Evaluation of the safety and feasibility of electrochemotherapy with intravenous bleomycin as local treatment of bladder cancer in dogs.

Local treatment of canine urothelial carcinoma (UC) of the bladder is a challenge. More than 90% of the cases invade the muscular layer, more than 50% develop on bladder sites with a difficult surgical approach and often requiring radical surgical procedures. This study aims to evaluate the safety and feasibility of electrochemotherapy (ECT) with intravenous bleomycin (BLM) as a local therapy for bladder UC. This prospective study included 21 dogs with spontaneous bladder UC. Regional/distant metastases and neoplastic infiltration of the serosa was considered the main exclusion criteria. We had no deaths during ECT or in the immediate postoperative period, and no suture dehiscence. Most dogs (19/21) developed mild adverse effects, whereas two dogs developed ureteral stenosis. Complete response (CR) was achieved in 62% of the cases (13/21), while partial response (PR) was achieved in 24% (5/21). The median survival and disease-free survival times were 284 and 270 days, respectively. Overall survival was significantly better in the dogs who achieved a CR. In conclusion, ECT was well-tolerated in dogs with UC, demonstrating its safety and feasibility. These data pave the way for new studies aimed at evaluating the effectiveness of ECT in canine bladder UC as a translational model for human disease.

Diagnosis, Prognosis, and Treatment of Canine Hemangiosarcoma: A Review Based on a Consensus Organized by the Brazilian Association of Veterinary Oncology, ABROVET.

Hemangiosarcoma is a mesenchymal neoplasm originating in the endothelial cells of blood vessels; they can be classified as non-visceral and visceral types. Non-visceral hemangiosarcomas can affect the skin, subcutaneous tissues, and muscle tissues; visceral hemangiosarcomas can affect the spleen, liver, heart, lungs, kidneys, oral cavity, bones, bladder, uterus, tongue, and retroperitoneum. Among domestic species, dogs are most affected by cutaneous HSA. Cutaneous HSA represents approximately 14% of all HSA diagnosed in this species and less than 5% of dermal tumors, according to North American studies. However, Brazilian epidemiological data demonstrate a higher prevalence, which may represent 27 to 80% of all canine HSAs and 13.9% of all skin neoplasms diagnosed in this species. Cutaneous HSA most commonly affects middle-aged to elderly dogs (between 8 and 15 years old), with no gender predisposition for either the actinic or non-actinic forms. The higher prevalence of cutaneous HSA in some canine breeds is related to lower protection from solar radiation, as low skin pigmentation and hair coverage lead to greater sun exposure. Actinic changes, such as solar dermatosis, are frequent in these patients, confirming the influence of solar radiation on the development of this neoplasm. There are multiple clinical manifestations of hemangiosarcoma in canines. The diagnostic approach and staging classification of cutaneous HSAs are similar between the different subtypes. The definitive diagnosis is obtained through histopathological analysis of incisional or excisional biopsies. Cytology can be used as a presurgical screening test; however, it has little diagnostic utility in cases of HSA because there is a high risk of blood contamination and sample hemodilution. Surgery is generally the treatment of choice for dogs with localized non-visceral HSA without evidence of metastatic disease. Recently, electrochemotherapy (ECT) has emerged as an alternative therapy for the local ablative treatment of different neoplastic types; the use of radiotherapy for the treatment of dogs with cutaneous HSA is uncommon. There is greater consensus in the literature regarding the indications for adjuvant chemotherapy in subcutaneous and muscular HSA; doxorubicin is the most frequently used antineoplastic agent for subcutaneous and muscular subtypes and can be administered alone or in combination with other drugs. Other therapies include antiangiogenic therapy, photodynamic therapy, the association of chemotherapy with the metronomic dose, targeted therapies, and natural products. The benefits of these therapies are presented and discussed. In general, the prognosis of splenic and cardiac HSA is unfavorable. As a challenging neoplasm, studies of new protocols and treatment modalities are necessary to control this aggressive disease.

Accuracy of B-mode ultrasound and ARFI elastography in predicting malignancy of canine splenic lesions.

