The role of lymph nodes and their drainage in canine mammary gland tumours: Systematic review.

Mammary gland tumours are the most common neoplasms in intact bitches. Over the last decades, veterinary oncology has evolved in detecting and determining the lymph nodes to be removed in these patients for an accurate staging and prognosis, as well as to achieve better disease control and higher overall survival time. Our objective was to describe recent advances related to lymphatic drainage in bitches with mammary gland tumours, focusing on surgery, diagnosis, and prognosis. Through a systematic review using PubMed as the database, a thorough multi-step search reduced 316 studies to 30 for analysis. Vital dyes appear to be crucial in reducing the overall surgery time through transoperative staining of the lymph nodes. Imaging contrasts provide information regarding specific tumour drainage; however, there is still little evidence for their use. The axillary and superficial inguinal lymph nodes are well-established as regional lymph nodes of the cranial and caudal mammary glands. In sequence, accessory axillary, medial iliac, popliteal, and sternal lymph nodes should receive attention if they demonstrate contrast drainage, even considering that the literature has not shown a relationship between drainage and metastasis in these cases. In conclusion, recent studies have provided us with more support in regional lymph node excision regarding the TNM staging system. Studies are highly heterogeneous and method comparisons do not fit due to the non-uniformity of samples, materials, and procedures. We suggest further studies with a larger sample size, complete follow-up of patients, contrast use, and lymph node morphological and immunohistochemical analysis.

Comparison of Different Pneumorrhaphy Methods after Partial Pulmonary Lobectomy in Dogs.

Pulmonary loborraphy can be performed using manual sutures and staples, although other methods, such as tissue adhesives, are also cited in the veterinary literature. Although the surgery is well tolerated in the canine species, failure in pulmonary aerostasis is still a reality since all the methods described so far eventually lead to air leakage after the use of the partial lobectomy technique in the lungs. Within this context, the aim of this research was to compare the effectiveness of different hermetic sealing methods after partial lobectomy of the right caudal lung lobe (RCLL) in dogs. 30 cadavers models were divided in 6 groups: G1-cobbler suture associated with simple continuous; G2-overlapping continuous suture associated with simple continuous suture; G3-Ford interlocking suture; G4-Stapling device; G5-Tissue glue (cyanoacrylate). After performing the sealing techniques, the lungs were submerged in water and inflated with oxygen at positive ventilatory pressures at physiological (up to 14.7 mmHg, which is equivalent to up to 20 cmH2O) and supraphysiological levels (above 14.7 mmHg) to evaluate the performance of the sealing methods. At physiological ventilatory pressure levels, there was no difference between groups. Sealing with surgical glue was superior to interlocking sutures and stapling devices at supraphysiological levels of ventilatory pressure.

Molecular Profile of Canine Hemangiosarcoma and Potential Novel Therapeutic Targets.

Canine hemangiosarcoma (HSA) is a relatively common neoplasia, occurring mainly in the skin, spleen, liver and right atrium. Despite the numerous studies investigating the treatment of canine HSA, no significant improvement in survival has been achieved in the last 20 years. Advancements in genetic and molecular profiling presented molecular similarities between canine HSA and human angiosarcoma. It could therefore serve as a valuable model for investigating new and more effective treatments in people and dogs. The most common genetic abnormalities in canine HSA have been found in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and neuroblastoma RAS viral oncogene homolog (NRAS) pathways. Mutations are also found in tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN) and cyclin dependent kinase inhibitor 2A (CDKN2A). Known abnormal protein expression could be exploited to trial new target treatments that could be beneficial for both canine and human patients. Despite the high expression of vascular endothelial growth factor (VEGF) and its receptor (VEGFR), no correlation with overall survival time has ever been found. In this review, we explore the most recent developments in molecular profiling in canine HSA and discuss their possible applications in the prognosis and treatment of this fatal disease.

Comparison of surgical resection of Axillary Lymph Nodes in Dogs with Mammary Gland Tumors with or without sentinel lymph node visualization with patent blue dye.

