Risk factors for oral mucositis in patients with solid tumors under treatment with cetuximab: a retrospective cross-sectional study.

BACKGROUND: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment. MATERIAL AND METHODS: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. We collected information from 2 years of evaluations. Patient medical records were reviewed to obtain data on chemotherapy cycle and dose, sex, age, primary tumor, TNM stage, and head and neck radiotherapy (HNR) history. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05). RESULTS: Among 1831 patients, OM was showed in 750 in any grade (41%), during cetuximab treatment. Most patients were female (n=944, 51.6%), <70years-old (n=1149, 62.8%), had larynx cancer (n=789, 43.1%) in T4 (n=579, 47.7%), N0 (n=509, 52.6%) stages. Primary tumor surgery was performed in 1476 (80.6%) patients, radiotherapy in 606 (33.1%) patients and cetuximab protocols most used involved up to four cycles (n=1072, 58.5%) of <400mg (n=996, 54.4%) cetuximab doses. Female (OR [odds ratio] = 2.17, CI95% = 1.26-3.75), >70 years-old patients (OR = 16.02, CI95% = 11.99-21.41), with HHNR (OR = 1.84, 1.41-2.40), treated with >4 cycles (OR = 1.52, CI95% = 1.16-2.01) and high doses of cetuximab (OR = 3.80, CI95% = 2.52-5.71) are the greatest risk factors for OM. CONCLUSIONS: Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution.

Prevalence of autosomal dominant polycystic kidney disease in Persian and Persian-related cats in Brazil / Prevalência da doença renal policística autossômica dominante em gatos Persas e raças relacionadas no Brasil

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease in cats. However, scarce data on its prevalence are available in Brazil. Persian cats and Persian-related breeds were assessed by molecular genotyping for a C to A transversion in exon 29 of PKD1 gene to determine ADPKD prevalence in a Brazilian population. Genomic DNA extracted from peripheral whole blood or oral swabs samples was used to amplify exon 29 of PKD1 gene employing a PCR-RFLP methodology. From a total of 616 animals, 27/537 Persian and 1/17 Himalayan cats showed the single-nucleotide variant (C to A) at position 3284 in exon 29 of feline PKD1. This pathogenic variation has been identified only in heterozygous state. The prevalence of ADPKD in Persian cats and Persian-related breeds was 5.03% and 1.6%, respectively. There was no significant association between feline breed, gender or age with ADPKD prevalence. Of note, the observed ADPKD prevalence in Persian cats and Persian-related breeds in Brazil was lower than the ones reported in other parts of the world. This finding may be related to genetic counseling and consequent selection of ADPKD-free cats for reproduction.

A doença renal policística autossômica dominante (DRPAD) é a doença genética mais comum em gatos. No entanto, poucos dados sobre sua prevalência estão disponíveis no Brasil. Gatos Persas e de raças relacionadas foram avaliados por genotipagem molecular para a transversão C→A no exon 29 do gene PKD1 felino para determinar a prevalência de DRPAD. DNA genômico extraído de sangue total periférico ou amostras de swabs orais foram utilizados para amplificar o exon 29 do gene PKD1 pela técnica de PCR-RFLP. De um total de 616 gatos, 27/537 Persas e 1/17 Himalaia mostraram a variante de nucleotídeo único (C→A) na posição 3284 no exon 29 do gene PKD1. Esta variante patogênica foi identificada apenas em heterozigose. A prevalência de DRPAD em gatos Persas e raças relacionadas foram de 5,03% e 1,6%, respectivamente. Não houve associações significativas entre raça, gênero ou idade dos felinos e incidência de DRPAD. A prevalência de DRPAD em gatos Persas e raças relacionadas no Brasil foi menor do que em outras partes do mundo, o que pode estar relacionado ao aconselhamento genético e consequente seleção de gatos sem ADPKD para reprodução.

Cutaneous schistosomiasis and leishmaniasis coinfection: a case report.

