Risk of Malignant Progression in Barrett’s Esophagus Patients: Results from a Large Population-Based Study

Background: Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005.

Subjects and Methods: We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests.

Results: After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P <. 001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P <. 001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P <. 001).

Conclusion: We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective. © The Author 2011. Published by Oxford University Press. All rights reserved.

Increasing incidence of Barrett's oesophagus: a population-based study

Oesophageal adenocarcinoma, a highly fatal cancer, has risen in incidence in Western societies, but it is unclear whether this is due to increasing incidence of its pre-cursor condition, Barrett's oesophagus (BO) or whether the proportion of BO patients undergoing malignant progression has increased in the face of unchanged BO incidence. Data from population-based studies of BO incidence is limited, with equivocal results to date difficult to distinguish from changes in endoscopic practices. The aim of this study was to assess population trends in Barrett's oesophagus (BO) diagnoses in relation to endoscopy and biopsy rates over a 13 year period. The Northern Ireland Barrett's oesophagus Register (NIBR) is a population-based register of all 9,329 adults diagnosed with columnar epithelium of the oesophagus in Northern Ireland between 1993 and 2005, of whom 58.3% were male. European age-standardised annual BO incidence rates were calculated per 100,000 of the population, per 100 endoscopies and per 100 endoscopies including an oesophageal biopsy. Average annual BO incidence rates rose by 159% during the study period, increasing from 23.9/100,000 during 1993-1997 to 62.0/100,000 during 2002-2005. This elevation far exceeded corresponding increases in rates of endoscopies and oesophageal biopsies being conducted. BO incidence increased most markedly in individuals aged <60 years, and most notably amongst males aged <40 years. This study points towards a true increase in the incidence of BO which would appear to be most marked in young males. These findings have significant implications for future rates of oesophageal adenocarcinoma and surveillance programmes. © 2011 Springer Science+Business Media B.V.

Population-based study reveals new risk-stratification biomarker panel for Barrett's esophagus

BACKGROUND & AIMS: The risk of progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is low and difficult to calculate. Accurate tools to determine risk are needed to optimize surveillance and intervention. We assessed the ability of candidate biomarkers to predict which cases of BE will progress to EAC or high-grade dysplasia and identified those that can be measured in formalin-fixed tissues. METHODS: We analyzed data from a nested case-control study performed using the population-based Northern Ireland BE Register (1993-2005). Cases who progressed to EAC (n = 89) or high-grade dysplasia =6 months after diagnosis with BE were matched to controls (nonprogressors, n = 291), for age, sex, and year of BE diagnosis. Established biomarkers (abnormal DNA content, p53, and cyclin A expression) and new biomarkers (levels of sialyl Lewis(a), Lewis(x), and Aspergillus oryzae lectin [AOL] and binding of wheat germ agglutinin) were assessed in paraffin-embedded tissue samples from patients with a first diagnosis of BE. Conditional logistic regression analysis was applied to assess odds of progression for patients with dysplastic and nondysplastic BE, based on biomarker status. RESULTS: Low-grade dysplasia and all biomarkers tested, other than Lewis(x), were associated with risk of EAC or high-grade dysplasia. In backward selection, a panel comprising low-grade dysplasia, abnormal DNA ploidy, and AOL most accurately identified progressors and nonprogressors. The adjusted odds ratio for progression of patients with BE with low-grade dysplasia was 3.74 (95% confidence interval, 2.43-5.79) for each additional biomarker and the risk increased by 2.99 for each additional factor (95% confidence interval, 1.72-5.20) in patients without dysplasia. CONCLUSIONS: Low-grade dysplasia, abnormal DNA ploidy, and AOL can be used to identify patients with BE most likely to develop EAC or high-grade dysplasia.

A population-based association study of SNPs of GSTP1, MnSOD, GPX2 and Barrett's esophagus and esophageal adenocarcinoma

Oxidative stress appears to be important in the pathogenesis of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Single-nucleotide polymorphisms (SNPs) of antioxidant enzyme genes may play a part in determining individual susceptibility to these diseases. The Factors Influencing the Barrett's Adenocarcinoma Relationship (FINBAR) study is a population-based, case-control study of BE and EAC in Ireland. DNA from EAC (n = 207), BE (> or =3 cm BE at endoscopy with specialized intestinal metaplasia on biopsy, n = 189) and normal population controls (n = 223) were analyzed. Several SNPs spanning the genes for glutathione S-transferase P1 (GSTP1), manganese superoxide dismutase (MnSOD) and glutathione peroxidase 2 (GPX2) were genotyped using multiplex polymerase chain reaction and SNaPshottrade mark. The chi(2) test was used to compare genotype and allele frequencies between case and control subjects. Linkage disequilibrium between SNPs was quantified using Lewontin's D' value and haplotype frequency estimates obtained using Haploview. Eleven SNPs were genotyped (six for GSTP1, three for MnSOD and two for GPX2); all were in Hardy-Weinberg equilibrium. None was significantly associated with EAC or BE even before Bonferroni correction. Odds ratios for EAC for individual SNPs ranged from 0.68 [95% confidence interval (CI) 0.43-1.08] to 1.25 (95% CI 0.73-2.16), and for BE from 0.84 (95% CI 0.52-1.30) to 1.30 (95% CI 0.85-1.97). SNPs in all three genes were in strong linkage disequilibrium (D' > 0.887) but haplotype analysis did not show any significant association with EAC or BE. SNPs involving the GSTP1, MnSOD and GPX2 genes were not associated with BE or EAC. Further studies aimed at identifying susceptibility genes should focus on different antioxidant genes or different pathways.