Introduction: Dogs' axillary lymph node (ALN) is often difficult to locate before surgical resection. The anatomical location of ALN often discourages Veterinarians from surgical lymphadenectomy. Considering the limited literature available, the actual incidence of metastases and the prognostic relevance are poorly understood. Methods: A non-randomized, prospective clinical study was conducted with female dogs (n = 41) with mammary gland tumor (MGT) in the thoracic or cranial abdominal mammary glands. The study investigated the risks of ALN metastasis based on tumors clinical findings, tumor size, histopathological diagnosis and grade. The main aim of this study was to compare ALN resection with or without patent blue 2.5% (PB) dye injection for sentinel lymph node visualization. A total of 46 mastectomies were performed and five animals underwent two mastectomies. In the first group, 17 patients underwent a mastectomy and lymphadenectomy without PB injection (G1). In contrast, in the second group, 24 patients also received PB injections for sentinel lymph node mapping (G2). The ALN was identified in 38/46 cases (82%). The ALN was identified and excised in only 58% of surgeries in G1(19/46), while in group 2, the lymph node was identified in 92% of the cases and resected in 100% of the cases. The use of PB improves ALN's identification and reduces the surgical resection time in dogs with MGT. Results and discussion: Surgical time differed between the two groups, as it was significantly shorter in the PB injection group compared to group 1 (80 vs. 45 min) (p < 0.0001). The overall frequency of ALN metastasis was 32%. Macroscopic abnormalities in the lymph nodes, tumor size (>3 cm), and diagnosis of anaplastic carcinoma or grade II/III mammary gland tumors were associated with a higher probability of ALN metastasis. Metastases in the ALNs are more common, in dogs presenting with tumors larger than 3 cm and diagnosed with aggressive histological subtypes. The ALNs should be removed for correct staging, prognostic evaluation, and decision for adjuvant therapy.

Extreme lymphocytosis in a dog with T-zone lymphoma.

Background: Canine T-zone lymphoma (TZL) is recognized as an indolent CD45-T cell lymphoma, with low aggressiveness and high overall survival. The diagnosis is obtained by histopathology and immunohistochemistry, but also by cytological examination of the lymph node associated with immunophenotyping. Lymphocytosis is commonly identified as around 10,000 cells/µl and may reach 30,760 cells/µl. Case Description: The present report describes a case of a female Golden Retriever, nine years old, with generalized lymphadenopathy. In the cytological examination of the superficial cervical lymph node, a monomorphic population of small, "clear cells" and "hand mirror" lymphocyte shape was suggestive of TZL. The leukogram showed intense leukocytosis (160,050 cells/µl) due to small clear cell lymphocytosis (152,048 cells/µl). The myelogram showed a myeloid:erythroid ratio of 2:3; with a pyramidal distribution of cell types and the presence of 22.8% of lymphocytes in the differential count. Bone marrow, peripheral blood, and lymph node immunophenotyping resulted in lymphocyte gates with 97.3% to 99.5% CD5+, predominantly CD4-, CD8-, and CD45- confirming the diagnosis of TZL with associated leukemia. Treatment with chlorambucil and prednisolone was started. During the first month, the lymphocytosis remained above 200,000 cells/uL. After four months of treatment, there was a decrease in lymphocytes, which progressively reached a count of 10,800 cells/ul in the eleventh month. Conclusion: In the literature, lymphocytosis above 30,760 cells/µl has not been observed in TZLs. Thus, it is believed that this is the first report of extreme lymphocytosis with a slow response to chemotherapy.

Secretory carcinoma of the canine mammary gland with nodal and bone metastases: Case report.

