was found in dogs with malignant tumors, followed by those with benign tumors, and healthy dogs (119.6 vs 93.74 vs 68.33 pg/ml, respectively). In dogs with malignant tumors, the mortality rate was significantly higher in the group with high sIL-2R levels than in the group with low sIL-2R levels. Dogs with solid tumors, particularly those with malignant tumors, had higher concentrations of sIL-2R than healthy dogs. Among dogs with malignant tumors, a correlation between sIL-2R concentration and mortality rate was confirmed. CONCLUSION: Serum sIL-2R levels may be used to detect malignant tumors and serve as a prognostic factor in dogs with malignant tumors.

Genomic profiling of cell-free DNA from dogs with benign and malignant tumors.

OBJECTIVE: Cancer is currently the most common cause of death in adult dogs. Like humans, dogs have a one-third chance of developing cancer in their lifetime. We used shallow whole-genome sequencing (sWGS) to analyze blood cell-free DNA (cfDNA) from four tumor-bearing dogs (one with benign and three with malignant tumors) and 38 healthy dogs. RESULTS: Similar to the results observed in the healthy dogs, no copy number aberration (CNA) was detected in the dog with benign lipomas, and the distribution of cfDNA fragment size (FS) closely resembled that of the healthy dogs. However, among the three dogs diagnosed with malignant tumors, two dogs exhibited varying degrees and quantities of CNAs. Compared to the distribution of FS in the healthy dogs, the cancer dogs exhibited a noticeable shift towards shorter lengths. These findings indicated that CNA and FS profiles derived from sWGS data can be used for non-invasive cancer detection in dogs.

A REVIEW OF NEOPLASIA IN PROSIMIANS IN HUMAN CARE FROM 1995 TO 2022.

This retrospective study of neoplasia in prosimians in human care reports histologically diagnosed cases from the archives of a nondomestic species pathology service between 1995 and 2022, primarily submitted from zoological institutions. To date, the only prior retrospective study of neoplasia in prosimians, published in 2009, was conducted with cases from a single institution specializing in prosimian noninvasive research and care. In the present study, a total of 153 neoplasms from 109 individuals were identified in the pathology service archives. The most commonly affected species belonged to the Lemuridae (92/109, 84.4%), particularly ring-tailed lemurs (Lemur catta; 55/109, 50.5%), black-and-white ruffed lemurs (Varecia variegata; 19/109, 17.4%), and red ruffed lemurs (Varecia rubra; 14/109, 12.8%). The digestive (49/153, 32.0%), reproductive (35/153, 22.9%), and integumentary (30/153, 19.6%) systems were most commonly affected. Hepatocellular neoplasia was the most common neoplasm overall (35/153, 22.9%), with a large proportion of hepatocellular carcinoma (23/35, 65.7%), suggesting a possible predisposition to this tumor in prosimians. The findings support aggressive behavior of these tumors in prosimians, and a majority (13/23, 56.5%) of cases had evidence of metastasis at the time of submission. Mammary neoplasia was also common (25/153, 16.3%) and predominantly malignant (18/25, 72.0%), in contrast with previous literature, although metastasis was uncommonly reported. The most common integumentary neoplasms were papillomas (12/30, 40.0%), and one report identified squamous cell carcinoma arising directly from a squamous papilloma. Several tumor types are reported herein for the first time in prosimian species, to the authors' knowledge. A literature review identifying additional cases reported since 2009 is also reported. This study contributes a large number of prosimian neoplasia cases to the existing literature to help determine trends in zoological collections and to inform captive prosimian health management.

Diagnosis and Staging of Equine Neoplasia.

The diagnosis of neoplasia in the horse is both simple and extremely challenging, depending on the type of neoplasm and its location. Obtaining an accurate diagnosis of a neoplastic condition is key to formulating an appropriate treatment plan if possible or developing a palliative plan if curative treatment options do not exist. A combination of historical features, clinical examination findings, and diagnostic testing typically allow a working diagnosis of neoplasia to be made, with a definitive diagnosis requiring the identification of neoplastic cells in a sample or tissue.

Surgical Management of Equine Neoplasia.