BACKGROUND: The polymorphic clinical presentations of schistosomiasis and leishmaniasis allow their inclusion in the differential diagnoses of several conditions. Although an overlap in distribution of these diseases has been reported in endemic areas, coinfection with cutaneous schistosomiasis and cutaneous leishmaniasis in the same patient is rare. OBJECTIVES: We report an unusual case of concomitant cutaneous schistosomiasis and cutaneous leishmaniasis. Actions for the management and diagnosis were proposed. METHODS: A patient presented with cutaneous lesions on the abdomen and left elbow. The presence of degenerated ova of Schistosoma mansoni in the skin biopsy led to perform a complementary investigation with immunohistochemical techniques, rectal biopsy and abdominal ultrasonography. After the left elbow lesions had failed to improve after several weeks of standard treatment, a new biopsy was performed and led to diagnosis of another infection. RESULTS: The patient lived in an endemic area for two infectious diseases (schistosomiasis and leishmaniasis). Biopsies revealed chronic granulomatous dermatitis. Degenerated S. mansoni eggs were found in the abdominal lesion and in a rectal biopsy specimen. Ultrasonography revealed hepatic involvement. Despite combination treatment with oxamniquine and praziquantel, a cutaneous lesion persisted on the left elbow; a new biopsy revealed amastigote forms of Leishmania. The patient was successfully treated with intramuscular and intralesional meglumine antimoniate. CONCLUSIONS: The presence of a similar granulomatous infiltrate in lesions caused by the two different infectious agents led to a delay in the diagnosis of cutaneous leishmaniasis. This report serves as a warning of the unusual possibility of cutaneous schistosomiasis and leishmaniasis coinfection in an endemic area.

Parotid Salivary Gland Basal Cell Adenocarcinoma in a Big-eared Opossum (Didelphis aurita).

The opossum (family Didelphidae) is a marsupial endemic to the Americas. Apart from the South American short-tailed opossum (Monodelphis domestica) and the Virginia opossum (Didelphis virginiana), there is considerable lack of knowledge about the health and diseases of most opossum species. Among these, the big-eared opossum (Didelphis aurita) is found in Argentina, Brazil and Paraguay. Natural and experimental studies have shown this species to be susceptible to infectious agents with zoonotic potential and the animals may play a role in transmission of such agents. However, neoplasia appears to be uncommon in this species. We describe the gross, microscopical and immunohistochemical features of a parotid salivary gland basal cell adenocarcinoma in a free-living big-eared opossum. This case represents the first report of salivary gland neoplasia in opossums.

Multicentric cutaneous keratoacanthomas in a free-living marmoset (Callithrix sp.).

Cutaneous neoplasia is common in non-human primates. We describe the gross and microscopic features of multicentric cutaneous keratoacanthomas in a free-living marmoset (Callithrix sp.). Immunohistochemistry for human papillomavirus and herpes simplex virus type I and simplex virus type II was negative. Keratoacanthomas should be included in the differential diagnosis for cutaneous masses in non-human primates.

[Reason for consultation: Weight loss]. / Motivo de consulta: pérdida de peso.

BACKGROUND AND OBJECTIVE: Unintentional weight loss is frequent reason to visit a doctor and it has multiple diagnostic possibilities. The objective of this study is to examine the background of the patients who seek consultation for weight loss and to establish the relationship between weight loss and neoplasia. METHOD: An analysis was performed on the demographic data, quantified weight loss, accompanying symptomatology, and diagnosis of patients who sought medical advice for unintentional weight loss during the year 2015. RESULTS: A total of 226 patients were included, of whom 44.2% of them had an intentional weight loss ≥ 5% in 6 months. The most frequent diagnosis in this group was a neoplasia, whereas in the rest of patients the most common diagnosis was a gastrointestinal disease. In light of this study we can conclude that there is a relationship between unintentional weight loss≥5% and the presence of neoplasia. CONCLUSION: An unintentional weight loss greater than 5% in the previous 6 months is associated with the presence of neoplastic diseases, and therefore requires further diagnostic study.

Spontaneous pulmonary adenosquamous carcinoma in a free-living black capuchin monkey (Sapajus nigritus).

Pulmonary neoplasia is rare among wild New World primates. We report the gross, microscopical, and immunohistochemical features of a primary multicentric pulmonary adenosquamous carcinoma in a free-living black capuchin monkey (Sapajus nigritus). Herein, the spectrum of pulmonary neoplasms in non-human primates is widened and briefly reviewed.