Background: Secretory carcinoma is a rare histological type of breast neoplasm in humans and dogs that is characterized by the presence of intracellular and extracellular eosinophilic secretions. Case Description: In this case report, we describe the cytological, histological, and immunohistochemical characteristics of secretory mammary carcinoma in a 10-year-old mixed-breed female dog with nodal and bone metastases. The bitch had a history of claudication and a mass in the left humeral scapular region, which revealed osteolysis of the proximal humerus on radiography. Fine-needle aspiration cytology revealed numerous neoplastic cells arranged mostly in cohesive groups but sometimes isolated, that contained cytoplasmic vacuoles and had a moderate-to-high nucleus: cytoplasm ratio with frequent karyomegaly and evident nucleoli. Histologically, the neoplasm was organized in solid, tubular structures with luminal spaces filled with eosinophilic secretions and was composed of cells with clear cytoplasm and prominent vacuoles that pushed the nuclei to the periphery, resembling signet ring cells. The extracellular and intracytoplasmic material of the epithelial cells was positive for periodic acid-Schiff staining and immunoreactive for alpha-lactalbumin. Two chemotherapy sessions were performed, but 1 month after surgery, the clinical condition worsened, and euthanasia was elected, accounting for 133 days of survival after surgical removal of the tumor. Conclusion: The bitch presented with secretory mammary carcinoma with nodal and bone metastases, and histological and immunohistochemical characteristics were important for diagnosis. The morphological and immunohistochemical characteristics of this carcinoma were similar to those observed in humans. Mammary gland secretory carcinoma with bone metastasis must be included as a differential diagnosis among canine mammary gland carcinomas showing cellular morphological characteristics of intracytoplasmic vacuolization and eosinophilic secretion.

Retrospective study of retroviruses by immunoenzymatic test on cats in Grande Vitória (ES, Brazil) and associated neoplasms.

Retroviruses are among the leading causes of death in domestic cats. Retroviruses associate with the host cell in a persistent and permanent way, leading to diverse clinical conditions. The feline leukemia virus (FeLV) is the most pathogenic retrovirus with the potential to cause both degenerative diseases and immunosuppression, as well as proliferative diseases, as its association with the cell may lead to a direct oncogenic effect. The feline immunodeficiency virus (FIV), in turn, can lead to the classic immunodeficiency syndrome, usually has a chronic, less aggressive course and has no direct oncogenic effect. The use of vaccines and control measures has resulted in a decrease in the prevalence of FeLV in the United States of America (USA) and Europe, however, in Brazil, statistics show prevalence rates above 50%. This study aimed to assess the prevalence of feline retroviruses, by immunoenzymatic assay testing, in the region of Grande Vitória, in Espírito Santo and also point out the frequency of neoplasms in these cats. A total of 388 cats were retrospectively evaluated (2014-2016). The prevalence of FIV was 2.3% and FeLV was 33.7%. Neoplasms were identified in the three cats seropositive for FIV and FeLV and in three cats infected only with FIV. Neoplasms were also found in 26.6% of cats that were seropositive only for FeLV, especially mediastinal lymphoma. The high prevalence of FeLV demonstrated in this study highlights the need for establishing effective control measures, with emphasis on vaccination.

As retroviroses encontram-se entre as principais causas de morte em gatos domésticos. Os retrovírus associam-se à célula hospedeira de forma persistente e permanente, levando a quadros clínicos diversos. O vírus da leucemia felina (FeLV) é oretrovírus mais patogênico, com potencial para ocasionar tanto doenças degenerativas e imunossupressão, quanto doenças proliferativas, pois sua associação à célula pode levar ao efeito oncogênico direto. Já o vírus da imunodeficiência felina (FIV), pode levar à clássica síndrome de imunodeficiência, costuma ter um curso crônico, menos agressivo e não possui efeito oncogênico direto. O uso de vacinas e de medidas de controle resultaram em redução da prevalência de FeLV nos Estados Unidos da América (EUA) e Europa, entretanto, no Brasil, determinadas regiões podem apresentar prevalências superiores a 50%. Esse estudo teve como objetivo avaliar a prevalência das retroviroses felinas, pelo teste de ensaio imunoenzimático, na região da Grande Vitória, no Espírito Santo, apontando ainda, a frequência de neoplasias nesses gatos. Um total de 388 gatos foram retrospectivamente avaliados (2014-2016). A prevalência de FIV foi de 2,3% e de FeLV 33,7%. Neoplasias foram identificadas nos três gatos sororeagentes para FIV e FeLV e em três gatos infectados apenas por FIV. Constatou-se a presença de neoplasias ainda em 26,6% dos gatos sororeagentes apenas para FeLV, com destaque para o linfoma na forma mediastinal. A elevada prevalência de FeLV demonstrada neste estudo aponta sobre a necessidade da instituição de medidas efetivas de controle, com destaque para a vacinação.