The objective was to evaluate the accuracy of B-mode ultrasonography and ARFI elastography in detecting malignancy in canine splenic lesions. Thirty-seven spleens with abnormalities (16 benign and 21 malignant) from dogs of different breeds and ages were evaluated. Echogenicity, echotexture, organ length and height were evaluated using B-mode. By ARFI elastography, tissue stiffness was evaluated qualitatively (elastogram) and quantitatively (measuring the shear wave velocity-SWV). Lesions were classified as diffuse, focal or multifocal (cranial, medial or caudal portion) and comparisons of the SWV between the injured and non-injured areas were performed. In the B-mode, no features were associated to malignancy (P > 0.05). In the elastogram, 35 spleens were non-deformable and 2 deformable, having no association with malignancy. The greater SWV was observed in malignant lesions (3.4 ± 0.6 m/s), followed by areas free from alterations (2.1 ± 0.3 m/s) and benign lesions (1.7 ± 0.5 m/s), with difference between groups (P < 0.0001). It was found that a SWV > 2.6 m/s indicates malignancy of canine splenic lesions (sensitivity of 95%, specificity of 100%, PPV of 100%, NPV of 94% and accuracy of 97%), concluding that ARFI elastography is a promising technique for differentiating malignancy in these lesions.

Diagnosis, Prognosis and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors.

Mast cell tumors (MCTs) are hematopoietic neoplasms composed of mast cells. It is highly common in dogs and is extremely important in the veterinary oncology field. It represents the third most common tumor subtype, and is the most common malignant skin tumor in dogs, corresponding to 11% of skin cancer cases. The objective of this critical review was to present the report of the 2nd Consensus meeting on the Diagnosis, Prognosis, and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors, which was organized by the Brazilian Association of Veterinary Oncology (ABROVET) in August 2021. The most recent information on cutaneous and subcutaneous mast cell tumors in dogs is presented and discussed.

Malignancy prediction of cutaneous and subcutaneous neoplasms in canines using B-mode ultrasonography, Doppler, and ARFI elastography.

BACKGROUND: Cutaneous and subcutaneous neoplasms are highly prevalent in dogs, ranging from benign to highly aggressive and metastatic lesions. The diagnosis is obtained through histopathology, however it is an invasive technique that may take a long time to obtain the result, delaying the beginning of the adequate treatment. Thus, there is a need for non-invasive tests that can help in the early diagnosis of this type of cancer. The aim of this study was to verify the accuracy of B-mode ultrasonography, Doppler, and ARFI elastography to predict malignancy in cutaneous and subcutaneous canine neoplasms. In addition, we aim to propose an ultrasonography evaluation protocol and perform the neoplasms characterization using these three proposed techniques. RESULTS: Twenty-one types of specific neoplasm were diagnosed, and using B-mode, we verified the association between heterogeneous echotexture, invasiveness, presence of hyperechoic spots, and cavity areas with malignancy. An increased pulsatility was verified in malignant neoplasms using Doppler (cut-off value > 0.93). When using the elastography, malignancy was associated with non-deformable tissues and shear wave velocity > 3.52 m/s. Evaluation protocols were proposed associating 4, 5, 6, or 7 malignancy predictive characteristics, and characterization was done for all tumors with at least two cases. CONCLUSIONS: We concluded that ultrasonography methods are promising and effective in predicting malignancy in these types of tumors, and the association of methods can increase the specificity of the results.

VEGF Expression, Cellular Infiltration, and Intratumoral Collagen Levels after Electroporation-Based Treatment of Dogs with Cutaneous Squamous Cell Carcinoma.

Canine cutaneous squamous cell carcinoma (SCC) is the most common type of skin cancer in tropical countries and is generally associated with exposure to solar ultraviolet light. It has a low metastatic rate, and local treatments, such as electrochemotherapy (ECT), promote long-term control or even complete remission. This study aimed to evaluate pre- and post-ECT treatment expression levels of vascular endothelial growth factor (VEGF) and CD31, cellular infiltration, and intratumoral collagen levels in dogs with cutaneous SCC. A prospective nonrandomized clinical study was performed using dogs with spontaneous SCC treated with ECT. Eighteen lesions from 11 dogs were included in the study. The expression levels of VEGF and CD31; cellular infiltration; and intratumoral collagen levels, as determined by Masson's trichrome staining, were not significantly different from pre-treatment measurements on day 21 (p > 0.05). However, among cellular infiltration, the mixed subtype was correlated with better overall survival time when compared to lymphoplasmacytic and neutrophilic infiltration (p < 0.05). In conclusion, ECT had no effect on VEGF expression, cellular infiltration, or intratumoral collagen levels in dogs with cutaneous SCC at the time of evaluation, suggesting that early and late post-ECT-treatment phases should be considered.

