Does this patient have Barrett's esophagus? The utility of predicting Barrett's esophagus at the index endoscopy

OBJECTIVES: Few studies have evaluated the ability of the endoscopist to predict the presence of Barrett's esophagus (BE) at index endoscopy. The goals of this study were to determine the operating characteristics of endoscopy in diagnosing BE, and to determine the clinical and endoscopic predictors of BE in suspected BE patients at the index endoscopy. METHODS: From September 1993 to October 1997, endoscopic reports were examined to identify patients with suspected BE. All esophageal pathology reports during the same period were evaluated for the presence of specialized intestinal metaplasia. RESULTS: During the study period, 4053 endoscopies were performed on 2393 patients. Eight percent of all procedures were performed for suspected or confirmed BE. Fifty-three patients were known to have BE and thus their reports were excluded from this analysis. Five hundred seventy of the remaining patients had esophageal biopsies performed, and were included in this analysis. Among these 570 patients, 146 were suspected to have BE on endoscopy, while 424 were not suspected to have BE at the time of endoscopy. There were no differences among the two groups in terms of gender, race, and dyspepsia as an indication for the endoscopy. However, suspected BE patients were slightly younger and were more likely to have heartburn, but were less likely to have dysphagia as an indication for the endoscopy. The sensitivity and specificity of the endoscopists' assessments were 82% (95% confidence interval [CI], 72-92) and 81% (95% CI, 78-84), respectively. The positive predictive value and the negative predictive value were 34% and 97%, respectively. The positive likelihood ratio was 4.32 (95% CI, 3.49-5.31) and the negative likelihood ratio was 0.22 (95% CI, 0.13-0.38). Univariate analysis showed that endoscopists diagnosed BE in those with long-segment BE (LSBE) more accurately than in those with short-segment BE (SSBE) (55% vs 25% p = 0.001; odds ratio [OR] = 3.63, 95% CI, 1.71-7.70). Barrett's esophagus was correctly diagnosed in 38.5% of white patients but in only 14.7% of black patients (p = 0.01; OR = 3.63, 95% CI, 1.31-10.13). Multivariable logistic regression identified only the length of the columnar-appearing segment (p = 0.002; OR = 3.33, 95% CI, 1.54-7.17) and race (p = 0.08; OR = 2.31, 95% CI, 0.88-6.03) to be associated with the presence of BE on biopsy. CONCLUSIONS: Barrett's esophagus is frequently suspected at endoscopy; SSBE was more frequently suspected than LSBE, but was correctly diagnosed only 25% of the time, versus 55% for LSBE. Endoscopists diagnosed BE with a sensitivity of 82% and a specificity of 81%. However, the positive predictive value was only 34%, whereas the negative predictive value was 97%. The length of the columnar-appearing segment is the strongest predictor of BE at endoscopy. Alternative methods are needed to better identify BE patients endoscopically, especially those with SSBE.     

From GERD to Barrett's esophagus: Is the pattern in Asia mirroring that in the West?

Gastroesophageal reflux disease (GERD) is a known predisposing factor for Barrett's esophagus. Amongst individuals with symptomatic GERD, the prevalence of Barrett esophagus is estimated to be more than 10%, and an individual with Barrett's esophagus is more likely than the general population to develop esophageal adenocarcinoma. In Western Europe and North America, incidence of esophageal adenocarcinoma had been on the upward trend for many decades. In comparison, although the prevalence of GERD and reflux esophagitis has increased several fold in some parts of Asia, the prevalence of esophageal adenocarcinoma and Barrett's esophagus remains generally low in the region. Rising incidence of esophageal adenocarcinoma has been observed in regions witnessing increasing prevalence of GERD. If the recent increase in prevalence of GERD in parts of urbanized Asia is any indication of the beginning of an upsurge in the incidence of Barrett's esophagus and associated adenocarcinoma, would we be witnessing a pattern of epidemiological shift mirroring that in the West? Given that more than 90% of Barrett's esophagus in Asian patients is of the short‐segment type, which is reported to have lesser propensity to develop to adenocarcinoma, could the ongoing epidemiologic transition take Asia on the same trail as that which the West has taken? This article will draw on relevant findings from various parts of Asia and take an in‐depth look at prevailing disease trends to see where Asia stands now in the changing epidemiology of GERD, Barrett's esophagus and associated adenocarcinoma.     

Heat shock changes the heterogeneity distribution in populations of Caenorhabditis elegans: does it tell us anything about the biological mechanism of stress response?