Hepatocellular carcinoma in a free-living marmoset (Callithrix sp.) with concomitant biliary trematodiasis.

Hepatocellular carcinoma (HCC) is rare in New World primates. We report the gross, microscopical, and immunocytochemical features of a spontaneous HCC in a free-living marmoset (Callithrix sp.). Hepatitis B and C virus and aflatoxin immunohistochemistry were negative; however, concomitant intra- and extrahepatic biliary trematodiasis could have played a role.

Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer / Modelo de enxerto tumoral ortotópico em camundongos para avaliar os efeitos do calcitriol em câncer de mama

Abstract Calcitriol antiproliferative effects were observed in xenografts of breast cancer cell lines, however they were not yet investigated in tumorgrafts, consisting of freshly collected breast cancer samples xenografted into animals. Objectives To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects. Methods Breast cancer samples collected from 12 patients were orthotopically implanted into nude mice. Animals were treated with weekly intratumoral injections of calcitriol 3 μg/Kg, which was previously shown to induce peak serum calcitriol levels in the predicted therapeutic range. Results Success engraftment rate was 25%. Tumorgrafts were established from aggressive (HER2 positive or histological grade 3) highly proliferative samples and original tumor characteristics were preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that the genomic vitamin D pathway is active in tumorgrafts. However, no differences in the expression of proliferation and apoptosis markers (BrdU incorporation, Ki67, CDKN1A, CDKN1B, BCL2 expression) were observed in these highly proliferative tumor samples. Conclusions Tumorgrafts seem a promising model to explore other calcitriol doses and regimens, considering the heterogeneity of the disease and microenvironment interactions.

Resumo Os efeitos antiproliferativos de calcitriol foram observados em xenotransplantes de linhagens celulares de câncer de mama, entretanto, não foram ainda investigados em enxertos tumorais, consistindo de implantes em animais de amostras de câncer de mama recém-coletadas. Objetivos Estabelecer modelo de enxerto tumoral, a partir de amostra de câncer de mama recém-coletada e diretamente implantada em camundongos nude, para estudar o efeito do calcitriol. Métodos Amostras de câncer de mama de 12 pacientes foram implantadas ortotopicamente em camundongos nude. Os animais foram tratados com injeção intratumoral semanal de calcitriol 3 μg/Kg, a qual foi previamente associada com indução de pico sérico de calcitriol dentro do intervalo de nível terapêutico. Resultados A taxa de sucesso de pega do enxerto foi de 25%. Os enxertos tumorais foram estabelecidos de tumores agressivos com alta taxa de proliferação (HER2 positivo ou grau histológico 3) e as características do tumor original foram preservadas. O calcitriol induziu fortemente a expressão do gene alvo, CYP24A1, indicando que a via genômica da vitamina D está ativa nos enxertos tumorais, entretanto, não se observou diferenças na expressão de marcadores de proliferação e apoptose (incorporação de BrdU, expressão de Ki67, CDKN1A, CDKN1B e BCL2) nestas amostras altamente proliferativas. Conclusões Os enxertos tumorais parecem ser um modelo promissor para explorar outros esquemas e doses de calcitriol, considerando a heterogeneidade da doença e interações com o microambiente.

Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer.

OBJECTIVES: Calcitriol antiproliferative effects were observed in xenografts of breast cancer cell lines, however they were not yet investigated in tumorgrafts, consisting of freshly collected breast cancer samples xenografted into animals. To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects. METHODS: Breast cancer samples collected from 12 patients were orthotopically implanted into nude mice. Animals were treated with weekly intratumoral injections of calcitriol 3 µg/Kg, which was previously shown to induce peak serum calcitriol levels in the predicted therapeutic range. RESULTS: Success engraftment rate was 25%. Tumorgrafts were established from aggressive (HER2 positive or histological grade 3) highly proliferative samples and original tumor characteristics were preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that the genomic vitamin D pathway is active in tumorgrafts. However, no differences in the expression of proliferation and apoptosis markers (BrdU incorporation, Ki67, CDKN1A, CDKN1B, BCL2 expression) were observed in these highly proliferative tumor samples. CONCLUSIONS: Tumorgrafts seem a promising model to explore other calcitriol doses and regimens, considering the heterogeneity of the disease and microenvironment interactions.

