How pathological criteria can impact prognosis of tongue and floor of the mouth squamous cell carcinoma

Abstract Pathological parameters have been indicated as tumor prognostic factors in oral carcinoma. Objective: The objective of this study was to investigate the impact of pathological parameters on prognosis of patients affected only by tongue and/or floor of the mouth squamous cell carcinoma (SCC). Methodology: In total, 380 patients treated in the Brazilian National Cancer Institute (INCA) from 1999 to 2006 were included. These patients underwent radical resection followed by neck dissection. The clinical and pathological characteristics were recorded. The Kaplan-Meier method and Cox proportional hazards model were used in survival analysis. Overall survival (OS), cancer-specific survival (CSS) and disease-free interval (DFI) were estimated. Cox residuals were evaluated using the R software version 3.5.2. Worst OS, CSS and DFI were observed in patients with tumors in advanced pathological stages (p<0.001), with the presence of perineural invasion (p<0.001) and vascular invasion (p=0.005). Results: Advanced pathological stage and the presence of a poorly differentiated tumor were independent prognostic factors for OS and CSS. However, advanced pathological stage and perineural invasion were independent predictors of a shorter OS, DFI and CSS. Conclusion: Pathological stage and perineural invasion were the most significant pathological variables in survival analysis in tongue and/or floor of the mouth SCC.

Perfil dos Pacientes com Câncer de Esôfago Diagnosticados entre 2001 e 2010 no Brasil / Profile of Patients with Esophageal Cancer Diagnosed Between 2001 and 2010 in Brazil / Perfil de los Pacientes con Cáncer de Esófago Diagnosticados entre 2001 y 2010 en Brasil

Introdução: O câncer de esôfago é a terceira neoplasia mais comum do trato digestivo e apresenta prognóstico ruim quando diagnosticado em estádios avançados da doença. Objetivo: Descrever as características sociodemográficas, clínicas e de tratamento dos pacientes diagnosticados com câncer de esôfago no Brasil, no período de 2001 a 2010. Método: Estudo transversal de base secundária em pacientes com câncer de esôfago, cadastrados entre 2001 e 2010, nos Registros Hospitalares de Câncer. Foram analisadas as variáveis sociodemográficas, clínicas e de tratamento. Foi realizada análise descritiva utilizando média e desvio-padrão para as variáveis contínuas, e frequência absoluta e relativa para as categóricas. Resultados: Foram incluídos 24.204 pacientes, com média de idade de 60,8 anos (±11,5). A maioria da população era do sexo masculino (78,3%), de baixa escolaridade (75,2%), etilista (62,9%), tabagista (76,0%) e com estádio avançado ao diagnóstico (41,3% em estádio clínico III e 26,9%, IV), sendo o grupo topográfico de maior prevalência o esôfago superior e médio (76,4%). Não foram submetidos a nenhum tratamento oncológico 12,7% dos pacientes. Os tratamentos mais frequentes foram a combinação entre radioterapia e quimioterapia (25,6%) e o tratamento isolado com radioterapia (21,9%). Ao final do primeiro tratamento oncológico, 10,7% estavam sem evidência de doença, 8,4% com remissão parcial, 26,6% com doença estável e, os demais, com doença em progressão ou óbito (54,4%). Conclusão: No Brasil, os casos diagnosticados por câncer de esôfago são, em sua maioria, diagnosticados em estádios avançados da doença, o que representou maior agressividade terapêutica e pior resposta ao tratamento.

