Estudo prospectivo de neoplasias mamárias em gatas : métodos de avaliação dos linfonodos regionais e avaliação de comorbidades e de complicações associadas ao tratamento cirúrgico e adjuvante

O Carcinoma Mamário é altamente invasivo e metastático em gatas, por isso a sua detecção precoce e uma terapia agressiva podem influenciar no tempo de sobrevida global das pacientes. Ao mesmo tempo, são pacientes idosas com comorbidades importantes que necessitam ser diagnosticadas e estabilizadas antes do tratamento com complicações também importantes. Além disso, a imagem ultrassonográfica dos linfonodos axilares e inguinais durante o estadiamento clínico pode auxiliar no diagnóstico precoce das metástases regionais dessa neoplasia. O objetivo deste estudo foi acompanhar prospectivamente as gatas com neoplasias mamárias atendidas no Hospital de Clínicas Veterinárias (HCV/UFRGS) desde o diagnóstico até o tratamento cirúrgico e quimioterápico para: (1) descrever suas comorbidades e as complicações do tratamento cirúrgico e quimioterápico; (2) comparar a avaliação clínica, a imagem ultrassonográfica e a avaliação histopatológica dos linfonodos axilares e inguinais. Foram incluídas no estudo as gatas acometidas por neoplasias mamárias palpáveis, cujos tutores concordaram com a participação no estudo (CEUA/UFRGS - 32.717). As pacientes foram encaminhadas a atendimento clínico pelos métodos normais de triagem do HCV-UFRGS entre janeiro de 2017 e dezembro de 2018. Durante as avaliações clínicas para estadiamento das pacientes (ultrassom abdominal total, radiografias torácicas, urinálise, urocultura, hemograma e bioquímica sérica), foram realizados exames clínicos com palpação dos linfonodos axilares e inguinais, e exames ultrassonográficos dos mesmos. Após as linfadenectomias axilares e inguinais juntamente com mastectomias laterais ou bilaterais, foram realizadas as avaliações histopatológicas das neoplasias e dos linfonodos. Foram acompanhadas prospectivamente 34 gatas, 91% delas com neoplasias mamárias malignas, 13% já com metástase em linfonodos e 18% com metástase à distância no momento do diagnóstico. Com idade media de dois anos (0,5 - 8 anos), a maioria (29, 85%) não apresentava raça definida. Apenas 24 (71%) eram castradas, e dessas, apenas seis (18%) foram castradas antes de um ano de idade. Quinze (44%) receberam aplicação de progestágenos para prevenção de prenhez. Foram classificadas quanto ao estadiamento clínico,: 10 (29%) em estadio I; sete (21%), em II; 10 (29%), em III; e sete (21%), em IV. Os tratamentos realizados foram: mastectomia lateral (11,32.35%), mastectomia bilateral (4, 11.76%), mastectomia lateral e quimioterapia (4, 11.76%), tratamento paliativo e posterior eutanásia (4, 11.76%), biopsia excisional (3, 8.82%), eutanásia no momento do diagnóstico (3, 8.82%), quimioterapia e eutanásia (2, 5.88%), biopsia excisional e posterior mastectomia lateral (1, 2.94%), mastectomia com esplenectomia (1, 2.94%). Uma paciente foi a óbito antes de iniciar o tratamento. Os tipos histológicos com maior ocorrência foram os carcinomas: cribriforme (11, 32%), tubulopapilar (9, 27%), e tubular (2, 6%). Doze gatas (35%) apresentaram neoplasias com grau histológico III, seis (18%) apresentaram grau II, e seis (18%), grau I. O exame ultrassonográfico dos linfonodos (n=23) apresentou forte concordância (κ=0,805, p<0,000) no teste de Kappa (Software SPSS v.22, SPSS Inc., Chicago, USA) com o exame histopatológico, enquanto a palpação apresentou concordância razoável (κ=0,393, p=0,020). Cinco (22%) das 23 pacientes apresentaram invasão do linfonodo axilar, sete, (30%) do inguinal e uma (4%) apresentou invasão dos dois linfonodos. Foi possível verificar a associação (Teste Qui-Quadrado) entre a invasão dos linfonodos e ocorrência de ulceração (p=0,011), aderência (p=0,014), falta de delimitação (p=0,002), invasão linfática (p<0,001) e grau histológico (p<0,001). Vinte e duas gatas (65%) apresentavam Doença Renal Crônica (DRC) IRIS estágio 1, três gatas (9%) eram DRC 2, e três (9%) DRC 3. Outras comorbidades encontradas foram: cistite inflamatória (6, 17%), doença ortopédica degenerativa (6, 17%), Tríade Felina (4, 12%), pancreatite (3, 9%), Doença Inflamatória Intestinal (2, 6%), colangio-hepatite (2, 6%) hepatite (1, 3%), Cardiomiopatia Hipertrófica (1, 3%), e Adenocarcinoma biliar extra-hepático adenocarcinoma (1, 3%). Apenas