Ultrasonographic assessment of renal perfusion in bitches with mammary carcinoma treated with long-term carprofen.

The aim of this study was to evaluate renal hemodynamics, routine clinical and laboratory parameters used to estimate renal function, and clinical evolution during six months in bitches with mammary carcinomas that underwent mastectomy and were treated (TG) or not (CG) with carprofen for three months after surgery. Twenty-six bitches with mammary carcinoma were equally distributed into TG that received carprofen 4.4 mg/kg/day for 90 days and CG that did not receive anti-inflammatory medication. Renal artery Doppler flowmetry, contrast-enhanced ultrasound (CEUS) of renal parenchyma, haematological, biochemical and clinical analyses were obtained once a month. These data were compared between groups and time via analysis of variance (ANOVA) in a completely randomized design with repeated measures (P < 0.05). On B-mode ultrasound, the area of the renal artery was greater (P = 0.0003) in the TG. Regarding laboratory findings, haematocrit and haemoglobin were similar in both groups, showing a significant and gradual increase after three months of treatment; MCV, MHC, and MCHC were increased (P < 0.05) and lymphocyte and band counts decreased (P < 0.05) in the TG. Regarding biochemical tests, ALT was the only parameter with a significant difference, being higher (P = 0.0272) in the treated group. It can be concluded that the use of carprofen for 90 days causes minimal changes in renal perfusion, erythrocyte parameters and ALT activity, and reduces the proportion of blood inflammatory cells. Therefore, use of this medication can be carried out safely in patients who require auxiliary cancer treatment.

Response dataset from canine extramedullary plasmacytoma treated with lipophobic drugs enhanced by electroporation.

Over the past 15 years, lipophobic drugs, such as bleomycin and cisplatin, have been used combined with electroporation, which promotes their uptake through the cell membrane. The present data describe general findings following electrochemotherapy and how plasmacytomas can respond to this technique. We will explain and illustrate specific outcomes during the remission process. The data presented here can be useful for researchers, veterinarians, and pet owners. Furthermore, the data could be useful for other cutaneous or oral tumors in which electrochemotherapy may be indicated. Interpretation of the data and outcomes may be found in the research article entitled "Outcome following curative-intent electrochemotherapy for extramedullary plasmocytoma in dogs - case reports ."

Outcome Following Curative-Intent Electrochemotherapy for Extramedullary Plasmocytoma in Dogs - Case Reports.

Plasma cell tumors can occur as solitary collections referred as extramedullary plasmocytoma (EMP). The present report describes four cases of EMP treated with a local nonthermal ablative approach. Four dogs were diagnosed with extramedullary plasmocytomas (EMP) in different body regions (oral cavity, digits, and lip). Since surgical excision was declined by the owners (maxillectomy; amputation or lip reconstruction), a curative-intent approach was indicated as solely treatment- electrochemotherapy (ECT). All the patients received ECT under general anesthesia using bleomycin intravenously (15,000 UI/m²) or cisplatin intratumorally (1mg/cm³). All dogs developed transitory ulceration and swelling one-week after procedure that completely healed within 30 days post-ECT. Complete remission was achieved in all cases and lasted for 515 (oral case), 695 (one digit), 90 (another digit case) and 240 (lip) days. These results suggested that ECT promoted remission in EMP cases being a possibility for local control in dogs affected by this disease.

Prognostic phenotypic classification for canine mammary tumors.

