Nimesulide-induced fatal acute liver failure in an elderly woman with metastatic biliary adenocarcinoma. A case report / Insuficiência hepática aguda fatal induzida por nimesulida em uma mulher idosa com adenocarcinoma biliar metastático. Um relato de caso

CONTEXT:Nimesulide is a selective inhibitor of the enzyme cyclooxygenase 2. Although considered to be a safe drug, cases of acute hepatitis and fulminant liver failure have been reported in Europe, the United States and South America, especially among elderly female patients. Until now, there had not been any reports in the literature relating to Brazilian subjects.CASE REPORT:An 81-year old female who had been using nimesulide therapy for six days presented hematemesis and epistaxis two days before hospitalization. Clinical examination showed an extensive coagulation disorder, diffuse hematomas, hypotension and tachypnea. Laboratory tests revealed abnormalities in coagulation tests; leukocytosis; reduced platelet, hemoglobin and red blood cell counts; and elevated direct bilirubin, serum aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase and renal function biomarkers. Hepatitis B and C tests were not reactive. Carcinoembryonic antigen (CEA), CA-19-9 and CA-125 levels were increased by, respectively, 1,000, 10,000 and 13 fold, whereas the alpha-fetoprotein level was normal, thus indicating a malignant tumor in the bile duct that did not originate from the liver. Thirty-six hours after hospitalization, the patient's condition worsened, leading to death. The necropsy findings included acute hepatitis with hepatocellular collapse, as well as metastasis of a carcinoma, probably from the bile duct.CONCLUSION:Despite the carcinoma presented by the patient, nimesulide use may have contributed towards the fatal acute liver failure. Until this issue has been clarified, caution is required in prescribing nimesulide for liver disease patients.

CONTEXTO:A nimesulida é um inibidor seletivo da enzima ciclo-oxigenase 2. Apesar de ela ser considerada fármaco seguro, casos de hepatite aguda e falência hepática fulminante foram descritos na Europa, Estados Unidos e América do Sul, principalmente em idosos do sexo feminino. Até o momento não há relatos na literatura em indivíduos brasileiros.RELATO DE CASO:Mulher de 81 anos, em uso terapêutico de nimesulida por seis dias, apresentou hematêmese e epistaxe dois dias antes da hospitalização. O exame clínico mostrou importante distúrbio de coagulação, hematomas difusos, hipotensão e taquipneia. Os exames laboratoriais mostravam alteração das provas de coagulação, leucocitose, redução do número de plaquetas, hemoglobina e hemácias, aumento de bilirrubina direta, elevação dos valores de aspartato aminotransferase (AST), gama glutamil transpeptidase (GGT), fosfatase alcalina e marcadores de função renal. Exames para hepatite B e C apresentaram-se não reagentes. Elevados níveis dos marcadores antígeno carcinoembriônico (CEA), CA-19-9 e CA-125 foram encontrados (1.000, 10.000 e 13 vezes, respectivamente), enquanto a alfa-fetoproteína estava normal, indicando um tumor maligno no ducto biliar, não oriundo do fígado. Trinta e seis horas após a hospitalização, a paciente evoluiu a óbito. Os achados necroscópicos incluíram hepatite aguda com colapso hepatocelular, bem como metástase de carcinoma, provavelmente do ducto biliar.CONCLUSÃO:Apesar do carcinoma apresentado pela paciente, o uso de nimesulida pode ter contribuído para o dano hepático. Até que esta questão seja esclarecida, a prescrição de nimesulida deve ser cuidadosa para pacientes com doenças hepáticas.

Protein Expression and Codon 72 Polymorphism of TP53 Gene in Triple Negative Breast Cancer

A subgroup of tumor that has received attention is triple-negative breast cancer (TNBC), which presents phenotype of negative estrogen receptor, negative progesterone receptor and has no overexpression of HER2. TP53 acts as a tumor suppressor limiting the proliferation of damaged cells. A polymorphic site (rs1042522) of TP53 encodes either an arginine or a proline amino acid, but its biological significance remains unclear. This study aimed to investigate this variant and its expression in search for a possible involvement in TNBC susceptibility and clinical outcome. Genetic polymorphism was evaluated in 50 patients and 115 controls by PCR based methodology and immunohistochemistry was done with monoclonal antibody. Case-control study showed no positive or negative association (OR= 0.95; CI95%= 0.48-1.89). Comparison of genotypes and clinical outcome showed no significant results. Despite most of patients presented p53 positive staining by immunohistochemistry, there was no significant association in relation to prognostic parameters. Results demonstrated a lack of association between codon 72 polymorphism, susceptibility and prognosis of TNBC. Immunohistochemistry analysis should be done more carefully, since most of the patients had the somatic mutation of p53, which could be an indicator of prognostic value in TNBC.