quatro (12%) gatas iam ao veterinário periodicamente, e apenas duas tutoras palpavam as glândulas mamárias das gatas periodicamente.Mammary Carcinoma is highly invasive and metastatic in cats, so its early detection and aggressive therapy may influence the survival time of the patients. At the same time, they are elderly patients with important comorbidities who need to be diagnosed and stabilized prior to treatment with important complications. In addition, the ultrasonographic image of axillary and inguinal lymph nodes during clinical staging may help in the early diagnosis of regional metastases of this neoplasia. The objective of this study was to prospectively monitor cats with breast neoplasias treated at the Hospital de Clínicas Veterinárias (HCV / UFRGS) from diagnosis to surgical and chemotherapy treatment to: (1) describe their comorbidities and the complications of surgical and chemotherapy treatment; (2) to compare the clinical evaluation, the ultrasonographic image and the histopathological evaluation of the axillary and inguinal lymph nodes. The study included cats affected by palpable breast cancer, whose guardians agreed to participate in the study (CEUA / UFRGS - 32,717). The patients were referred to clinical care by the normal screening methods of HCV-UFRGS between January 2017 and December 2018. During the clinical evaluations for staging of the patients (total abdominal ultrasound, thoracic radiographs, urinalysis, uroculture, blood count and serum biochemistry), clinical examinations were performed with palpation of the axillary and inguinal lymph nodes, as well as ultrasound examinations of the same. After axillary and inguinal lymphadenectomies accompanied by lateral or bilateral mastectomies, histopathological evaluations of neoplasies and lymph nodes were performed. Thirty-four cats were prospectively followed, 91% of them with malignant mammaries neoplasms, 13% with lymph node metastasis and 18% with distant metastasis at diagnosis's time. With an average age of two years (0.5 - 8 years), the majority (29, 85%) had no defined race. Only 24 (71%) were castrated, and of these, only six (18%) were castrated before one year of age. Fifteen (44%) received progestogen application to prevent pregnancy. They were classified according to clinical staging: 10 (29%) in stage I; seven (21%) in II; 10 (29%) in III; and seven (21%) in IV. The treatments were lateral mastectomy (11, 32.35%), bilateral mastectomy (4, 11.76%), lateral mastectomy and chemotherapy (4, 11.76%), palliative treatment and subsequent euthanasia (4, 11.76%), excisional biopsy (3, 8.82%), euthanasia at the time of diagnosis (3, 8.82%), chemotherapy and euthanasia (2, 5.88%), excisional biopsy and later lateral mastectomy (1, 2.94%), mastectomy with splenectomy (1, 2.94%). One patient died before starting treatment. The most frequent histological types were carcinomas: cribriform (11, 32%), tubulopapillary (9, 27%), and tubular (2, 6%). Twelve cats (35%) presented neoplasms with histological grade III, six (18%) presented grade II, and six (18%), grade I. Ultrasound examination of the lymph nodes (n = 23) showed a strong concordance (κ = 0.805, p <0.000) in the Kappa test (SPSS Software v.22, SPSS Inc., Chicago, USA) with histopathological examination, while palpation presented reasonable agreement (κ = 0.393, p = 0.020). Five (22%) of the 23 patients presented invasion of the axillary lymph node, seven (30%) of the inguinal and one (4%) presented invasion of the two lymph nodes. It was possible to verify the association (Chi-square test) between the invasion of the lymph nodes and the occurrence of ulceration (p = 0.011), adherence (p = 0.014), lack of delimitation (p = 0.002), lymphatic invasion (p <0.001) and histological grade (p <0.001). Twenty-two cats (65%) had Chronic Kidney Disease (CKD) IRIS stage 1; three cats (9%) were classified as CKD 2, and three (9%) CKD 3. Other comorbidities founded was: inflammatory cystitis (6, 17%), degenerative orthopedic disease (6, 17%), Feline Triad (4, 12%), pancreatitis (3, 9%), Inflammatory Bowel Disease (2, 6%), cholangio-hepatitis (2.6%), Hepatitis (1, 3%), Hypertrophic Cardiomyopathy (1, 3%) and extrahepatic biliary adenocarcinoma (1.3%). Only four (12%) female cats went to the veterinarian periodically, and only two tutors periodically palpated the female mammary glands