Mammary neoplasms are a heterogeneous form of disease, and in order to determine its course and biological features with more accuracy, investigations based on tumor phenotypes are required. The aim of the present study was to propose and validate a phenotypic classification for canine mammary tumors and to assess any association between clinicopathological characteristics, survival and prognosis. For the immunohistochemistry analysis, the primary antibodies against estrogen receptor-α, progesterone receptor, human epidermal growth factor receptor 2 (HER-2)/neu and E-cadherin were used. A total of 110 canine mammary tumors were investigated; 42 tumors were classified as luminal A, 41 as luminal B, 17 as triple-negative and 10 as HER-2-positive. The luminal A and B phenotypes were associated with improved prognosis, whereas HER-2positive and triple-negative tumors were more aggressive, and exhibited a significant association with the occurrence of metastasis, a worse Tumor-Node-Metastasis classification and shorter survival time (P<0.05). In addition, there were different levels of E-cadherin expression intensity observed among the four tumor profiles investigated. Luminal A and B phenotypes presented an upregulation of E-cadherin compared with the HER-2 positive and triple-negative phenotypes (P<0.05). From the results of the present study, the proposed immunohistochemical panel and phenotypic classification techniques could be useful diagnostic tools with a good technical applicability in veterinary oncology. The analysis of E-cadherin expression in the panel of tumor markers allowed a more accurate classification for determining the biological features of the mammary tumor.

Intranasal Osteosarcoma in a Dog-A Case Report.

Osteosarcoma is the most commonly reported bone tumor in dogs, typically affecting the axial and appendicular skeleton. Involvement of the paranasal sinuses and the nasal cavity is extremely rare. This report describes a 6-year-old, female, cross-breed dog presented with signs of 90 days duration and diagnosed with a mass located in the right nasal cavity. Radiography, rhinoscopy, and computed tomography findings suggested the presence of an intranasal tumor. Osteosarcoma in the nasal cavity was diagnosed based on histopathological examination and clinical and imaging findings. Survival time was 12 months from diagnosis.

Evaluación clínica, epidemiológica y terapéutica en 14 casos de carcinoma inflamatorio mamario canino / Clinical, Epidemiological and Therapeutic Evaluation in 14 Cases of Inflammatory Breast Cancer in Canines / Avaliação clínica, epidemiológica e terapêutica em 14 casos de carcinoma inflamatório mamário canino

Con el objetivo de evaluar los aspectos clínicos, edad, raza, presencia de metástasis, protocolo quimioterapéutico, utilización de inhibidores de COX-2 y sobrevida en caninas diagnosticadas con carcinoma inflamatorio, en el Hospital Veterinario de Uberaba (HVU), se realizó un análisis retrospectivo de las historias clínicas de 14 hembras caninas atendidas en el HVU entre julio de 2011 y julio de 2012, con diagnóstico de carcinoma inflamatorio mamario. Las razas acometidas fueron mestizo, poodle, terrier brasilero, teckel y pastor belga. Edad media: 11,1 años. En 7 animales fueron detectados focos de metástasis a distancia. De ellos 5 pacientes recibieron como único tratamiento inhibidores de COX-2 y apenas 4 recibieron tratamiento quimioterapéutico. El protocolo, constituido por piroxicam, ciclofosfamida, carboplatina y doxorrubicina, presentó el mayor tiempo de sobrevida (210 días). En conclusión, el carcinoma inflamatorio es una enfermedad de mal pronóstico, poco tiempo de sobrevida, y ocasiona alteraciones sistémicas que disminuyen la respuesta terapéutica. Aparentemente la modalidad terapéutica más indicada es la asociación de inhibidores de COX-2 y quimioterapéuticos; sin embargo, son necesarios estudios clínicos controlados para evaluar estas sugestiones.

With the aim of evaluating clinical aspects, age, breed, presence of metastasis, chemotherapeutical protocol, use of COX-2 inhibitors and survival rate in female dogs diagnosed with inflammatory carcinoma at the Hospital Veterinario de Uberaba (HVU), a retrospective analysis was performed on the medical records of 14 female dogs seen at HVU between July, 2011 and July, 2012 and diagnosed with inflammatory breast cancer. The breeds included were crossbred, poodle, Brazilian terrier, teckel and Belgian shepherd. Average age: 11.1 years. Outbreaks of distant metastasis were detected in 7 animals, out of which 5 patients received COX-2 inhibitors as sole treatment and only 4 received chemotherapeutical treatment. The protocol, constituted by piroxicam, cyclophosphamide, carboplatin and doxorubicin showed the highest survival time (210 days). In conclusion, inflammatory carcinoma is a disease of bad prognosis, short survival time and produces systemic alterations that reduce therapeutic response. Apparently, the most accurate therapeutic form is the association of COX-2 inhibitors and chemotherapeutics; however, controlled clinical studies are needed in order to evaluate these suggestions.

