p53 protein in esophageal mucosa of individuals at high risk of squamous cell carcinoma of the esophagus.

Squamous cell carcinoma of the esophagus (SCCE) is diagnosed late and carries a poor prognosis. Biomarkers such as p53 protein expression may be present in the esophageal mucosa long before esophageal symptoms or lesions appear and may point toward early diagnosis. Asymptomatic subjects at high risk for SCEE (consumption of more than 80 g of ethanol and 10 cigarettes/day for at least 10 years) underwent upper gastrointestinal endoscopy with biopsies of the esophageal mucosa, and expression of p53 protein was compared with conventional histologic findings. In 182 subjects studied, p53 protein was expressed in a stepwise fashion according to the severity of the histologic findings: normal mucosa (12/103 or 11.7%), mild chronic esophagitis (6/43 or 14%), moderate chronic esophagitis (4/18 or 22.2%), severe chronic esophagitis (1/3 or 33.3%), low-grade dysplasia (4/11 or 36.4%), high-grade dysplasia (2/2 or 100%), and squamous cell carcinoma (2/2 or 100%) (P=0.00025). The odds ratio and confidence intervals were calculated by logistic regression, with multivariate adjustment for potentially confounding variables. The risk for p53 expression was twofold for moderate and severe chronic esophagitis and 10-fold for dysplasia and cancer (P=0.001). p53 protein was expressed not only in cancerous lesions, high-grade and low-grade dysplasia, as expected, but also in mucosa considered normal or with chronic esophagitis using conventional histology. Smokers and alcohol drinkers with normal mucosa or chronic esophagitis that express p53 protein may represent an unrecognized subgroup of individuals that may benefit from surveillance. Follow-up studies of these asymptomatic subjects and molecular analysis of the p53 gene are needed to clarify this point.

[Prevalence of adenocarcinoma of the esophagus and esophagogastric junction in a 10 year period at a cancer referral center in southern Brazil]. / Prevalência de adenocarcinoma do esôfago e da junção esofagogástrica durante 10 anos num centro de referência para câncer no sul do Brasil.

UNLABELLED: There is increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction in the USA and Europe, however, data in Brazil are scanty. OBJECTIVE AND METHODS: We reviewed all histology confirmed esophageal and esophagogastric junction cancer reports during a 10-year period (1987-1996) obtained by upper digestive endoscopy biopsies at a cancer referral center in Southern Brazil. Cancer cases were classified in three categories: adenocarcinoma, squamous cell carcinoma, and others. RESULTS: Among 349 cases, adenocarcinoma was found in 53 (15.2%), squamous cell carcinoma in 283 (81.1%) and others in 13 (3.7%). CONCLUSIONS: In this study, the prevalence of adenocarcinoma was 15%.

Occult dysplasia is disclosed by Lugol chromoendoscopy in alcoholics at high risk for squamous cell carcinoma of the esophagus.