Stem cells to improve the wound healing

The cellular therapy using Mesenchymal Stem Cells, specially its two subtypes - Bone-marrow Mesenchymal Stem Cells and Adipose Derived Stem Cells - can benefit by virtue of the possibility of differentiating in specialized cells that secrete and suppress growing factors and cytokines necessary in the lesion niche. When attracted by the pro-inflammatory sinalization of the lesion, they act using the paracrine signaling, decreasing the inflammation, increasing the angiogenesis and the cell migration and proliferation. The development in the researches regarding the association of the application of MSCs, with reconstructive surgery practices, leads to effective future results that can bring more benefits to the clinic practice of this field. This paper has the objective of briefly reviewing the literature about the usage of MSCs and its subtypes, the ADSCs, to improve the skin cicatrization

Clinical and Nutritional Follow-up of Cats with Chronic Kidney Disease Fed with a Renal Prescription Diet

Background: The use of prescription diets for cats with chronic kidney disease (CKD) is one of the main management approach of this disease in cats, and is considered a renoprotective strategy that may promote increased survival and/or improve quality of life, according to the stage of CKD. Besides that, nutritional assessment is important to monitor the maintenance of quality of life of the patients and their response to disease, especially those with chronic conditions. The aim of this study was to follow the clinical and nutritional status of cats with chronic kidney disease (CKD) IRIS stages II, III and IV fed with a renal prescription diet, followed for 12 months. Materials, Methods &amp; Results: Patients were fed exclusively with a dry renal prescription diet and medications for the management of CKD were prescribed when needed. Exclusion criteria were cats that already received a renal prescription diet or medications for the treatment of CKD. Cats were evaluated every 2 months, considering body weight (BW), body condition score (BCS), muscle mass score (MMS), clinical and laboratory parameters. In all assessments, a complete blood count and biochemistry were performed by conventional methods with the patient fasted for 12 h. In addition, urinalysis, urinary protein:creatinine ratio (UPC) and urine culture were performed from a urine sample collected by cystocentesis. The quantitative variables were tested for their stability on consecutive assessments using the non-parametric Friedman test, and did not present significant variation during follow-up, except for systolic blood pressure (SBP). Eight cats with a diagnosis of CKD were included in the study and 6 of them remained in the same CKD stage during follow-up. On cat died due to an unrelated CKD cause. Regarding nutritional assessment, 5 of 7 cats maintained BW during the 12 months. Of these, 4 also maintained MMS and BCS. Three of 7 cats presented a decrease in MMS, 2 of which presented also a decreased BW and one maintained BW.Discussion: IRIS staging results combined with Friedman’s analysis demonstrated that the diet and the clinical management were effective in the non-progression of CKD in this study. As renal injury is not expected to be reversed in CKD, the maintenance of cats in the same IRIS stages and the minimum variation of the parameters is considered a positive result in this study. Hypertensive cats started on antihypertensive therapy during the study, achieving adequate control of SBP in most cases, what can justify the variation of this clinical parameter over the 12 months. Hyperphosphatemia was a frequent alteration, included stage II cats, and presented a positive response to nutritional and medical therapy. Despite CKD staging progression was not observed in most cats using serum creatinine as a single parameter, some cats presented BW and MMS reduction, which may have influenced this result. Weight loss and muscle wasting may have occurred by several reasons, including periods of hyporexia, presence of concomitant diseases, aging process or reduced protein content on renal prescription diets. This study enhances the importance of the association of clinical and nutritional management in the maintenance of cats with CKD. We suggest that other studies are done during longer periods of time and with a larger sample to support the results found. We also suggest new studies to evaluate the protein requirements for cats with CKD