Com o objetivo de avaliar os aspectos clínicos, idade, raça, presença de metástase, protocolo químico-terapêutico, utilização de inibidores de COX-2 e sobrevida em caninas diagnosticadas com carcinoma inflamatório, no Hospital Veterinário de Uberaba (HVU), se realizou uma análise retrospectiva das histórias clínicas de 14 fêmeas caninas atendidas no HVU entre julho de 2011 e julho de 2012, com diagnóstico de carcinoma inflamatório mamário. As raças acometidas foram SRD, poodle, terrier brasileiro, teckel e pastor belga. Idade média: 11,1 anos. Em 7 animais foram detectados focos de metástase a distância. Deles, 5 pacientes receberam como único tratamento inibidores de COX-2 e apenas 4 receberam tratamento químico-terapêutico. O protocolo, constituído por piroxicam, ciclofosfamida, carboplatina e doxorrubicina, apresentou o maior tempo de sobrevida (210 dias). Em conclusão, o carcinoma inflamatório é uma doença de mal prognóstico, pouco tempo de sobrevida, e ocasiona alterações sistêmicas que diminuem a resposta terapêutica. Aparentemente a modalidade terapêutica mais indicada é a associação de inibidores de COX-2 e químico-terapêuticos; contudo, estudos clínicos controlados são necessários para avaliar estas sugestões.

Transmissible [corrected] dog cancer genome reveals the origin and history of an ancient cell lineage.

Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell lineage. It is a transmissible cancer that propagates naturally in dogs. We sequenced the genomes of two CTVT tumors and found that CTVT has acquired 1.9 million somatic substitution mutations and bears evidence of exposure to ultraviolet light. CTVT is remarkably stable and lacks subclonal heterogeneity despite thousands of rearrangements, copy-number changes, and retrotransposon insertions. More than 10,000 genes carry nonsynonymous variants, and 646 genes have been lost. CTVT first arose in a dog with low genomic heterozygosity that may have lived about 11,000 years ago. The cancer spawned by this individual dispersed across continents about 500 years ago. Our results provide a genetic identikit of an ancient dog and demonstrate the robustness of mammalian somatic cells to survive for millennia despite a massive mutation burden.

Estenose da fossa intercondilar após estabilização articular com retalho de fáscia lata em cães / Intercondylar fossa stenosis after joint stabilization using a fascial strip in dogs

Determinaram-se os índices de largura da fossa intercondilar (FI), após transecção do ligamento cruzado cranial em nove cães adultos submetidos à estabilização articular com retalho de fáscia lata. Os joelhos foram alocados em dois grupos, sendo o joelho direito (GI) submetido à incisuroplastia troclear (ITR) e posterior estabilização articular, e o joelho esquerdo submetido somente à substituição ligamentar (GC). Cada grupo foi dividido em três subgrupos correspondentes aos momentos de eutanásia aos 30, 90 e 180 dias de pós-operatório. Os índices de largura da FI foram determinados, macroscópica e radiograficamente, pela mensuração da abertura cranial da FI nos terços cranial, médio e caudal, e indexados em relação à largura epicondilar. Observou-se aumento significativo dos índices macroscópicos e radiográficos nas articulações do GI, sendo estes estatisticamente diferentes daqueles das articulações de GC. Não foi observada estenose intercondilar nos joelhos de GC após a estabilização articular. Conclui-se que a estabilização articular com retalho de fáscia lata preveniu a estenose da fossa intercondilar, e que a ITR promoveu o alargamento permanente dessa estrutura.

Intercondylar fossa width indexes (IFWI) were determined in nine adult dogs submitted to intercondylar notchplasty (IN) after transection of the cranial cruciate ligament (CCL) followed by a fascial strip stabilization. The right stifle was submitted to IN followed by fascial strip reconstruction of the CCL (GI) while in the left stifle IN was not performed (GC). Each group was then divided into three subgroups which corresponded to time of euthanasia at 30, 90 and 180 days after surgery. IFWI were determined, both macroscopically and radiographically, by measuring the cranial outlet of the intercondylar fossa in relation to the epicondylar width. A significant increase was observed in indexes of GI following IN, and these differed from indexes of GC throughout the evaluation period. It was concluded that articular repair using a fascia strip prevented stenosis of the intercondylar fossa, and that IN caused a permanent widening of it.