Prevalence of autosomal dominant polycystic kidney disease in Persian and Persian-related cats in Brazil

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease in cats. However, scarce data on its prevalence are available in Brazil. Persian cats and Persian-related breeds were assessed by molecular genotyping for a C to A transversion in exon 29 of PKD1 gene to determine ADPKD prevalence in a Brazilian population. Genomic DNA extracted from peripheral whole blood or oral swabs samples was used to amplify exon 29 of PKD1 gene employing a PCR-RFLP methodology. From a total of 616 animals, 27/537 Persian and 1/17 Himalayan cats showed the single-nucleotide variant (C to A) at position 3284 in exon 29 of feline PKD1. This pathogenic variation has been identified only in heterozygous state. The prevalence of ADPKD in Persian cats and Persian-related breeds was 5.03% and 1.6%, respectively. There was no significant association between feline breed, gender or age with ADPKD prevalence. Of note, the observed ADPKD prevalence in Persian cats and Persian-related breeds in Brazil was lower than the ones reported in other parts of the world. This finding may be related to genetic counseling and consequent selection of ADPKD-free cats for reproduction.

Resumo A doença renal policística autossômica dominante (DRPAD) é a doença genética mais comum em gatos. No entanto, poucos dados sobre sua prevalência estão disponíveis no Brasil. Gatos Persas e de raças relacionadas foram avaliados por genotipagem molecular para a transversão CA no exon 29 do gene PKD1 felino para determinar a prevalência de DRPAD. DNA genômico extraído de sangue total periférico ou amostras de swabs orais foram utilizados para amplificar o exon 29 do gene PKD1 pela técnica de PCR-RFLP. De um total de 616 gatos, 27/537 Persas e 1/17 Himalaia mostraram a variante de nucleotídeo único (CA) na posição 3284 no exon 29 do gene PKD1. Esta variante patogênica foi identificada apenas em heterozigose. A prevalência de DRPAD em gatos Persas e raças relacionadas foram de 5,03% e 1,6%, respectivamente. Não houve associações significativas entre raça, gênero ou idade dos felinos e incidência de DRPAD. A prevalência de DRPAD em gatos Persas e raças relacionadas no Brasil foi menor do que em outras partes do mundo, o que pode estar relacionado ao aconselhamento genético e consequente seleção de gatos sem ADPKD para reprodução.

Liquid-based cytology and cell block immunocytochemistry in veterinary medicine: comparison with standard cytology for the evaluation of canine lymphoid samples.

Liquid-based Cytology (LBC) consists of immediate wet cell fixation with automated slide preparation. We applied LBC, cell block (CB) and immunocytochemistry to diagnose canine lymphoma and compare results with conventional cytology. Samples from enlarged lymph nodes of 18 dogs were collected and fixed in preservative solution for automated slide preparation (LBC), CB inclusion and immunophenotyping. Two CB techniques were tested: fixed sediment method (FSM) and agar method (AM). Anti-CD79a, anti-Pax5, anti-CD3 and anti-Ki67 were used in immunocytochemistry. LBC smears showed better nuclear and nucleolar definition, without cell superposition, but presented smaller cell size and worse cytoplasmic definition. FSM showed consistent cellular groups and were employed for immunocytochemistry, while AM CBs presented sparse groups of lymphocytes, with compromised analysis. Anti-Pax-5 allowed B-cell identification, both in reactive and neoplastic lymph nodes. Our preliminary report suggests that LBC and FSM together may be promising tools to improve lymphoma diagnosis through fine-needle aspiration.

Renal flare prediction and prognosis in lupus nephritis Hispanic patients.