Correlação de fatores anatomopatológicos com a sobrevida de pacientes operados por adenocarcinoma colorretal / Correlation of pathological factors with survival of patients submitted to coloretal resections due to adenocarcinoma

OBJETIVO: Avaliar a influência de fatores anatomopatológicos como prognóstico na sobrevida de pacientes operados de adenocarcinoma colorretal. MÉTODOS: Estudo tipo coorte histórica aberta, baseado na análise de 119 pacientes operados de adenocarcinoma colorretal com intenção curativa no Hospital Universitário Júlio Muller, no período de 1984 a 2002. Os dados foram obtidos dos prontuários médicos e de exames anatomopatológicos revisados, sendo submetidos à análise estatística de sobrevida em cinco anos pelo método de Kaplan & Méier. O reto foi o segmento mais acometido em 44,5 por cento dos casos. O aspecto macroscópico tumoral predominante foi o ulcerado ou infiltrante (50,4 por cento), com tamanhos entre 2 e 17 cm, sendo que a maioria dos tumores (64,7 por cento) infiltrava até a camada serosa. O número médio de linfonodos analisados foi de 11,8(±7,3) por peça cirúrgica, indentificando-se nestes, 42,8 por cento de metástases. A maioria dos tumores (85,4 por cento) era bem ou moderadamente diferenciada. Foram observadas embolização angiolinfática e perineural em respectivamente 51,2 por cento e 23,5 por cento. RESULTADOS: Não houve significância estatística quanto a morfologia (p=0,87), tamanho do tumor (p=0,56) e grau de diferenciação celular (p=0,83). Os fatores que se correlacionaram com a sobrevida foram o sítio do tumor primário (p=0,04), a invasão angiolinfática intra-tumoral (p=0,02), invasão perineural (p<0,01), a infiltração das camadas (p=0,02), e o comprometimento linfonodal (p<0,01). CONCLUSÃO: A análise dos fatores anatomopatológicos mostrou correlação significativa da sobrevida com o sítio primário, a camada acometida, invasão perineural, invasão angiolinfática e comprometimento dos linfonodos.

BACKGROUND: The aim of this study was to evaluate the influence of the pathological aspects as prognostic for survival in patients who underwent resection for colorectal adenocarcinoma. METHOD: A historical cohort study was conducted based on an analysis of 119 patients with colorectal adenocarcinoma submitted to curative intention resection at the Department of Surgery of the Júlio Müller University Hospital from 1984 to 2002. Data were obtained from medical records. Specimen slides were reviewed and the findings were submitted to the survival analysis using the Kaplan-Meier method. The rectum was the location most frequent found (44,5 percent). The predominant macroscopic aspect was ulcerated or infiltrate type (50,4 percent), with lengths between 2 and 17 cm, and the majority of the tumors (64,7 percent) infiltrated until the serosa layer. The average number of lymph nodes examined in the surgical specimen was 11,8(±7,3) showing 42,8 percent of metastatic envolviment. Most of the tumors (85,4 percent) were categorized as either well or moderately differentiated. Angiolymphatic embolization and perineural invasion were observed in 51,2 percent and 23,5 percent respectively. RESULTS: There was no statistical significance of survival with morphology (p=0,87), length of the tumor (p=0,56) and degree of cellular differentiation (p=0,83). The factors that correlated with survival were location of the tumor (p=0,04), angiolymphatic embolization (p=0,02), perineural invasion (p <0,01), wall infiltration (p=0,02), and lymph node involvement (p <0.01). CONCLUSION: Survival of patients operated for colorectal adenocarcinoma showed significant correlation with site of the tumor, extension through gut layers, angiolymphatic embolization, perineural invasion, and lymphonodal involvement.