Neuropatia paraneoplásica associada ao mastocitoma canino / Paraneoplastic neuropathy associated with canine mast cell tumor

As síndromes paraneoplásicas compreendem um grupo diverso de alterações clínicas associadas a neoplasias e ocorrem em sítios distantes do tumor primário ou de suas metástases. As neuropatias paraneoplásicas são distúrbios raros em cães, mas representam morbidade significativa e servem como importantes indicadores diagnósticos e prognósticos. O presente trabalho relata a ocorrência de dois casos de neuropatia paraneoplásica em cães com mastocitoma, considerando a apresentação clínica, o diagnóstico e as formas de tratamento utilizadas.

Paraneoplastic syndromes comprise a diverse group of clinical anomalies associated with neoplasias and occur in a location distant from the primary tumor or of your metastasis. Paraneoplastic neuropathy are rare disturbs in dogs, but represent significant morbidity and are useful as diagnostic and prognostic indicators. This work report the occurrence of two cases of paraneoplastic neuropathy in dogs with mast cell tumor, considering the clinical signs, diagnosis and treatment used.

Effects of isoflurane on Tei-index of myocardial performance in healthy dogs.

Recently, the Tei-index, a noninvasive index that combines systolic and diastolic time intervals, has been proposed to assess global cardiac performance. However, the effects of isoflurane on the Tei-index have not been characterized. This study aimed at studying the effects of 1.0 minimal alveolar concentration isoflurane anesthesia on the pre-ejection period (PEP), left ventricular ejection time (LVET), PEP/LVET ratio, isovolumic relaxation time (IVRT), stroke index (SI), cardiac index (CI), heart rate (HR), and the Tei-index in healthy unpremedicated dogs. We observed significant increases in PEP, PEP/LVET ratio, IVRT, and TEI, whose maximal increases obtained throughout the study were 47%, 48%, 78%, and 56%, respectively. The LVET and HR did not change significantly, whereas the SI and CI decreased during anesthesia (29% and 26%, respectively). In conclusion, isoflurane produced direct effects on the Tei-index. The changes in systolic and diastolic parameters were supportive of this finding and were consistent with an overall impairment of left ventricular function during anesthesia.

Neoplasias de língua em cinco cães / Neoplasms of the tongue in five dogs

Este trabalho tem como objetivo relatar a ocorrência de cinco casos de neoplasias de língua em cães. Os sinais clínicos mais observados foram ptialismo, halitose e hiporexia. Após biópsia excisional para exame histopatológico, os resultados revelaram dois casos de melanoma, um caso de histiocitoma, um caso de fibrossarcoma e um caso de mastocitoma grau II, sendo que neste o proprietário não autorizou qualquer forma de tratamento. O tratamento para os demais foi a glossectomia parcial e, no caso de fibrossarcoma, associou-se a quimioterapia. Dois animais apresentaram deiscência de sutura no pós-operatório, não havendo necessidade da realização de nova intervenção. Em relação ao prognóstico, os pacientes com histiocitoma, fibrossarcoma e um com melanoma não apresentaram recidiva, nem metástase da doença 12 meses após a cirurgia. No outro caso de melanoma, o paciente apresentou metástase na pele e nos pulmões 30 dias após a ressecção cirúrgica.

This paper is aimed at reporting five cases of neoplasms of the tongue in dogs. The clinical signs most observed were ptyalism, halitosis and hyporexia. After excisional biopsy the histological findings revealed two cases of melanoma, one case of histiocytoma, one case of fibrosarcoma and one case of mast cell tumor grade II, but in this case the owner didn't authorize any form of treatment. The treatments for the others cases were the partial glossectomy, and in the fibrosarcoma's case the chemotherapy was associated. Two animals had suture deiscencia in the post operatory, but in these cases it wasn't necessary another surgery. About the prognostic, the patients with histiocytoma, fibrosarcoma and one with melanoma didn't present cancer recurrence either metastasis 12 months after the surgery. But in another melanoma case the patient presented skin and lungs metastasis 30 day after surgery.