BACKGROUND AND STUDY AIMS: Squamous cell carcinoma of the esophagus (SCCE) becomes symptomatic at a late stage when the disease is already advanced, and this contributes to its poor prognosis. Esophagoscopy of asymptomatic individuals exposed to known risk factors associated with the development of this cancer may facilitate the diagnosis of early cancerous or precancerous lesions; however, conventional esophagoscopy is not accurate enough. The aim of this study was to measure the value of Lugol chromoendoscopy of the esophagus (LCE) as an endoscopic technique to detect dysplasia in patients at risk. PATIENTS AND METHODS: We studied 190 male patients older than 35 attending an outpatient unit for alcoholics who consumed more than 80g of alcohol, more than 10 cigarettes and more than 500 ml 'maté' (a hot infusion of herbs) per day over 10 years. All underwent conventional upper gastrointestinal endoscopy followed by LCE, a spraying of Lugol 3% on the entire esophagus. All patients denied dysphagia. Biopsies were obtained from any unstained areas larger than 5mm and also from stained areas in all individuals. Biopsies were analyzed independently by two pathologists unaware of the biopsy sites. All conventional esophagoscopies showed normal mucosa, except for two suspicious small elevated lesions, confirmed histologically to be SCCE. These two cases were excluded from the statistical analysis. RESULTS: The LCE found unstained areas in 23 patients and a uniformly stained esophageal mucosa in the remaining 165. Biopsies taken from these 23 unstained areas showed dysplasia in six (two high grade and four low grade), and the ones from the 165 stained areas taken at the middle esophagus showed low-grade dysplasia in seven. There was a high prevalence (6.9%) of dysplastic lesions in these individuals and occult dysplasia was significantly more frequent in unstained than stained areas (p = 0.0017). LCE showed a sensitivity of 46%, a specificity of 90%, a positive predictive value of 26% and a negative predicitve value of 96% when unstained areas were compared to stained ones. Agreement between two independent pathologists was high, with a kappa coefficient of 0.64. CONCLUSION: We concluded that individuals who abuse alcohol, smoke and consume 'maté' have a high prevalence of dysplastic lesions that can be better detected by LCE. Esophagi with unstained areas had an eight-fold higher chance of revealing dysplasia than the uniformly stained ones. LCE is an easy and inexpensive method. It improves the detection of dysplasia and should be added to conventional upper GI endoscopy in patients at risk for SCCE.

Esophageal dysplasias are detected by endoscopy with Lugol in patients at risk for squamous cell carcinoma in southern Brazil.

Diagnosis of squamous cell carcinoma of the esophagus is usually late. Staining of the mucosa with Lugol's solution during endoscopy has been suggested to identify early cancer/dysplasia and may improve prognosis. Lugol was tested during endoscopy in 96 asymptomatic subjects at risk for this tumor, who were found to have atypias after exfoliative cytology in southern Brazil. Biopsies were obtained in Lugol's 'stained' and 'unstained' areas in the esophageal mucosa and the histologic results were compared. 'Unstained' areas were present in 64 (66.7%) instances: 44 'unstained' areas over mucosa with normal appearance revealed seven dysplasias (four high and three low grade), whereas 20 'unstained' areas with visible lesions contained only one dysplasia (low grade). 'Stained' areas in 96 (100%) subjects showed two additional dysplasias (one high and one low grade). In this study, Lugol 'unstained' areas were of great value for detection of dysplasias (sensitivity = 80%; specificity = 63%; p = 0.01, Fisher's exact test; CI = 95%; odds ratio = 6.7).

Esophageal dysplasia and chronic esophagitis: detection at upper gastrointestinal tract endoscopy.

UNLABELLED: Cancer of the esophagus becomes symptomatic at an advanced phase with a late diagnosis, when the tumor is already incurable. Early diagnosis has been shown to improve the survival rates. Conventional esophagoscopy is largely available but its sensitivity to detect early cancer or precancerous lesions remains controversial. In this study we tested the sensitivity of conventional esophagoscopy to identify suspicious areas and compared to histopathology of endoscopic biopsies to detect dysplasia and chronic esophagitis in a population at risk for cancer in southern Brazil. Adult males scheduled to have outpatient endoscopy were examined by two experienced endoscopists and any small (< 5 mm) plaque, nodule, erosion, hyperemia and or friable areas of the mucosa were biopsied and looked for the presence of early cancer or precancerous lesions. Normal appearing mucosa at the middle third of the esophagus was also biopsied and results compared for sensitivity, specificity, positive and negative predictive value. Of the 89 individuals with satisfactory biopsies, 3 had dysplasias, 29 moderate or severe chronic esophagitis and 57 normal findings at the histopathological study. We found no early cancer. We found two large, vegetating lesions confirmed to be advanced squamous cell carcinoma but they were excluded from analysis. To detect dysplasia or moderate/severe chronic esophagitis conventional esophagoscopy had a sensitivity of 40.6%, specificity of 78.9%, positive predictive value of 52% and negative predictive value of 70.3. CONCLUSIONS: In this study, conventional esophagoscopy had a low sensitivity to detect dysplasias and/or chronic esophagitis and techniques to improve endoscopic identification of these lesions in individuals at risk for cancer are much needed.