Equine neoplasia poses challenges in surgical management owing to their diverse locations and potential for aggressive behavior. Surgical interventions aim for complete excision while minimizing cosmetic and functional impairments. Techniques such as laser ablation and electrochemotherapy offer minimally invasive options for accessible tumors. For deeper or larger masses, surgical excision with adequate margins remains the gold standard. Preoperative biopsy and imaging guides surgical planning, ensuring complete tumor removal while preserving vital structures. Close adherence to a strict surgical protocol to prevent seeding of tumor cells, and, where possible, appropriate skin reconstruction techniques will improve cosmesis and outcome.

Unusual Equine Tumors.

There are a number of unusual tumors in the horse. Gross tumor characteristics, anatomical location, and signalment may assist with identification. Clinical pathology is often unrewarding with non-specific findings, while fine needle aspirates may not obtain sufficient tissue material to confirm a diagnosis. Although regular staining of biopsy material may be sufficient, immunohistochemistry markers may be required, especially in less differentiated tumors. The prognosis is dependent on the type, location, tumor size as well as on metastatic spread. A selection of unusual and rare tumors that the clinician is more likely to encounter is discussed.

Chemotherapeutics in Equine Practice.

Chemotherapy is the treatment of cancerous cells through the use of cytotoxic drugs. Whilst the use of systemic (intravenous) chemotherapy in equine practice is generally limited to the management of lymphoma, cytotoxic drugs are commonly used in the treatment of accessible skin tumors, either by topical application in the form of ointments or injected intralesionally. These drugs should be employed with caution due to the risk of serious adverse effects. In addition, extreme caution should be followed when preparing, handling, administering, and disposing them, due to their carcinogenic, mutagenic, and teratogenic properties.

In sickness and health - a questionnaire based study regarding immune mediated diseases and neoplasia in Swedish Nova Scotia Duck Tolling Retrievers.

BACKGROUND: The Nova Scotia Duck Tolling Retriever (NSDTR) has previously been highlighted as a breed at risk for developing immune mediated diseases and cancer. The immune response is of great importance for the development of neoplastic disease and a dysregulated immune response may predispose to cancer. Two of the commonly seen immune mediated diseases in NSDTRs are immune mediated rheumatic disease (IMRD), which bears similarities to systemic lupus erythematosus (SLE) affecting humans, and steroid-responsive meningitis-arteritis (SRMA), which is a non-infectious inflammation of the meninges and the leptomeningeal vessels. The aim of this survey study was to investigate the lifetime prevalence of immune mediated diseases and tumors among Swedish NSDTRs based on owners' information. The study design was cross-sectional. A questionnaire was sent to 4102 persons who owned or had previously owned a NSDTR. The questions concerned information about the dog and its overall health status as well as specific diseases. RESULTS: The response rate was 30%, including 935 live NSDTRs, corresponding to approximately 20% of the current population registered in Sweden (n = 4564), and 177 dead dogs. The surveyed dogs were spread over different ages and sex and corresponded to the typical demographic profile of the general dog population. Of the 935 individuals that were alive, 28 dogs (3%) were reported as previously diagnosed with IMRD and 33 dogs (3.5%) were reported as previously diagnosed with SRMA, one dog was reported to have been diagnosed with both SRMA and IMRD. There were 129 dogs (14%) reported to have or have had a neoplasia of some kind. For the dead dogs (n = 177), almost 40% of the owners reported neoplasia as the main reason for death/euthanasia. CONCLUSION: This study reports an estimated lifetime prevalence of IMRD and SRMA, in the studied population of Swedish NSDTRs, of 3.0 and 3.5% respectively. In this study, 14% of the living dogs (n = 935) were reported to have a neoplasia of some kind and almost 40% of the deceased dogs (n = 177) were euthanized due to neoplasia or suspicion of it.

Approaches and methods to study wildlife cancer.

