Diet and esophageal disease.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on macronutrients, dietary patterns, and risk of adenocarcinoma in Barrett's esophagus; micronutrients, trace elements, and risk of Barrett's esophagus and esophageal adenocarcinoma; the role of mate consumption in the development of squamous cell carcinoma; the relationship between energy excess and development of esophageal adenocarcinoma; and the nutritional management of the esophageal cancer patient.

Stepwise expression of CDKN2A and RB1 proteins in esophageal mucosa from patients at high risk for squamous cell carcinoma.

Squamous cell carcinoma of the esophagus is a lethal cancer and carries a poor prognosis because of late diagnosis. Identification of molecular markers may aid early diagnosis. We assessed the expression of CDKN2A/RB1 in the esophageal mucosa and its association with the histology. Esophageal biopsies were collected from 38 patients with no esophageal lesion (group 1), from iodine-negative areas of 108 alcoholics/smokers (group 2), and from tumor and nontumor areas in 41 patients with squamous cell carcinoma (group 3). The histologic diagnosis was compared with immunoexpression of CDKN2A/RB1. In group 1, histology showed normal mucosa/mild esophagitis and no expression of CDKN2A/RB1. In groups 2 and 3, the diagnosis was: normal mucosa (38.4%), esophagitis (44.4%), dysplasia and carcinoma in situ (2.8%), and carcinoma (14.3%). The immunoexpression of CDKN2A/RB1 increased in a stepwise manner from the normal mucosa, to esophagitis, dysplasia/carcinoma in situ, and carcinoma (P<0.01). CDKN2A/RB1 was not expressed in the esophageal mucosa of patients without risk factors. p16/pRb expression increased in a stepwise manner, according to the severity of histologic lesions, in biopsies from patients exposed to risk factors or with carcinoma. Esophageal mucosa exposed to risk factors with the expression of those proteins may be at risk for malignant transformation.

Significant variation in the concentration of carcinogenic polycyclic aromatic hydrocarbons in yerba maté samples by brand, batch, and processing method.

Drinking maté, common in southern South America, may increase the risk of esophageal squamous cell carcinoma (ESCC). In 2006, we found high but variable polycyclic aromatic hydrocarbon (PAH) content in commercial yerba maté samples from eight Brazilian brands. The PAH content of new samples from the same brands, purchased in 2008, and four brands from a single manufacturer processed in different ways, obtained in 2010, were quantified to determine whether PAH concentration was still high, whether PAH content variation was brand specific, and whether processing method affects PAH content of commercial yerba maté. Concentrations of individual PAHs were quantified using gas chromatography/mass spectrometry with deuterated PAHs as internal standards. Median total PAH concentration was 1500 ng/g (range: 625-3710 ng/g) and 1090 ng/g (621-1990 ng/g) in 2008 and 2010 samples, respectively. Comparing 2006 and 2008 samples, some brands had high PAH concentrations in both years, while PAH concentration changed considerably in others. Benzo[a]pyrene concentrations ranged from 11.9 to 99.3 ng/g and 5.11 to 21.0 ng/g in 2008 and 2010 samples, respectively. The 2010 sample processed without touching smoke had the lowest benzo[a]pyrene content. These results support previous findings of very high total and carcinogenic PAH concentrations in yerba maté, perhaps contributing to the high incidence of ESCC in southern South America. The large PAH content variation by brand, batch, and processing method suggests it may be possible to reduce the content of carcinogenic PAHs in commercial yerba maté, making it a healthier beverage.

Gastric adenocarcinoma trends in the central region of Rio Grande do Sul (Southern Brazil): what has changed in 25 years?