Clinical and nutritional follow-up of cats with chronic kidney disease fed with a renal prescription diet

Background: The use of prescription diets for cats with chronic kidney disease (CKD) is one of the main management approach of this disease in cats, and is considered a renoprotective strategy that may promote increased survival and/or improve quality of life, according to the stage of CKD. Besides that, nutritional assessment is important to monitor the maintenance of quality of life of the patients and their response to disease, especially those with chronic conditions. The aim of this study was to follow the clinical and nutritional status of cats with chronic kidney disease (CKD) IRIS stages II, III and IV fed with a renal prescription diet, followed for 12 months. Materials, Methods & Results: Patients were fed exclusively with a dry renal prescription diet and medications for the management of CKD were prescribed when needed. Exclusion criteria were cats that already received a renal prescription diet or medications for the treatment of CKD. Cats were evaluated every 2 months, considering body weight (BW), body condition score (BCS), muscle mass score (MMS), clinical and laboratory parameters. In all assessments, a complete blood count and biochemistry were performed by conventional methods with the patient fasted for 12 h. In addition, urinalysis, urine protein:creatinine ratio (UPC) and urine culture were performed from a urine sample collected by cystocentesis. The quantitative variables were tested for their stability on consecutive assessments using the non-parametric Friedman test, and did not present significant variation during follow-up, except for systolic blood pressure (SBP). Eight cats with a diagnosis of CKD were included in the study and 6 of them remained in the same CKD stage during follow-up. On cat died due to an unrelated CKD cause. Regarding nutritional assessment, 5 of 7 cats maintained BW during the 12 months. Of these, 4 also maintained MMS and BCS. Three of 7 cats presented a decrease in MMS, 2 of which presented also a decreased BW and one maintained BW. Discussion: IRIS staging results combined with Friedman’s analysis demonstrated that the diet and the clinical management were effective in the non-progression of CKD in this study. As renal injury is not expected to be reversed in CKD, the maintenance of cats in the same IRIS stages and the minimum variation of the parameters is considered a positive result in this study. Hypertensive cats started on antihypertensive therapy during the study, achieving adequate control of SBP in most cases, what can justify the variation of this clinical parameter over the 12 months. Hyperphosphatemia was a frequent alteration, included stage II cats, and presented a positive response to nutritional and medical therapy. Despite CKD staging progression was not observed in most cats using serum creatinine as a single parameter, some cats presented BW and MMS reduction, which may have influenced this result. Weight loss and muscle wasting may have occurred by several reasons, including periods of hyporexia, presence of concomitant diseases, aging process or reduced protein content on renal prescription diets. This study enhances the importance of the association of clinical and nutritional management in the maintenance of cats with CKD. We suggest that other studies are done during longer periods of time and with a larger sample to support the results found. We also suggest new studies to evaluate the protein requirements for cats with CKD

Treatment of canine multicentric lymphoma through vascular access port vs. peripheral venous catheter