The last few years have seen a surge of interest from field ecologists and evolutionary biologists to study neoplasia and cancer in wildlife. This contributes to the One Health Approach, which investigates health issues at the intersection of people, wild and domestic animals, together with their changing environments. Nonetheless, the emerging field of wildlife cancer is currently constrained by methodological limitations in detecting cancer using non-invasive sampling. In addition, the suspected differential susceptibility and resistance of species to cancer often make the choice of a unique model species difficult for field biologists. Here, we provide an overview of the importance of pursuing the study of cancer in non-model organisms and we review the currently available methods to detect, measure and quantify cancer in the wild, as well as the methodological limitations to be overcome to develop novel approaches inspired by diagnostic techniques used in human medicine. The methodology we propose here will help understand and hopefully fight this major disease by generating general knowledge about cancer, variation in its rates, tumour-suppressor mechanisms across species as well as its link to life history and physiological characters. Moreover, this is expected to provide key information about cancer in wildlife, which is a top priority due to the accelerated anthropogenic change in the past decades that might favour cancer progression in wild populations.

Neoplastic and non-neoplastic diseases associated with feline leukaemia virus (FeLV) in cats in southern Brazil.

The objective of this study was to categorise diseases associated with FeLV infection in cats. A total of 154 cats were submitted to necropsy, histopathology exam and anti-FeLV immunohistochemistry (IHC), and 83 (50.9 %) were IHC FeLV-positive. The cats age means of 4.1 years, including 3.6 % kittens, 34.9 % junior, 37.4 % prime, 18.1 % mature, 2.4 % senior, 3.6 % unknown age. Neoplastic diseases were most prevalent with leukaemia and lymphoma being most predominant, followed by viral diseases, bacterial, trauma, degenerative, intoxications, parasitic, malformation and others. FeLV+ cats were 5.73 times more likely to be diagnosed with neoplasms than other diseases. The odds ratio (OR) of FeLV+ cats developing leukaemia (OR = 7.75) and lymphoma (OR = 6.75) was higher than other neoplasms. FeLV infection was more prevalent in the mixed breed, junior to prime, male, with neoplastic diseases, including leukaemia and lymphoma. Therefore, understanding the diseases associated with FeLV is of paramount importance in Brazil due to its high prevalence, and it may encourage the implementation of prophylactic measures to reduce its dissemination.

Paraneoplastic Syndromes in Horses.

This article discusses the reported paraneoplastic syndromes (PNSs) in horses, including the possible pathogenesis, diagnostic methods, and any treatment options. The more commonly reported PNSs in horses include cancer anorexia and cachexia, fever and increased acute phase protein concentrations, and hypercalcemia and monoclonal gammopathy. As these conditions can often be more commonly diagnosed in non-neoplastic conditions, the diagnosis of a PNS and the accompanying neoplasia can be challenging. As signs of a PNS may precede signs of the underlying neoplasia, it is important that the clinician be aware of the possible presence of a PNS.

Radiotherapy in Equine Practice.

Radiotherapy is a valuable treatment option for equine tumors that have a high rate of recurrence or where complete surgical resection may damage vital structures. Teletherapy, brachytherapy, and plesiotherapy have been used successfully for the treatment of a variety of tumors and locations in the horse. Radiobiology, treatment protocols, side effects, and patient management are reviewed, with a focus on linear accelerator-based teletherapy. There is evidence of good success rates for treatment of periocular sarcoids and squamous cell carcinoma but teletherapy treatment is often limited to tumors on the head and distal extremities.

Principles of Tumor Biology.

Cancer is disease of the genome. The Hallmarks of cancer are a way of thinking of cancer to help rationalize what occurs in this disease process. A solid tumor is a complex of normal and neoplastic cells, arising through an evolutionary process to survive and grow. By understanding how normal cellular mechanisms are subverted to promote cancer we can refine our approach to improve outcomes. It gives us opportunities to prevent some cancers and allowing earlier diagnosis. We can refine conventional diagnostic tools and give more accurate prognoses. It offers novel targets to improve treatment of cancers, allowing personalized medicine.

Immunohistochemistry Screening of Different Tyrosine Kinase Receptors in Canine Solid Tumors-Part I: Proposal of a Receptor Panel to Predict Therapies.