CONTEXT: Gastric cancer is the fourth most common malignancy in the world. Its incidence varies greatly by geographic region. The highest rate is in Eastern Asia, mainly in Japan and China. In Brazil, gastric cancer is the third most common cancer in males and the fifth most common cancer in females. Rio Grande do Sul state, in Southern Brazil, has similar figures. The main histological type of gastric cancer is adenocarcinoma. OBJECTIVE: To assess the trends of this cancer over 25 years in a reference center in central Rio Grande do Sul. METHODS: We reviewed the records of upper gastrointestinal endoscopies performed at the University Hospital of Santa Maria, RS, between 1986 and 2010. We evaluated the incidence, age and gender distribution, anatomical subsite and histological subtype of gastric cancer throughout this 25-year period. RESULTS: We identified histologically confirmed primary gastric adenocarcinoma in 335 (1.6%) of the 20,521 patients who underwent upper gastrointestinal endoscopy during the study period. The mean age of patients was 62.4 (± 13.0) years, and 67.8% were male (a male: female ratio of 2.0:1). Cardia cancer accounted for 14.3% of the cases, and non-cardia cancer accounted for 85.7%. According to Lauren's classification, 48.1% were intestinal subtype and 40.9% were diffuse subtype. There were no differences in mean age or gender distribution by anatomical location or histological subtype. There was also no difference in the proportions of histological subtypes by anatomical location. Over the 25-year period, there was no change in the anatomical distribution of tumors, but there was a significant decrease in the intestinal subtype and a steady increase in the diffuse subtype (P = 0.02). The subset of 39 patients (11.6%) who presented at < 45 years of age was more likely to be female and to have tumors of the diffuse subtype than was the total series of patients. CONCLUSIONS: Over this 25-year period, there were no significant trends in age, gender distribution, or the proportions of cardia and non-cardia gastric adenocarcinomas in this series of patients from Southern Brazil. There was a significant decrease in the intestinal subtype and a steady increase in the diffuse subtype of this malignancy. In patients under 45 years old, gastric cancer was more frequent in women, and the diffuse subtype predominated.

Gastric adenocarcinoma trends in the central region of Rio Grande do Sul (Southern Brazil): what has changed in 25 years? / Tendência temporal do adenocarcinoma do estômago na região central do Rio Grande do Sul: o que mudou em 25 anos?

CONTEXT: Gastric cancer is the fourth most common malignancy in the world. Its incidence varies greatly by geographic region. The highest rate is in Eastern Asia, mainly in Japan and China. In Brazil, gastric cancer is the third most common cancer in males and the fifth most common cancer in females. Rio Grande do Sul state, in Southern Brazil, has similar figures. The main histological type of gastric cancer is adenocarcinoma. OBJECTIVE: To assess the trends of this cancer over 25 years in a reference center in central Rio Grande do Sul. METHODS: We reviewed the records of upper gastrointestinal endoscopies performed at the University Hospital of Santa Maria, RS, between 1986 and 2010. We evaluated the incidence, age and gender distribution, anatomical subsite and histological subtype of gastric cancer throughout this 25-year period. RESULTS: We identified histologically confirmed primary gastric adenocarcinoma in 335 (1.6%) of the 20,521 patients who underwent upper gastrointestinal endoscopy during the study period. The mean age of patients was 62.4 (± 13.0) years, and 67.8% were male (a male: female ratio of 2.0:1). Cardia cancer accounted for 14.3% of the cases, and non-cardia cancer accounted for 85.7%. According to Lauren's classification, 48.1% were intestinal subtype and 40.9% were diffuse subtype. There were no differences in mean age or gender distribution by anatomical location or histological subtype. There was also no difference in the proportions of histological subtypes by anatomical location. Over the 25-year period, there was no change in the anatomical distribution of tumors, but there was a significant decrease in the intestinal subtype and a steady increase in the diffuse subtype (P = 0.02). The subset of 39 patients (11.6%) who presented at < 45 years of age was more likely to be female and to have tumors of the diffuse subtype than was the total series of patients. CONCLUSIONS: Over this 25-year period, there were no significant trends in age, gender distribution, or the proportions of cardia and non-cardia gastric adenocarcinomas in this series of patients from Southern Brazil. There was a significant decrease in the intestinal subtype and a steady increase in the diffuse subtype of this malignancy. In patients under 45 years old, gastric cancer was more frequent in women, and the diffuse subtype predominated.