Have patients with esophagitis got an increased risk of adenocarcinoma?:Results from a population-based study

To examine an increased risk of esophageal adenocarcinoma is restricted to patients who develop Barrett's esophagus or whether esophagitis per se is a risk factor for adenocarcinoma.

Cognitive deficits in first-episode psychosis: A population-based study in Sao Paulo, Brazil

Background: Studies conducted in high-income countries have reported significant cognitive deficits in first on set schizophrenia subjects relative to asymptotic controls, and it has been suggested that the severity of such deficits could be directly related to the duration of untreated psychosis (DUP). It is relevant to conduct similar studies in developing countries, given the supposedly better outcome for schizophrenia patients living in the latter environments.

Methods: We applied verbal fluency and digit span tests to an epidemiological-based series of patients with first-onset psychoses (n = 179) recruited in the city of Sao Paulo, and compared the findings with those from non-psychotic control subjects randomly selected from the same geographical areas (n=383).

Results: Psychosis subjects showed lower scores on the three tests relative to controls, with greatest between-group differences for the backward digit span task (p < 0.0001). There were no significant differences between subjects with affective and schizophreniform psychosis. Cognitive performance indices were negatively correlated with the severity of negative symptoms, but showed no relation to DUP.

Conclusion: We found significant cognitive deficits in patients investigated early during the course of psychotic disorders in an environment that is distinct from those where the subjects investigated in previous studies have been drawn from. We found no support to the hypothesis of an association between greater cognitive deficits and a longer DUP. (c) 2006 Published by Elsevier B.V.

Cognitive performance is related to cortical grey matter volumes in early stages of schizophrenia: A population-based study of first-episode psychosis

Background: Neuropsychological deficits have been reported in association with first-episode psychosis (FEP). Reductions in grey matter (GM) volumes have been documented in FEP subjects compared to healthy controls. However, the possible inter-relationship between the findings of those two lines of research has been scarcely investigated.

Objective: To investigate the relationship between neuropsychological deficits and GM volume abnormalities in a population-based sample of FEP patients compared to healthy controls from the same geographical area.

Methods: FEP patients (n = 88) and control subjects (n = 86) were evaluated by neuropsychological assessment (Controlled Oral Word Association Test, forward and backward digit span tests) and magnetic resonance imaging using voxel-based morphometry.

Results: Single-group analyses showed that prefrontal and temporo-parietal GM volumes correlated significantly (p < 0.05, corrected) with cognitive performance in FEP patients. A similar pattern of direct correlations between neocortical GM volumes and cognitive impairment was seen in the schizophrenia subgroup (n = 48). In the control group, cognitive performance was directly correlated with GM volume in the right dorsal anterior cingulate cortex and inversely correlated with parahippocampal gyral volumes bilaterally. Interaction analyses with "group status" as a predictor variable showed significantly greater positive correlation within the left inferior prefrontal cortex (BA46) in the FEP group relative to controls, and significantly greater negative correlation within the left parahippocampal gyrus in the control group relative to FEP patients.

Conclusion: Our results indicate that cognitive deficits are directly related to brain volume abnormalities in frontal and temporo-parietal cortices in FEP subjects, most specifically in inferior portions of the dorsolateral prefrontal cortex. (C) 2009 Elsevier B.V. All rights reserved.

Burnout and behavior-related health risk factors:results from the population-based Finnish Health 2000 study

To explore the relationship between burnout and behavior-related health risk factors.

Mortality in Barrett's oesophagus:Results from a population based study

Background: Patients with Barrett's oesophagus have an increased risk of oesophageal adenocarcinoma but this cancer only accounts for a small proportion of deaths in these patients. Other causes of death are reportedly raised in this group. We examined cause specific mortality among individuals in a population based Barrett's oesophagus register. Methods: We constructed a register of all patients diagnosed with columnar mucosa (including specialised intestinal metaplasia) of the oesophagus within Northern Ireland between 1993 and 1999. Deaths occurring within this cohort until 31 December 2000 were identified and mortality rates were compared with the general population. Results: Overall mortality was not raised in Barrett's patients. During 7413 person years of follow up in 2373 patients there were 253 deaths (standardised mortality ratio (SMR) 96 (95% confidence interval (CI) 84-107)). Mortality from oesophageal cancer was raised in patients with specialised intestinal metaplasia (SMR 774 (95% CI 317-1231 )) but only 4.7% of patients died from this cancer. Mortality from stroke (SMR 65 (95% CI 37-93)) was significantly lower than the general population while mortality from non-cancerous digestive system diseases was significantly higher (SMR 211 (95% CI 111-311)). Mortality rates from all other causes were similar to those of the general population. Conclusions: This study demonstrates that the overall mortality rate in patients with Barrett's oesophagus is closely similar to that of the general population. Oesophageal cancer mortality was raised but is an uncommon cause of death in these patients who also appear to have a reduced risk of death from stroke.