The use of tyrosine kinase inhibitors (TKI) has been growing in veterinary oncology and in the past few years several TKI have been tested in dogs. However, different from human medicine, we lack strategies to select patients to be treated with each TKI. Therefore, this study aimed to screen different tumor subtypes regarding TKI target immunoexpression as a predictor strategy to personalize the canine cancer treatment. It included 18 prostatic carcinomas, 36 soft tissue sarcomas, 20 mammary gland tumors, 6 urothelial bladder carcinomas, and 7 tumors from the endocrine system. A total of 87 patients with paraffin blocks were used to perform immunohistochemistry (IHC) of human epidermal growth factor receptor 2 (HER-2), epidermal growth factor receptors 1 (EGFR1), vascular endothelial growth factor receptor 2 (VEGFR-2), platelet derived growth factor receptor beta (PDGFR-ß), c-KIT, and extracellular signal-regulated kinase 1/2 (ERK1/ERK2). The immunohistochemical screening revealed a heterogeneous protein expression among histological types with mesenchymal tumors showing the lowest expression level and carcinomas the highest expression. We have demonstrated by IHC screening that HER2, EGFR1, VEGFR-2, PDGFR-ß and ERK1/ERK2 are commonly overexpressed in dogs with different carcinomas, and KIT expression is considered relatively low in the analyzed samples.

Translational History and Hope of Immunotherapy of Canine Tumors.

Companion dogs have served an important role in cancer immunotherapy research. Sharing similar environments and diets with humans, dogs naturally develop many of the same cancers. These shared exposures, coupled with dogs' diverse genetic makeup, make them ideal subjects for studying cancer therapies. Tumors like osteosarcoma, hemangiosarcoma, soft-tissue sarcoma, and non-Hodgkin lymphoma occur with greater frequency than their counterpart disease in humans. Canine brain tumors allow the study of therapy strategies with imaging, surgery, and radiotherapy equipment in veterinary patients with near-human geometry. Nonspecific immunostimulants, autologous and allogeneic vaccines, immune checkpoint inhibitors, and cellular therapies used in treating canine cancers have been tested in veterinary clinical trials. These treatments have not only improved outcomes for dogs but have also provided valuable insights for human cancer treatment. Advancements in radiation technology and the development of tools to characterize canine immune responses have further facilitated the ability to translate veterinary clinical trial results to human applications. Advancements in immunotherapy of canine tumors have directly supported translation to human clinical trials leading to approved therapies for patients with cancer around the world. The study of immunotherapy in dogs has been and will continue to be a promising avenue for advancing human cancer treatment.

Retrospective analysis of carboplatin-induced cumulative neutropenia in cancer-bearing dogs.

OBJECTIVE: To determine the clinical significance of performing repeated postchemotherapy CBC for cancer-bearing dogs receiving ≥ 4 carboplatin treatments. The secondary aim was to identify risk factors associated with cumulative carboplatin-induced neutropenia in those dogs. ANIMALS: 40 client-owned dogs diagnosed with cancer. METHODS: A retrospective study using medical records from a single academic institution during 2012 to 2023. Dogs that received ≥ 4 doses of carboplatin with pre- and postchemotherapy CBCs available were included. Signalment and possible risk factors were recorded. Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events was used for neutropenia grading. RESULTS: 40 dogs met the inclusion criteria, with a total of 206 prechemotherapy and 188 postchemotherapy CBC results available. The median carboplatin dosage was 300 mg/m2 (range, 200 to 300 mg/m2). The median interval between carboplatin administration and the postchemotherapy CBC was 10 days (range, 6 to 38 days). Eleven dogs developed a grade 2 or higher neutropenia, with 5 dogs developing multiple neutropenic events, for a total of 18 separate events (18/394). Only 2 of 18 neutropenic events were recorded at the 10- to 14-day postchemotherapy CBC. The yield of detecting neutropenia at a postchemotherapy CBC at any carboplatin chemotherapy after the second dose was < 1% (1/149). Dogs that developed neutropenia at the pre-2nd chemotherapy CBC had a significantly higher risk of developing another neutropenic event at subsequent prechemotherapy CBC (P < .001). CLINICAL RELEVANCE: The incidence of cumulative neutropenia after 4 to 6 doses of carboplatin is low in cancer-bearing dogs. If a grade 2 or higher neutropenia is observed at or before the second prechemotherapy CBC, the dog is at a higher risk of developing neutropenia following future treatments.