Pancreatic cyst in a cat / Cisto pancreático em um gato

ABSTRACT: Pancreatic cysts are rare in both humans and animals. They are defined as an enclosed structure externally surrounded by a capsule, internally coated with a cuboidal epithelium and filled with liquid or semi-solid content. This case described the clinical and pathological characteristics of a pancreatic cyst in a feline. A mixed breed cat with a history of recurrent vomiting was attended. Physical examination revealed pain on abdominal palpation. Abdominal ultrasonography showed a cystic, anechoic structure with well-defined edges located in the left cranial abdomen and in close contact with the duodenum and pancreas. Partial pancreatectomy was performed. Microscopically, the structure was surrounded by fibrous material, coated with cuboidal to columnar epithelium, and containing eosinophilic material. Although, pancreatic cyst is rare in animals, they should be included in the differential diagnosis of causes of vomiting in young cats.

RESUMO: Os cistos epiteliais pancreáticos são raros em humanos e animais, e são definidos como estruturas encapsuladas rodeadas por epitélio cuboidal, preenchido por substância líquida. O objetivo desse estudo foi descrever as características clínico-patológicas de um cisto pancreático verdadeiro em um felino. Foi atendido uma gata sem raça definida com histórico de vômitos recorrentes. No exame físico o animal apresentou dor à palpação abdominal. Na ultrassonografia abdominal, evidenciou-se a presença de uma estrutura cística, anecóica e com bordos bem definidos localizado no abdome cranial esquerdo, em contato com o duodeno e o pâncreas. Foi realizada pancreatectomia parcial. No exame microscópico observou-se estrutura encapsulada, circundado por material fibroso, revestido por epitélio cuboidal a colunar, contendo material eosinofílico. Embora os cistos pancreáticos verdadeiros sejam raros nos animais, eles devem ser incluídos no diagnóstico diferencial de doenças que cursam com vômitos nos gatos.

Clinical, histological, immunohistochemical and genetic factors associated with measurable response of high-risk canine mast cell tumours to tyrosine kinase inhibitors.

The aim of the present prospective-retrospective study was to evaluate the response of high-risk canine mast cell tumours (MCTs) to tyrosine kinase inhibitors (TKIs) and to correlate this with prognostic factors. A total of 24 dogs presented with macroscopic cutaneous MCTs at disease stage II or III, and therefore, at high-risk of associated mortality, were included in the study and treated with masitinib (n=20) or toceranib (n=4). A total of 12/24 dogs achieved an objective response and the overall survival (OS) for all subjects was 113 days. Dogs responding to treatment had a significant increase in OS compared to non-responders (146.5 days vs. 47 days, P=0.02). Internal tandem duplications in exon 11 of the c-kit gene were identified in 6/24 cases. Ki67, KIT immunolabelling and c-kit mutation did not provide information regarding prognosis or prediction of response to TKIs in this population. Initial response to TKIs appears to be the most reliable prognostic factor for survival duration.

Renal injury in female dogs with pyometra / Injúria renal em cadelas com piometra

ABSTRACT: Pyometra is a common disease in intact female dogs and can cause glomerulopathy and tubular injury. This study aimed to evaluate kidney injury in female dogs with pyometra, as well as progression of the injury during treatment and the markers of this condition. This study analyzed 20 intact female dogs with both clinical and sonographic diagnosis of pyometra. Dogs were treated with intravenous fluids and antibiotics, and an ovariohysterectomy was performed. The following parameters were assessed at eight separate time points: blood pressure; serum creatinine, phosphorus, and urea levels; urinalysis and urinary biochemical parameters [urinary gamma-glutamyl transferase (uGGT) and urinary protein-to-creatinine ratio (UPCR)]; glomerular filtration rate (GFR); and urine output. All dogs showed some degree of kidney injury at the time of pyometra diagnosis. This was transient in most animals, resolving with treatment of the pyometra. Measurement of uGGT and UPCR identified renal parenchymal injury, helping to determine the prognosis of the animals analyzed in the present study.

