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.

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.

Investigation of Prognostic Value of Claudin-5, PSMA, and Ki67 Expression in Canine Splenic Hemangiosarcoma.

Splenic hemangiosarcoma (HSA) is a malignant tumor of endothelial cells that affects middle-aged and elderly dogs and is characterized by the formation of new blood vessels, commonly associated with necrotic and hemorrhagic areas. Despite its importance in veterinary medicine, few studies have identified markers with prognostic value for canine HSA. Thus, this study aimed to associate the clinicopathological findings (prostate-specific membrane antigen [PSMA], Claudin-5, and Ki67 gene and protein expression) with overall survival in HSA-affected patients. Fifty-three formalin-fixed and paraffin-embedded canine splenic HSA samples, previously diagnosed by histopathological examination, were used in this study. Claudin-5, PSMA, and Ki67 protein expression levels were evaluated by immunohistochemistry, and gene expression was evaluated by quantitative polymerase chain reaction. Claudin-5 protein overexpression was observed in patients with metastasis (p = 0.0078) and with stage III tumors compared to those with stage I and II tumors (p = 0.0451). In patients treated with surgery alone, low PSMA gene and protein expression (p = 0.05 and p = 0.0355, respectively) were associated with longer survival time. Longer survival time was observed in patients with a low Ki67 index (p = 0.0488). Our results indicate that Claudin-5 protein expression is associated with metastatic status, and PSMA gene and protein expression, and Ki67 index are associated with survival time.

Prognostic Value of Intratumoral Collagen Quantification in Canine Oral Melanomas.

The majority of the melanocytic neoplasms are considered malignant and highly metastatic. However, a subset of the melanocytic tumors has a more favorable prognosis and the identification of precise prognostic markers for this neoplasm may be useful to guide treatment. The collagen architecture and density have been shown to correlate with tumor progression in human breast cancer and canine mast cell tumors. The purpose of the present study was to investigate the prognostic value of the intratumoral collagen index (ICI) as an indicator of postsurgical survival and its relation with other prognostic markers for canine oral melanomas (OMs). Twenty-two cases were tested for intratumoral collagen density using Masson's trichrome stain and morphometry. No differences were found between dogs regarding survival. The ICI was not correlated with proliferative activity or nuclear atypia. The results presented herein indicate that the quantity of intratumoral collagen in canine OMs is not an efficient indicator of postsurgical survival. Complementary studies about the expression and activity of enzymes that are capable of degrading extracellular matrix (ECM) components are necessary.

Expressão de PRSS11, MTSS1, CLPTM1, SMYD2, NOTCH1 e RPL37A em fatias de carcinoma de mama de cadelas e correlação com resposta à doxorrubicina in vitro / Expression of PRSS11, MTSS1, CLPTM1, SMYD2, NOTCH1 and RPL37A in slices of bitch mammary cancer and correlation with response to exposure doxorubicin in vitro

Os tumores da glândula mamária constituem as neoplasias mais frequentes em cadelas e a doxorrubicina é uma das principais drogas quimioterápicas utilizadas no tratamento deste tipo de câncer. A quimioterapia neoadjuvante com doxorrubicina possibilita a redução do tumor e permite a avaliação da resposta ao tratamento quimioterápico in vivo. A procura por marcadores preditivos de resposta tem o objetivo de identificar as pacientes responsivas e não responsivas ao tratamento com o quimioterápico de modo a permitir a indicação de uma abordagem terapêutica específica para cada paciente. A expressão de alguns trios de genes, incluindo PRSS11, MTSS1 e CLPTM1 e, PRSS11, MTSS1 e SMYD2 em mulheres com câncer de mama que receberam tratamento neoadjuvante com doxorrubicina permitiu a classificação das pacientes em sensíveis e resistentes ao tratamento. Outros genes diferencialmente expressos entre amostras consideradas sensíveis e resistentes à doxorrubicina foram NOTCH1 e RPL37A. Avaliamos no presente trabalho se a expressão de trios de genes permitia a classificação de resposta ao tratamento quimioterápico em outro modelo, constituído por carcinoma de mama de cadela, mantido em cultura de tecido na forma de fatias e exposto à doxorrubicina in vitro. A cultura de fatias de tecidos permite a manutenção da interação epitélio-mesênquima e é considerado um modelo mais próximo ao observado in vivo. Foram obtidas amostras de tumor mamário de 38 pacientes caninas atendidas no Hospital Veterinário da Faculdade de Medicina Veterinária da Universidade Metodista de São Paulo (UMESP), em São Bernardo do Campo, durante a cirurgia de mastectomia. Os proprietários deram seu consentimento livre e esclarecido para a realização do estudo. A idade mediana das pacientes foi de 10,4 anos e, 55% e 18,4% destas pacientes eram animais sem raça definida (SRD) e da raça poodle, respectivamente. Oito pacientes haviam sido submetidas previamente à cirurgia de esterilização...

Mammary gland tumors are the most common neoplasias of bitches and doxorubicin is one the mainstay drugs used in their treatment. Neoadjuvant chemotherapy with doxorubicin not only reduces the primary tumor as well as allows an in vivo evaluation of tumor response. Predictive markers of response, if identified, might allow a tailored treatment of each patient. In women with breast cancer submitted to neoadjuvant chemotherapy with doxorubicin, expression of groups of three genes, including PRSS11, MTSS1 and CLPTM1 and PRSS11, MTSS1 and SMYD2, classified the patients in responsive and resistant. Other genes differentially expressed between responsive and non-responsive tumors were NOTCH1 and RPL37A. We have then evaluated whether the expression of trios of these genes could allow the classification of tumors according to their response to chemotherapy, in another animal model constituted by mammary carcinoma of bitches, cultured as tissue slices and exposed to doxorrubicin in vitro. Culture of tissue slices preserves epithelial-mesenchymal interactions, in a similar way to that observed in vivo. Tumor samples were obtained from 38 canine patients treated at Hospital Veterinaria da Faculdade de Medicina Veterinária da Universidade Metodista de São Paulo (UMESP), São Bernardo do Campo, during mastectomy. Animal owners gave their informed consent to this study. Median age of patients was 10,4 years and 55% and 18,4% of them were mixed and poodle breed, respectively. Eight patients were previously spayed. Patients were classified in clinical stage III (39,47%), II (28,9%), I (18,4%) and IV (pulmonary metastasis only) (13,1%). Carcinomas were classified as cystic-papillary (34,2%), tubular (34,2%), tubular-papillary (18,42%) and solid (10,52%). Tumors were sliced and cultured in the absence or in the presence of doxorubicin (1 uM) for 24 hours and response evaluation was performed by cell counting of treated and untreated samples...

Estudo in vivo de um sistema de liberaçäo de drogas constituído por hidroxiapatita e cisplatina / In vivo study drug release system of constitute for hydroxyapatite and cisplatin

Um sistema de liberaçäo constituído por hidroxiapatita e cisplatina foi testado em ratos para avaliaçäo da liberaçäo local e sistêmica do antineoplásico cisplatina. Os animais que receberam os implantes com a droga desenvolveram efeitos colaterais ao tratamento, sendo os mais comuns: anorexia, diarréia, epistaxe e necrose cutânea no sítio de implantaçäo; cerca de 45 por cento deste animais morreram, indicando intoxicaçäo. Amostras de sangue e dos tecidos hepático, renal e muscular de todos os animais pertencentes ao experimento foram submetidas à detecçäo das concentraçöes de cisplatina, revelando a cinética de liberaçäo da droga pelo sistema proposto.