Hotspot Exon 15 Mutations in BRAF Are Uncommon in Feline Tumours.

BRAF is one of multiple RAF proteins responsible for the activation of the MAPK cell signalling cascade involved in cell growth, differentiation, and survival. A hotspot BRAFV600E mutation, in exon 15, was determined to be a driver in 100% hairy cell leukaemias, 50%-60% of human melanomas, 30%-50% of human thyroid carcinomas and 10%-20% of human colorectal carcinomas. The orthologous BRAFV595E mutation was seen in 67% and 80% of canine bladder transitional cell carcinomas and prostatic adenocarcinomas, respectively. Since veterinary and human cancers exploit similar pathways and BRAF is highly conserved across species, BRAF can be expected to be a driver in a feline cancer. Primers were developed to amplify exon 15 of feline BRAF. One hundred ninety-six feline tumours were analysed. Sanger sequencing of the 211 bp PCR amplicon was done. A BRAF mutation was found in one tumour, a cutaneous melanoma. The mutation was a BRAFV597E mutation, orthologous to the canine and human hotspot mutations. A common synonymous variant, BRAFT586T, was seen in 23% (47/196) of tumours. This variant was suspected to be a single nucleotide polymorphism. BRAF was not frequently mutated in common feline tumours or in tumour types that frequently harbour BRAF mutations in human and canine cancers. As is seen in canine cancer genomics, the mutational profile in feline tumours may not parallel the histologic equivalent in human oncology.

Neoplastic and non-neoplastic lesions in biopsy samples from pet rabbits in Hong Kong: a retrospective analysis, 2019-2022.

Rabbits are popular pets in the urban environment of Hong Kong, ranking third behind cats and dogs. Here we describe the frequency of neoplastic and non-neoplastic lesions in biopsies from pet rabbits submitted to the CityU Veterinary Diagnostic Laboratory between 2019 and 2022, comprising 247 tissue samples from 243 rabbits collected by veterinarians in 19 veterinary clinics. Among the 243 rabbits, there were 128 females (65 spayed), 114 males (54 castrated); sex information was not provided for 1 rabbit. The rabbit breeds included 45 Lionhead, 35 Dwarf, 14 Lop, 11 Dwarf Lop, 5 French Lop, 3 Angora, 2 Dutch, 2 Holland Lop, and 1 each of Netherland Dwarf, Velveteen, Mini Lop, and New Zealand White. The mean ages of rabbits with neoplastic and non-neoplastic lesions were 7.1 and 5.7 y, respectively. The most common neoplastic lesions were adenocarcinoma (26.4%), trichoblastoma (21.4%), sarcoma (9.4%), and thymoma (8.2%). The most common non-neoplastic lesion was uterine cystic endometrial hyperplasia (14.8%), followed by dermal abscess formation in the ventral abdomen or skin of the head (12.5%). Although a broad spectrum of other lesions was described, our findings in biopsies from pet rabbits in Hong Kong are consistent with those in other jurisdictions.

DR-70 (fibrinogen-fibrin degradation products) as a prognostic biomarker in dogs with neoplasms.

Fibrinogen-fibrin degradation products (DR-70) are derived from tumor cells or metastases. Our previous study reported the diagnostic values in dogs with tumors, but no research has yet to be conducted to establish DR-70 as a prognostic marker. Herein, we investigated changes in DR-70 concentrations and disease courses in dogs with tumors. Overall survival time (OST) analysis was performed in 195 dogs with tumors, stratified with a recommended cut-off (1.514 µg/mL). Continual DR-70 measurements were performed during the medical interventions of 27 dogs with neoplasms. Clinical conditions and medical records were retrospectively reviewed. According to a cut-off value, dogs with plasma DR-70 concentrations above 1.514 µg/mL had shorter survival rates than those with concentrations below this threshold. In cases with complete or partial remission in response to treatment, the DR-70 concentration was decreased compared with that at the first visit, whereas it was increased in patients with disease progression. Our study suggested that changes in DR-70 concentration can be used as a prognostic biomarker for canine neoplasms. Furthermore, increased plasma DR-70 levels might be associated with shorter survival, and DR-70 concentrations may reflect responses to medical intervention.