RESUMO: A piometra é afecção frequente em cadelas e pode causar glomerulopatias e lesões tubulares. O presente estudo objetivou avaliar injúria renal em cadelas com piometra, sua progressão ao longo do tratamento e o uso de marcadores dessa alteração. Participaram 20 cadelas com diagnóstico clínico e ultrassonográfico de piometra, submetidas à fluidoterapia, antibioticoterapia e ovariohisterectomia. Foram avaliados pressão arterial, concentração sérica de creatinina, fósforo e ureia; urinálise e bioquímica urinária (gama-glutamiltransferase urinária e razão proteína/creatinina urinárias), taxa de filtração glomerular e débito urinário, em oito tempos. Todas as cadelas apresentaram algum grau de injúria renal no momento do diagnóstico da piometra, sendo transitória na maioria dos animais após o tratamento. O uso de marcadores de injúria renal identificou lesão de parênquima renal, contribuindo com o prognóstico dos animais estudados.

Cyclooxygenase-2 expression in epithelial neoplasms and its relevance as a targeted therapy in dogs / Expressão de ciclooxigenase-2 em neoplasias epiteliais e sua relevância como terapia alvo em cães

ABSTRACT: Targeted therapy of neoplasms is an emergent approach in human and veterinary medicine. Cyclooxygenase (COX) is a class of catalytic enzymes related to the formation of inflammatory mediators. COX-2 is expressed constitutively in a few body tissues, but it may be induced in specific pathophysiologic conditions, such as cancer. COX-2 expression in neoplams may be considered a potential predictive factor, due to the possible association of selective COX-2 inhibitors in adjuvant treatments. This scientific communication has the objective to report COX-2 expression in seven neoplasms of dogs and the usage of adjuvant treatment with COX-2 selective inhibitors as an effective and feasible option in cancer treatment.

RESUMO: O tratamento direcionado das neoplasias é uma abordagem emergente tanto na medicina humana, quanto na veterinária. A cicloxigenase (COX) é uma classe de enzimas catalíticas relacionada à formação de mediadores inflamatórios. A COX-2é expressa de forma constitutiva em poucos tecidos, mas pode ser induzida em condições patofisiológicas específicas, como os processos neoplásicos. A expressão da COX-2 em neoplasias pode ser considerada um fator preditivo em potencial, tendo em vista a possibilidade de associação de inibidores seletivos para COX-2 em tratamentos adjuvantes. Esta comunicação científica teve como objetivo relatar a expressão de COX-2 em neoplasias de sete cães e o tratamento adjuvante com inibidores seletivos para COX-2 como uma opção efetiva e viável no tratamento do câncer.

Fatores prognósticos e preditivos dos tumores caninos definidos com auxílio da imuno-histoquímica / Prognostic and predictive factors of canine tumours defined with immunohistochemistry's assistance

A imuno-histoquímica pode ser aplicada na oncologia veterinária para a definição do imunofenótipo neoplásico, com possibilidades ilimitadas de utilização. A técnica baseia-se na identificação de antígenos "in situ", que podem apresentar valor prognóstico e terapêutico. A expressão de receptores de estrógeno e progesterona está diretamente relacionada ao melhor prognóstico para os neoplasmas mamários, enquanto a super-expressão do receptor KIT (CD117), proteínas Ki-67 (MIB-1), VEGF, CD31 e COX-2 podem ser associados à progressão tumoral para vários tipos histológicos. Essa associação possui valor preditivo em potencial, tendo em vista a possibilidade da utilização de bloqueadores específicos. Esta revisão tem como objetivo apresentar as possibilidades da utilização da imuno-histoquímica nos tumores de cães, visando à definição mais precisa do prognóstico e a indicação de tratamentos específicos para cada paciente.

Immunohistochemistry can be applied in veterinary oncology to define the immunophenotype of neoplastic cells with unlimited possibilities of application. The technique is based on the identification of antigens "in situ", which may have prognostic and therapeutic value. Expression of estrogen and progesterone is directly related to better prognosis for breast cancer, while over-expression of receptor KIT (CD117) proteins Ki-67 (MIB-1), COX-2, VEGF and CD31 can be associated with tumor progression for several histological types. This association has a potential predictive value, due to the possibility of using specific blockers. This revision aims at presenting the possibilities of immunohistochemical's application in tumors of dogs, searching for a more precise definition of the prognosis and indication of specific treatments for each patient.