CONTEXTO: O câncer gástrico é a quarta neoplasia mais frequente no mundo e sua incidência varia de acordo com a região estudada. É mais frequente nos países asiáticos, principalmente Japão e China. No Brasil, é o terceiro e quinto câncer mais comum em homens e mulheres, respectivamente. Estas taxas são similares no Rio Grande do Sul e o principal tipo histológico é o adenocarcinoma. OBJETIVO: Investigar o comportamento deste câncer no período de 25 anos em um centro de referência na região central do Rio Grande do Sul. MÉTODOS: Foram revisados os laudos das endoscopias digestivas altas realizadas no Hospital Universitário de Santa Maria, RS, entre 1986 e 2010. Avaliaram-se a incidência, distribuição por faixa etária, sexo, subsítio anatômico e subtipo histológico do câncer gástrico ao longo deste período. RESULTADOS: Entre 20.521 pacientes submetidos a endoscopia digestiva alta, no período estudado, foram identificados 335 (1,6%) pacientes com adenocarcinoma gástrico. A idade média dos pacientes foi 62,4 (± 13,0) anos e 67,8% pertenciam ao sexo masculino (razão homem:mulher de 2:1). Câncer da cárdia ocorreu em 14,3% e não-cárdico em 85,7% dos casos. Na classificação de Lauren, 48,1% foram classificados como subtipo intestinal em 48,1% e difuso em 40,9%. Não houve diferenças na distribuição por idade ou sexo em relação à localização anatômica ou subtipo histológico, assim como na proporção dos subtipos histológicos em relação à localização anatômica. No período de 25 anos não houve mudanças na distribuição anatômica, porém foi observada redução significativa do subtipo intestinal e aumento do subtipo difuso (P = 0,02). No estrato abaixo de 45 anos foram identificados 39 (11,6%) pacientes, com maior probabilidade de serem do sexo feminino e apresentarem tumor do subtipo difuso em relação ao total da série. CONCLUSÕES: No período de 25 anos, não houve mudanças significativas em relação à idade, distribuição por sexo ou na localização cárdica e não-cárdica do câncer gástrico nesta série de pacientes do sul do Brasil. Ocorreu uma redução significativa do subtipo intestinal e aumento acentuado do subtipo difuso. Nos pacientes abaixo de 45 anos, o câncer gástrico foi mais frequente em mulheres com predomínio do subtipo difuso.

Detecting p53 immunoexpression in esophageal mucosa with exfoliative cytology in individuals at risk for squamous cell carcinoma of the esophagus.

OBJECTIVE: To determine the prevalence of p53 expression in cytologic smear collected by the RS Balloon in high-risk individuals, and test its yield in the cytologic screening of squamous cell carcinoma of the esophagus (SCCE). STUDY DESIGN: Asymptomatic individuals at risk for SCCE underwent esophageal exfoliative cytology with the RS Balloon immediately followed by upper gastrointestinal endoscopy with biopsies of unstained areas after iodine mucosal staining of the esophagus. For each patient, cytologic expression of p53 was compared with the worst endoscopic biopsy diagnosis and the histologic expression of p53. RESULTS: One hundred seventy-one individuals were submitted to the study's protocol. There were 8 lost cases (4.7%) due to inadequate cytologic samples. The final sample consisted of 163 individuals where 150 were male (92%), mean age of 52.6 +/- 12.0 years old. There were 3 cases of dysplasia/SCCE. Immunohistochemical expression of p53 protein was positive in 38 patients (23.6%), with basal layer expression in 29 (76.3%), middle layer expression in 8 (21.1%) and superficial layer in 1 (2.6%). All patients with dysplasia/SCCE had positive immunohistochemical expression of p53 protein. Immunocytochemical expression of p53 protein in cytologic smear was negative in all cytology samples. CONCLUSION: The negative results of immunocytochemical expression of p53 protein suggest that its use does not contribute to improving the performance of conventional cytology of the esophagus in the screening for SCCE and its precursor lesions.

Nutrient patterns and risk of squamous cell carcinoma of the esophagus: a factor analysis in uruguay.