In this paper we analyze survival data of populations of sterilized nematodes, Caenorhabditis elegans, exposed to heat shocks of different duration at the beginning of their adult lives. There are clear hormesis effects after short exposure to heat and clear debilitation effects after long exposure. Intermediate durations result in a mixture of these two effects. In this latter case, the survival curves for the control and experimental populations intersect. We show that observed effects may be explained by using a model of discrete heterogeneity. According to this model, each population of worms in the experiment is a mixture of subcohorts of frail, normal, and robust individuals; exposure to heat changes the initial proportion of worms in the subcohorts (heterogeneity distribution); and these changes depend on the duration of exposure. In other words, exposure to heat does not influence mortality rates (survival functions) in the subcohorts but does cause individuals to move from one subcohort to another. In a biological interpretation of this finding we hypothesize that, when coping with stress, the organisms of worms use several lines of defense. Switching these lines on and off in response to stress in individual organisms generates the spectrum of observed survival effects at the population level. We discuss possible molecular biological mechanisms of stress response and directions for further research.     

What is the role of endoscopy and oesophageal biopsies in the management of GERD?

Gastroesophageal reflux disease (GERD) is a diagnosis applicable to “all individuals who are exposed to the risk of physical complications from gastroesophageal reflux, or who experience clinically significant impairment of health related well being (quality of life) due to reflux related symptoms, after adequate reassurance of the benign nature of their symptoms”. It remains, predominantly, a symptom-based diagnosis, confirmed clinically by a response to acid suppression therapy although it is accompanied by demonstrable increases in acid exposure on esophageal pH-metry and by endoscopic and histological changes. Standard white light endoscopy permits diagnosis of erosive reflux disease (ERD) which, if present, should be graded for severity using the Los Angeles classification system. However, the role of endoscopy in clinical practice is, primarily, to evaluate patients with persistent symptoms, despite medical therapy, or to investigate alarm features and exclude complications such as Barrett’ oesophagus which should be assessed using the Prague C & M criteria. Newer endoscopic techniques allow detection of ‘minimal change’ GERD lesions and Barrett's oesophagus-associated dysplastic or neoplastic lesions; however, none of the newer techniques has been validated for routine clinical practice. There is an increasing recognition that histology in GERD may provide useful diagnostic information, in part to exclude other lesions, such as eosinophilic oesophagitis, intestinal metaplasia and dysplasia or malignancy and, in part, to identify changes, such as basal cell hyperplasia, papillary elongation and, most recently, dilated intercellular spaces, that are consistent with GERD. However, more widespread incorporation of histology into the clinical management of GERD will require a standardized biopsy protocol and efforts to minimise interobserver differences in the identification of GERD-related histological changes.     

Barrett's esophagus and reflux esophagitis: is there a missing link?

OBJECTIVES: Barrett's esophagus (BE) is associated with esophageal reflux. The development stage of BE is not well described. Epidemiological evidence indicates that the columnar epithelium in BE is acquired and reaches its full length rapidly. We tested the hypothesis that BE might result from direct replacement of erosions in reflux esophagitis (RE). METHODS: At endoscopy, we compared the length and distribution of esophageal erosions in 50 patients with RE with the length and distribution of columnar epithelium in 50 patients with BE. RESULTS: The median length of erosions in RE was 2 cm, less than the median length of columnar epithelium in BE, 5 cm (p < 0.001). Erosions in RE were usually multiple and scattered, involving the entire circumference of the esophagus in only 10% of cases, but circumferential involvement by columnar epithelium was found in 68% of BE cases (p < 0.001). Circumferential involvement, 3 cm or longer, was found in 0% of cases of RE versus 56% of BE cases (p < 0.001). Two patients without RE or BE had large areas of epithelial loss of uncertain etiology. CONCLUSIONS: The length and distribution of erosions in RE differ greatly from the length and distribution of columnar epithelium in BE. It is unlikely that BE arises directly from areas of esophagitis. We suggest that BE may develop after loss of a long segment of squamous epithelium, with columnar replacement in the presence of continuing acid reflux.     

Is there publication bias in the reporting of cancer risk in Barrett's esophagus?

BACKGROUND & AIMS: The published risk of adenocarcinoma in the setting of Barrett's esophagus (BE) varies. Publication bias, the selective reporting of studies featuring positive or extreme results, may result in overestimation of this cancer risk in the literature. The aim of this study was to assess those publications reporting a cancer risk in BE for evidence of publication bias. METHODS: A MEDLINE search for all published estimates between 1966 and 1998 of cancer risk in BE was performed. All studies reporting a cancer risk expressible in cancers per patient-year of follow-up were retrieved. Bibliographies of these studies were surveyed for additional estimates. All publications that required an initial endoscopy with histologic confirmation of BE and any cancer were included. The relationship of reported cancer risk to size of the study was assessed. Multivariable regression controlling for differences in definition of BE, as well as other study characteristics, was performed. The data were also analyzed by means of a funnel diagram, an epidemiologic method to assess publication bias. RESULTS: Five hundred fifty-four abstracts were reviewed. Twenty-seven publications met the stated criteria for inclusion. There was a strong correlation between cancer risk and the size of the study, with small studies reporting much higher risks of cancer than larger studies. This association persisted when differences in the definition of BE, retrospective vs. prospective nature of the study, surveillance interval, and the effect of cancer detected in the first year were considered. The funnel diagram analysis suggested publication bias. CONCLUSIONS: The cancer risk in BE may be overestimated in the literature due to publication bias.     