Introduction: Esophageal cancer is the third most common neoplasm of the digestive tract and presents poor prognosis when diagnosed in advanced stages of the disease. Objective: To describe the socio-demographic, clinical and treatment characteristics of patients diagnosed with esophageal cancer in Brazil, from 2001 to 2010. Method: A cross-sectional study of patients with esophageal cancer registered between 2001 and 2010 in Hospital-based registries. Socio-demographic, clinical and treatment variables were analyzed. Descriptive analysis was performed using mean and standard deviation for continuous variables, and absolute and relative frequency for categorical variables. Results: A total of 24,204 patients were included, with a mean age of 60.8 years (± 11.5). The majority of the population was male (78.3%), with a low level of schooling (75.2%), alcoholics (62.9%), smokers (76.0%), and had an advanced stage of diagnosis (41.3% in clinical stage III and 26.9% in stage IV), the topographic group being the most prevalent was in the esophagus upper and middle (76.4%). 12.7% of the patients were not submitted to any cancer treatment. The most frequent treatments were the combination of radiotherapy and chemotherapy (25.6%), and treatment alone with radiotherapy (21.9%). At the end of the first cancer treatment, 10.7% had no evidence of disease, 8.4% had partial remission, 26.6% had a stable disease, and the remaining patients had progression or death (54.4%). Conclusion: In Brazil, the cases diagnosed for esophageal cancer are mostly diagnosed in advanced stages of the disease, which represents greater therapeutic aggressiveness and worse response to treatment.

Introducción: El cáncer de esófago es la tercera neoplasia más común del tracto digestivo y presenta un pronóstico malo cuando se diagnostica en estadios avanzados de la enfermedad. Objetivo: Describir las características sociodemográficas, clínicas y de tratamiento de los pacientes diagnosticados con cáncer de esófago en Brasil, en el período de 2001 a 2010. Método:Estudio transversal de base secundaria en pacientes con cáncer de esófago, registrados entre 2001 y 2010, en los Registros Hospitalarios de Cáncer. Se analizaron las variables sociodemográficas, clínicas y de tratamiento. Se realizó un análisis descriptivo utilizando media y desviación estándar, para las variables continuas, y frecuencia absoluta y relativa para las categóricas. Resultados: Se incluyeron 24.204 pacientes, con una media de edad de 60,8 años (±11,5). La mayoría de la población era del sexo masculino (78,3%), de baja escolaridade (75,2%), etilista (62,9%), tabaquista (76,0%) y con estadio avanzado al diagnóstico (41,3% en estadio clínico III y 26,9% en estadio IV), siendo el grupo topográfico de mayor prevalencia el esófago superior y medio (76,4%). No fueron sometidos a ningún tratamiento oncológico, el 12,7% de los pacientes. Los tratamientos más frecuentes fueron la combinación entre radioterapia y quimioterapia (25,6%), y el tratamiento aislado con radioterapia (21,9%). Al final del primer tratamiento oncológico, el 10,7% estaba sin evidencia de enfermedad, el 8,4% con remisión parcial, el 26,6% con enfermedad estable y los demás, con enfermedad en progresión o muerte (54,4%). Conclusión: En Brasil, los casos diagnosticados por cáncer de esófago son en su mayoría, diagnosticados en estadios avanzados de la enfermedad, lo que representó mayor agresividad terapéutica y peor respuesta al tratamiento.

Evaluation of the heme oxygenase-1 expression in esophagitis and esophageal cancer induced by different reflux experimental models and diethylnitrosamine / Avaliação da expressão da Heme Oxigenase-1 em esofagite e câncer de esôfago induzidos por diferentes modelos experimentais de refluxo e diethilnitrosamina

PURPOSE: To study the expression of heme-oxygenase-1 (HO-1), an enzyme induced by oxidative stress, in specimens obtained from an experimental model in rats that evaluated the role of gastric and duodenal reflux in esophageal carcinogenesis. METHODS: Esophageal specimens embedded in paraffin obtained from different experimental groups of rats were used for immunohistochemistry analysis of HO-1 expression. The rats had been divided into the following groups and were killed after 22 weeks: (1) cardioplasty to induce acid reflux; (2) esophagoduodenal anastomosis to induce duodenal reflux; (3) no treatment; (4) cardioplasty + diethylnitrosamine (DEN); (5) esophagoduodenal anastomosis + DEN; and (6) DEN. The study sample comprised 3 specimens from each group with the most severe histopathological lesions found on each study branch. RESULTS: The expression of HO-1 was seen only in rat specimens submitted to esophagoduodenal anastomosis (Groups 2 and 5), and the analysis of mean fluorescence intensity revealed a significant increase of HO-1 expression (4.8 and 4.6 fold, respectively) when compared with the control group (Group 3) (p<0.05). The main target for HO-1 induction was the inflammatory cells inside the tumor or in subepithelial areas. Rats exposed to gastric reflux had no HO-1 expression. CONCLUSION: Reflux esophagitis induced by reflux of duodenal contents, which provoked considerable oxidative stress, may play an important role in esophageal carcinogenesis. Acid reflux did not induce oxidative stress in this experimental model.