We performed a retrospective cohort analysis focusing on lupus nephritis renal flare incidence and outcome predictors. One hundred and eighteen patients with biopsy-proven lupus nephritis were segregated by induction/maintenance regimes. The primary outcome was the proportion of patients experiencing renal flare. Secondary assessment included doubling of serum creatinine and development of end-stage renal disease. After a median follow-up of 31 months (interquartile range 21-46) from the date of response to induction therapy, 47 patients (39.8%) developed a renal flare. Azathioprine-maintained patients had a higher risk of renal flare compared with mycophenolate mofetil-maintained patients (hazard ratio 2.53, 95% confidence interval 1.39-4.59, p < 0.01). Age (hazard ratio 0.96, 0.92-0.99, p = 0.03), serum creatinine at presentation (hazard ratio 1.76, 1.13-2.76, p = 0.01), complete remission after induction therapy (hazard ratio 0.28, 0.14-0.56, p < 0.001) and azathioprine maintenance therapy (hazard ratio 4.78, 2.16-10.6, p < 0.001) were associated with renal flare on multivariate analysis. Ten patients progressed to end-stage renal disease (8.5%) by a median 32.5 months. Age (hazard ratio 0.88, 0.77-0.99, p = 0.05), complete remission after induction therapy (hazard ratio 0.08, 0.01-0.94, p = 0.04) and severe nephritic flare (hazard ratio 13.6, 1.72-107.7, p = 0.01) were associated with end-stage renal disease development. Azathioprine maintenance therapy is associated with a higher incidence of relapse in the Mexican-mestizo population. Younger age and nephritic flares predict development of end-stage renal disease.

[Microwave ablation of a sarcoma lung metastasis in a patient with a pacemaker]. / Ablación mediante microondas de metástasis pulmonar de sarcoma en paciente portador de marcapasos.

We present the case of a patient with a pacemaker and a sarcoma lung metastasis treated with microwave ablation. Although the treatment of tumours with microwave ablation is a successful and minimally invasive approach, there are concerns about the safety of this procedure for patients with implanted cardiac devices, such as a pacemaker. After careful planning between radiology and cardiology, microwave ablation was indicated in the patient since it is safer and shorter than the radiofrequency technique. The lesion was treated without complications. It is important to communicate the procedures performed, as well as any complications in order to formulate guidelines for the use of microwave ablation in patients with pacemakers.

Choroid plexus papilloma in a Rottweiler: computed tomographic, gross morfological and histological features / Papiloma do plexo coroide em um cão da raça Rottweiler: aspectos tomográficos, macroscópicos e histológicos

Among the tumors affecting the choroid plexus in dogs, the papilloma ranks second place in incidence after cell carcinoma tumors. Presumptive diagnosis can be made through imaging methods, such as computed tomography and magnetic resonance images. Definitive diagnosis of plexus choroid tumor is based on histopathological findings. This report presented the tomographic features of the brain in a 6-year-old intact female Rottweiler with choroid plexus papilloma. The computed tomography showed right lateral ventricle enlargement, midline deviation and an enhanced mass into the postcontrast phase. At necropsy, a mass on the floor of the right lateral ventricle was observed, associated with important ventricle dilatation. The histopathological analysis demonstrated the presence of neoplastic cell forms with papillary projections. The computed tomography proved to be an effective tool in the presumptive diagnosis of this kind of cerebral disorder.

Dentre os tumores que afetam o plexo coroide em cães, o papiloma figura como o segundo tipo de maior incidência, antecedido apenas pelo carcinoma. O diagnóstico presuntivo pode ser elaborado por meio de métodos de imagem, como a tomografia computadorizada e a ressonância magnética. O diagnóstico definitivo de tumor do plexo coroide é estabelecido com base nos achados histopatológicos. Relatamos os aspectos tomográficos do crânio em uma fêmea de 6 anos, inteira, da raça Rottweiler, com papiloma do plexo coroide. A tomografia computadorizada revelou dilatação do ventrículo lateral direito, desvio da linha média e a presença de uma massa, que sofreu realce na fase pós-contraste. À necropsia, foi observada uma massa sobre o assoalho do ventrículo lateral direito, associada à importante dilatação ventricular. A análise histopatológica demonstrou a presença de células poligonais neoplásicas, arranjadas em papilas longas. A tomografia computadorizada apresentou-se como uma ferramenta eficaz no diagnóstico presuntivo desse tipo de alteração cerebral.