BACKGROUND: Squamous cell carcinoma of the esophagus is a common disease, with an age-standardized incidence rate of 55 cases per 100,000 persons in the northern counties of Uruguay. These rates are comparable to those observed in Iran and China. MATERIALS AND METHODS: In order to contribute to the clarification of the etiology of this lethal disease, a case-control study which included 234 cases and 936 controls, frequency matched for age, sex and residence, was conducted. Factor analysis (principal components) was conducted on the controls and three factors were retained, high-fat, carbohydrates and antioxidants. These nutrient patterns were submitted to multiple logistic unconditional regression in order to estimate the odds ratios of esophageal cancer. RESULTS: The nutrient patterns (labeled as high-fat, carbohydrates and antioxidants) were significantly associated with the risk of esophageal squamous cell cancer. Whereas the high-fat and carbohydrates patterns were directly associated with an increased risk of esophageal cancer, the antioxidants pattern was strongly protective (OR 0.39, 95% CI 0.23-0.66). CONCLUSION: In squamous cell carcinoma of the esophagus an antioxidant dietary pattern is protective, probably due to its action against oxidative stress while high-fat and carbohydrates patterns are associated with an increased risk which may be due to the meat and sodium content, respectively.

High levels of carcinogenic polycyclic aromatic hydrocarbons in mate drinks.

BACKGROUND: Drinking mate has been associated with cancers of the esophagus, oropharynx, larynx, lung, kidney, and bladder. We conducted this study to determine whether drinking mate could lead to substantial exposure to polycyclic aromatic hydrocarbons (PAH), including known carcinogens, such as benzo[a]pyrene. METHODS: The concentrations of 21 individual PAHs were measured in dry leaves of eight commercial brands of yerba mate and in infusions made with hot (80 degrees C) or cold (5 degrees C) water. Measurements were done using gas chromatography/mass spectrometry, with deuterated PAHs as the surrogates. Infusions were made by adding water to the leaves, removing the resulting infusion after 5 min, and then adding more water to the remaining leaves. This process was repeated 12 times for each infusion temperature. RESULTS: The total concentrations of the 21 PAHs in different brands of yerba mate ranged from 536 to 2,906 ng/g dry leaves. Benzo[a]pyrene concentrations ranged from 8.03 to 53.3 ng/g dry leaves. For the mate infusions prepared using hot water and brand 1, 37% (1,092 of 2,906 ng) of the total measured PAHs and 50% (25.1 of 50 ng) of the benzo[a]pyrene content were released into the 12 infusions. Similar results were obtained for other hot and cold infusions. CONCLUSION: Very high concentrations of carcinogenic PAHs were found in yerba mate leaves and in hot and cold mate infusions. Our results support the hypothesis that the carcinogenicity of mate may be related to its PAH content.

pRB expression in esophageal mucosa of individuals at high risk for squamous cell carcinoma of the esophagus.

AIM: To investigate the pRb expression in a large group of patients with history of chronic exposure to the main risk factors for development of squamous cell carcinoma of the esophagus. METHODS: One hundred and seventy asymptomatic individuals at high risk for esophageal squamous cell carcinoma (consumption of more than 80 g of ethanol and 10 cigarettes/d for at least 10 years) underwent upper gastrointestinal endoscopy with biopsies of the esophageal mucosa. As a control group, specimens of esophageal mucosa obtained from 20 healthy subjects were also studied. Immunohistochemical assessment of the tissues was performed using a monoclonal antibody anti-pRB protein. RESULTS: Absence of the pRB staining, indicating loss of RB function, was observed in 33 (19.4%) of the individuals at risk for esophageal cancer, but in none of the healthy controls (P < 0.02). Loss of pRb expression increased in a stepwise fashion according to the severity of the histological findings (P < 0.005): normal mucosa (11/97 or 11.3%), chronic esophagitis (17/60 or 28.3%), low-grade dysplasia (3/10 or 30%), high-grade dysplasia 1/2 or 50%) and squamous cell carcinoma (1/1 or 100%). CONCLUSION: Our findings suggest that abnormal expression of the pRB protein may be implicated in the process of esophageal carcinogenesis. Additional studies are warranted to define the role of the pRB protein as a biomarker for development of esophageal squamous cell carcinoma in individuals at high risk for this malignancy.

The influence of genetic polymorphisms in Ahr, CYP1A1, CYP1A2, CYP1B1, GST M1, GST T1 and UGT1A1 on urine 1-hydroxypyrene glucuronide concentrations in healthy subjects from Rio Grande do Sul, Brazil.