Background: Vascular access port (VAP) was developed for the administration of chemotherapeutic agents, minimizing local drug reactions and complications associated with migration of peripheral venous catheter (PVC) in humans. The device is widely used in human oncology and has gained importance in veterinary oncology, especially in long treatment regimens, as in the case of canine lymphoma. VAP favors therapy and the animals life quality. The aim of this study was to describe the use of VAP in dogs, comparing to PVC access, during canine lymphoma chemotherapeutic treatment. Materials, Methods & Results: Eleven dogs with multicentric lymphoma which required chemotherapy were selected for the study. The dogs were randomly allocated to two groups with five and six animals, and each group received the chemotherapy protocol through the PVC (n= 5) or VAP (n= 6). For the sake of standardization, assessments were made whenever the dogs received vincristine sulfate, despite the use of the infusion system in all sessions of the Madison- Wisconsin protocol. A VAP was implanted into the right external jugular vein of six dogs under inhalational anesthesia, using the Seldinger technique. Systolic blood pressure (SBP) levels and handling time during chemotherapy sessions were compared in both groups in three time periods during the procedures: 10 min after arrival to each chemotherapy (P1); immediately after placement of the PVC or puncture of the VAP reservoir (P2); and at the end of chemotherapy (P3). The arithmetic mean of five consecutive assessments was used in each time period. In the chemotherapy sessions, the mean of SBP variation decreased statistically significant in the VAP group compared to PVC group. SBP decreased from P1 to P2 and from P1 to P3 in all sessions (S1, S2, and S3) in the VAP group, and increased in the PVC group. The handling time of VAP group was 110.6 ± 8.4 s, compared to 219.2 ± 24.7 s (mean ± standard error) in the PVC group, showing statisti¬cally significant difference (P < 0.001). VAP surgical implantation time averaged 37 min, decreasing gradually from the first (55 min) to the last patient (21 min). Discussion: SBP levels suggest that the VAP group was calmer from the beginning to the end of the sessions, showed lower SBP levels, and required shorter handling time than did the PVC group. Blood pressure is one of the most objec¬tive ways to assess welfare or stress in dogs. When dog feels threatened or scared, its body automatically enters a state of emergency and, among several changes, blood pressure increases. VAP surgical implantation in dogs have easy learning, as previously described, proven by implantation time progressive reduction. The Seldinger technique is the method of choice for catheter implantation in humans. Dissection of the jugular vein is an alternative, however, the technique with a single incision and venipuncture is less invasive than its modifications. The jugular vein was used because is the site of choice for central accesses in veterinary practice, with a shorter path to the right atrium and smaller rates of catheter mis¬placement, reducing the risk of pneumothorax, venous thrombosis, and pinch-off syndrome. VAP surgical implantation in dogs have easy learning, proven by the implantation time progressive reduction. The study confirmed that VAP promoted animal welfare, shortened chemotherapy sessions, and caused less discomfort to dogs treated for multicentric lymphoma, as indicated by the reduction in SBP, when compared to the PVC group

Mesenchymal stem cells applied to the inflammatory and proliferative phases of wound healing

A cicatrização de feridas é um processo que requer a interação de várias células da derme e epiderme. O objetivo deste trabalho foi avaliar qual o momento da aplicação das células das ADSCs em feridas cutâneas agudas que faria diferença na cicatrização nos primeiros sete dias da lesão. As células-tronco foram isoladas do tecido adiposo de camundongos C57Bl/6 GFP+. Para tanto, foram utilizados 49 camundongos C57Bl/6, divididos em quatro grupos: grupo I (GI/controle; n=14); grupo II (GII; n=14): ADSCs injetadas no d0; grupo III (GIII; n=14): ADSCs injetadas no terceiro dia; e Grupo IV (GIV; n=7): ADSCs injetadas no quinto dia. As avaliações clínicas ocorreram nos dias zero, três, cinco e sete, e as histopatológicas nos dias cinco e sete. Na metodologia proposta, foi observado que o uso de ADSCs aumenta a vascularização, a formação de tecido de granulação, a colagenização e incrementa o número de folículos pilosos em apenas sete dias de avaliação. Além disso, o momento da aplicação das células não repercutiu diferenças significativas nas fases inflamatória e proliferativa do processo de cicatrização das feridas cutâneas.Wound healing is a process that requires the interaction of various cells in the dermis and epidermis. The aim of this study was to evaluate the action of ADSCs in the treatment of acute wounds in order to understand if application time of the cells results in a difference in healing the first seven days of injury. The stem cells were isolated from adipose tissue of C57BL / 6 mice GFP +. Thus, we used 49 mice C57BL / 6 divided into four groups: Group I (GI / control, n=14); Group II (GII; n=14): ADSCs injected to the d0; Group III (GIII; n=14): ADSCs injected on the 3rd day, and Group IV (GIV; n=7): ADSCs injected day 5(d5). Clinical evaluations were performed on days 0, 3, 5 and 7 and the histopathology on days 5 and 7. In the proposed methodology, the use of ADSCs increased vascularization, formation of granulation tissue, collagen deposition and increases the number of hair follicles in just seven days of evaluation. In addition, the time of application of the cells did not affect significant differences in the inflammatory and the proliferative phase of wound healing skin