OBJETIVO: Estudar a expressão da HO-1 (enzima induzida pelo estresse) em diferentes peças esofágicas obtidas de um estudo experimental em ratos que avaliou o papel do refluxo gastroesofágico e duodeno esofágico na carcinogênese experimental. MÉTODOS: Blocos de parafina contendo peças de esôfago provenientes de um estudo experimental com ratos foram utilizados para verificar a expressão imunohistoquímica da HO-1. Os ratos haviam sido divididos nos seguintes grupos: (1) Cardioplastia com o objetivo de promover refluxo ácido, (2) Anastomose esofagoduodenal para indução de refluxo misto (ácido e biliar), (3) sem tratamento (controles), (4) cardioplastia + dietil-nitrosamina (DEN), (5) Anastomose esofagoduodenal + DEN, (6) DEN. Amostras contendo três peças de cada grupo com as lesões histopatológicas mais graves encontradas em cada braço do estudo foram escolhidas para avaliação da expressão imunoistoquímica da HO-1. RESULTADOS: A expressão da HO-1 foi observada somente nas peças de esôfago de ratos submetidos à anastomose esofagoduodenal (Grupos 2 e 5) e analise da intensidade média da fluorescência demonstrou uma diferença significativa na expressão da HO-1 nesses grupos quando comparada com o grupo controle (4,8 e 4,6 vezes respectivamente) (p<0,05). As células inflamatórias localizadas dentro dos tumores e nas regiões adjacentes ao epitélio foram as que mais intensamente expressaram a HO-1. Ratos expostos ao refluxo ácido (gástrico) apresentaram pouca ou nenhuma atividade da HO-1. CONCLUSÃO: Esofagite de refluxo induzida pelo refluxo com conteúdo duodenal provocou considerável estresse oxidativo, que parece exercer um papel importante na carcinogênese esofágica. O refluxo puramente ácido não foi capaz de induzir estresse oxidativo nesse modelo experimental

Standardization of conditions for the metabolic activation of N-nitrosodiethylamine in mutagenicity tests

Like all nitrosamines, N-nitrosodiethylamine (NDEA) requires metabolic activation in order to exert its carcinogenic effects. This activation involves cytochrome P450s (CYP), which generates unstable metabolites that react with the DNA of cells in the immediate vicinity of metabolite formation. Although NDEA is carcinogenic, it has been considered a weak mutagen in classic genotoxicity assays. We used optimized Salmonella/mammalian microsome genotoxicity assays to assess the mutagenicity and toxicity of low concentrations of NDEA. Using a fixed concentration of NDEA (36.5 mg/ml), we varied the length of preincubation in the presence of different concentrations of an S9 metabolic activation mixture. Salmonella typhimurium strains TA97 and TA102 were resistant to NDEA-induced mutagenesis, even after a preincubation of up to 120 min and the use of different concentrations of the S9 mix. Strain TA98 was susceptible to mutagenesis by NDEA in the absence of the S9 mix and after preincubation with NDEA for 90 min. When bacteria of this strain were preincubated with NDEA for 60 min, mutagenesis was detected at an S9 mix concentration >9.55 mg/ml. NDEA also induced mutagenesis in strain TA100 after preincubation for 90 or 120 min, and this effect was dependent on the S9 concentration. E. coli strain BH990 also showed a concentration-dependent response, with only 60% of the cells surviving after a 120-min preincubation with NDEA in the presence of 19.1 mg S9 mix/ml.