Polymorphisms in genes encoding polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes may alter metabolism of these carcinogens and contribute to inter-individual difference in urine concentrations. We investigated the influence of genetic polymorphism on PAH metabolism in urine from 199 healthy subjects from Southern Brazil. We measured urine 1-hydroxypyrene glucuronide (1-OHPG) concentrations using immunoaffinity chromatography and synchronous fluorescence spectroscopy and genotyped subjects using standard methods. Genetic variants in CYP1B1 (rs1056827, rs1800440, rs10012) were strongly associated with urine 1-OHPG with P-values < 0.010. Variants in aryl hydrocarbon receptor (Ahr) (rs4986826), CYP1A1 (rs1799814) and CYP1A2 (rs2069514) were also, although less strongly, associated with changes in urine 1-OHPG concentrations. These variants had P-values of 0.074, 0.040 and 0.025, respectively. The median urine 1-OHPG concentrations (pmol/ml) in the homozygous wild-type and homozygous variants for CYP1B1 (rs10012) and the Ahr, CYP1A1 and CYP1A2 variants listed above were 2.16 and 0.10, 2.16 and 0.41, 2.03 and 0.46, 2.19 and 2.79, respectively. We found no effect of deletions in GST M1 or GST T1, or different alleles of UGT1A1*28. Adjusting for age, sex, place of residence, tobacco smoke exposure, maté drinking, cachaça and barbeque preparation had only a minor impact on the associations. A model containing just exposure variables had an r2 of 0.21; a model with single genotypes for Ahr, CYP1A1, CYP1A2 and CYP1B1 had an r2 of 0.10; and a model combining both exposure and genotype information had a total r2 of 0.33. Our results suggest that CYP1B1 genotypes are strongly associated with urine 1-OHPG concentrations in this population.

Higher urine 1-hydroxy pyrene glucuronide (1-OHPG) is associated with tobacco smoke exposure and drinking maté in healthy subjects from Rio Grande do Sul, Brazil.

BACKGROUND: The highest rates of esophageal squamous cell carcinoma (ESCC) in Brazil occur in Rio Grande do Sul, the most southern state, which has incidence rates of 20.4/100,000/year for men and 6.5/100,000/year for women. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) through tobacco smoke and other sources may increase the risk of ESCC. The aims of the current study were to investigate the degree and sources of PAH exposure of the inhabitants of this region of southern Brazil. METHODS: Two hundred healthy adults (half smokers, half non smokers, half male and half female) were recruited, given a standardized questionnaire, and asked to provide a urine sample for measurement of 1-hydroxypyrene glucuronide (1-OHPG), a PAH metabolite). Urine 1-OHPG concentrations were measured using immunoaffinity chromatography and synchronous fluorescence spectroscopy and urine cotinine was measured using a dipstick test. We examined factors associated with 1-OHPG concentration using Wilcoxon tests and multiple linear regression. RESULTS: Urine 1-hydroxypyrene glucuronide (1-OHPG) was successfully measured on 199 subjects. The median (interquartile range) of urine 1-OHPG in the 199 participants was 2.09 pmol/mL (0.51, 5.84). Tobacco smoke exposure and maté drinking were statistically significantly associated with higher urine 1-OHPG concentrations in the multivariate linear regression model. CONCLUSION: Tobacco smoke and maté both contribute to high levels of benzo[a]pyrene exposure in the people of southern Brazil. This high PAH exposure may contribute to the high rates of ESCC observed in this population. The increased urine 1-OHPG concentrations associated with maté suggest that contaminants, not just thermal injury, may help explain the increased risk of ESCC previously reported for maté consumption.

p53 immunoexpression: an aid to conventional methods in the screening of precursor lesions of squamous esophageal cancer in patients at high-risk?