What can modeling tell us about the threat of antiviral drug resistance?

PURPOSE OF REVIEW: Currently, antiviral resistance is a major public health concern. Here, we review how mathematical models have been used to provide insights into the emerging threat of antiviral resistance. We focus mainly on the problem of drug resistance to HIV. RECENT FINDINGS: We review how antiviral models of HIV have been used: (1) to understand the evolution of an epidemic of drug-resistant HIV, (2) to predict the incidence and prevalence of drug-resistant HIV, (3) to conduct biological 'cost-benefit' analyses, and(4) to make public health policy recommendations. We also briefly discuss antiviral resistance for HSV-2 and influenza. Recent studies indicate that for HSV-2 and influenza drug resistance is not likely to become a major public health problem. However, for HIV the situation is very different. Results from several studies predict that a high prevalence of drug-resistant HIV will be an inevitable consequence of more widespread usage of antiretroviral therapies (ART). However more widespread usage of ART will save a substantial number of lives, and could even result in epidemic eradication. SUMMARY: Models have been used in many ways to provide insight into the emerging threat of antiviral resistance, particularly for HIV. At this stage in the HIV epidemic the most important future use of models may be that they will force the goals of public health policies to be clearly defined. Once goals have been defined it can then be decided whether a high prevalence of drug-resistant HIV is a threat or simply a justified means to an end.     

What can genetics tell us about the cause of fixed airflow obstruction?

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide with smoking being the most important risk factor of the disease. However, lung function and COPD are known to also have a genetic component and a deeper knowledge of the genetic architecture of the disease could lead to further understanding of predisposition to COPD and also to development of new therapeutic interventions. Genetic linkage studies and candidate gene association studies have not provided evidence to convincingly identify the genes underlying lung function or COPD. However, recent large genome-wide association studies (GWAS) including tens of thousands of individuals have identified 26 variants at different loci in the human genome that show robust association with quantitative lung function measures in the general population. A growing number of these variants are being shown to be associated with COPD. Following the identification of these new lung function loci, the challenge now lies in refining the signals to identify the causative variants underlying the association signals and relating these signals to the molecular pathways that underlie lung function.     

Early identification of radiographic osteoarthritis of the hip using an active shape model to quantify changes in bone morphometric features: Can hip shape tell us anything about the progression of osteoarthritis?

Objective

Few methods exist to measure the progression of osteoarthritis (OA) or to identify people at high risk of developing OA. Striking radiographic changes include deformation of the femoral head and osteophyte growth, which are usually measured semiquantitatively following visual assessment. In this study, an active shape model (ASM) of the proximal femur was used to determine whether morphologic changes to the bone could be quantified and used as a marker of hip OA.

Methods

One hundred ten subjects who had no signs of radiographic hip OA at baseline (Kellgren/Lawrence [K/L] scores 0–1) were selected from the Rotterdam Study cohort of subjects ages ≥55 years. To measure the progression of OA, subjects were followed up with radiographic assessment after 6 years. At the 6‐year followup, 55 subjects had established OA (K/L score 3), and in 12 of these OA subjects, the progression of the disease required a total hip replacement (THR). Age‐ and sex‐matched control subjects had a K/L score of 0 at followup. Using the ASM, subjects were assessed for shape changes in the femoral head and neck before, during, and after the development of radiographic OA. Scores of shape variance, or mode scores, were assigned for 10 modes of variation in each subject, and differences in mode scores were determined.

Results

During followup, significant changes in shape of the proximal femur occurred within the OA group from baseline to followup (P < 0.0001 for mode 1 and P = 0.002 for mode 6) but not within the control group. At baseline (all subjects having K/L scores 0–1), there were significant differences in mode 6 between the OA group and the control group (P = 0.020), and in modes 3 and 6 between the OA subjects who underwent THR and the remaining OA subjects (P = 0.012 and P = 0.019, respectively).

Conclusion

Compared with traditional scoring methods, the ASM can be used more precisely to quantify the deforming effect of OA on the proximal femur and to identify, at an earlier stage of disease, those subjects at highest risk of developing radiographic OA or needing a THR. The ASM may therefore be useful as an imaging biomarker in the assessment of patients with hip OA.