INTRODUCTION: Squamous cell carcinoma of the esophagus (SCCE) is diagnosed late and carries a poor prognosis. Lugol chromoendoscopy (LC) has being shown a useful tool in the management of patients at high risk for SCCE. Biomarkers such as p53 protein expression may be present in the esophageal mucosa long before esophageal symptoms or lesions appear and may aid in early diagnosis. This study was carried out to investigate the p53 immunoexpression in esophageal mucosa of smokers and alcohol consumers and study its relationship with different degrees of histological findings and the role of LC to detect areas that express p53. METHODS: Group 1: One hundred and eighty-two asymptomatic subjects at high risk for SCCE (consumption of more than 80 g of ethanol and 10 cigarettes/day for at least 10 years). Group 2: Twenty healthy volunteers who neither smoked nor consumed alcohol. Both groups underwent upper GI endoscopy plus LC, with biopsies of the esophageal mucosa. Expression of p53 protein was compared to histological findings. RESULTS: Group 1: There was 25/182 (14%) Lugol's unstained areas. p53 protein was expressed in a stepwise fashion according to the severity of the histological findings: normal mucosa (12/103 or 12%), mild esophagitis (6/43 or 14%), moderate esophagitis (4/18 or 22%), severe esophagitis (1/3 or 33%), low-grade dysplasia (4/11 or 36%), high-grade dysplasia (2/2 or 100%) and squamous cell carcinoma (2/2 or 100%) (p=0.001). Nine in 25 (36%) patients with Lugol's unstained areas and 22/157 (14%) with normal appearing Lugol's stained mucosa expressed p53. Group 2: There was no Lugol unstained areas. The histological analysis and immunohistochemistry for p53 were normal with the exception of two patients that presented mild esophagitis and expressed p53. Unstained areas were 3.5 times (95% CI: 1.2-9.6) more likely to express p53 then stained ones. Alcoholics/smokers were 1.9 (95% CI: 0.4-8) times more likely to express p53 than non-alcoholics/non smokers. CONCLUSIONS: In this study, we find an association between histological alterations, p53 expression and Lugol's unstained areas. It may point to a higher risk for SCCE. Smokers and alcohol drinkers with normal mucosa or chronic esophagitis that express p53 protein may represent an unrecognized sub-group of individuals that may benefit from surveillance or intervention.

Prevalência do esôfago de Barrett na unidade de endoscopia digestiva de hospital de referência para a região central do Rio Grande do Sul / Prevalence of Barret's esophagus at the digestive endoscopy unit of a reference hospital in the central region of the state of Rio Grande do Sul, Brazil

Introdução: Os dados internacionais sobre a prevalência do esôfago de Barrett(EB) são conflitantes e no Brasil esses dados são escassos. O objetivo deste estudo foi determinar a prevalência do EB no serviço de Endoscopia Digestiva do Hospital Universitário de Santa Maria, RS. Pacientes e métodos: No período de maio de 2002 a junho de 2003 foram estudados de forma consecutiva 1.276 pacientes submetidos à endoscopia digestiva alta. Os pacientes foram examinados atentamente em abusca de irregularidades da linha Z, com auxílio da cromoscopia com lugol, e as alterações sugestivas de EB foram biopsiadas. As secções histológicas foram coradas pelo metódo de HE e alcian-blue pH 2,5. O diagnóstico de EB foi definido pela presença de metaplasia intestinal com alcian-blue positivo. Resultados: Quatorze pacientes apresentaram alterações endoscópicas sugestivas de EB. Em quatro o aspecto era de segmento longo. A histologia confirmou o diagnóstico de metaplasia intestinal especializada em oito pacientes (três com segmento longo e cinco com segmento curto). Do total dos pacientes, 326 (26por cento) realizaram endoscopia por sintomas relacionados à doença do refluxo gastroesofágico (DRGE), a prevalência foi de 2,5 por cento

Uso de midazolam para sedaçäo em endoscopia digestiva alta: estudo comparativo näo encoberto entre as vias intravenosa e sublingual / Use of midazolan for sedation in upper digestive endoscopy: comparative study between intravenous and sublingual route

Os autores compararam a efetividade do midazolam sublingual com o midazolam intravenoso como pré-medicaçao em EDA, envolvendo 80 pacientes divididos em dois grupos. O grau de sedaçao, cooperaçao durante o procedimento e o grau de amnésia após o exame foram comparados, bem como os efeitos na PA, FC e FR, que foram similares para as duas vias de administraçao, com exceçao da amnésia anterógrada, que foi mais efetiva no grupo intravenoso. Concluem que o uso de midazolam sublingual tem efetividade semelhante ao intravenoso, porém com custo menos elevado, determinando maior praticidade na execuçao do procedimento.