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Low grade dysplasia in Barrett's esophagus: Should we worry?

ABSTRACT: The optimal management for low-grade dysplasia (LGD) in Barrett's esophagus is unclear. In this article the importance of LGD is discussed, including the significant risk of progression to esophageal adenocarcinoma. Endoscopic surveillance is a management option but is plagued by sampling error and issues of suboptimal endoscopy. Furthermore endoscopic surveillance has not been demonstrated to be cost-effective or to reduce cancer mortality. The emergence of endoluminal therapy over the past decade has resulted in a paradigm shift in the management of LGD. Ablative therapy, including radiofrequency ablation, has demonstrated promising results in the management of LGD with regards to safety, cost-effectiveness, durability and reduction in cancer risk. It is, however, vital that a shared-decision making process occurs between the physician and the patient as to the preferred management of LGD. As such the management of LGD should be "individualised."

SUBMITTER: Jagadesham VP

PROVIDER: S-EPMC4025077 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Low grade dysplasia in Barrett's esophagus: Should we worry?

Jagadesham Vamshi P VP Kelty Clive J CJ

World journal of gastrointestinal pathophysiology 20140501 2

The optimal management for low-grade dysplasia (LGD) in Barrett's esophagus is unclear. In this article the importance of LGD is discussed, including the significant risk of progression to esophageal adenocarcinoma. Endoscopic surveillance is a management option but is plagued by sampling error and issues of suboptimal endoscopy. Furthermore endoscopic surveillance has not been demonstrated to be cost-effective or to reduce cancer mortality. The emergence of endoluminal therapy over the past dec ...[more]

PMID: 24891980

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Project description:BACKGROUND & AIMS:Barrett's esophagus (BE) is the greatest risk factor for esophageal adenocarcinoma (EAC), but only a small proportion of patients with BE develop cancer. Biomarkers might be able to identify patients at highest risk of progression. We investigated genomic differences in surveillance biopsies collected from patients whose BE subsequently progressed compared to patients whose disease did not progress. METHODS:We performed a retrospective case-control study of 24 patients with BE that progressed to high-grade dysplasia (HGD, n = 14) or EAC (n = 10). The control group (n = 73, called non-progressors) comprised patients with BE and at least 5 years of total endoscopic biopsy surveillance without progression to HGD or EAC. From each patient, we selected a single tissue sample obtained more than 1 year before progression (cases) or more than 2 years before the end of follow-up (controls). Pathogenic mutations, gene copy numbers, and ploidy were compared between samples from progressors and non-progressors. RESULTS:TP53 mutations were detected in 46% of samples from progressors and 5% of non-progressors. In this case-control sample set, TP53 mutations in BE tissues increased the adjusted risk of progression 13.8-fold (95% confidence interval, 3.2-61.0) (P < .001). We did not observe significant differences in ploidy or copy-number profile between groups. We identified 147 pathogenic mutations in 57 distinct genes-the average number of pathogenic mutations was higher in samples from progressors (n = 2.5) than non-progressors (n = 1.2) (P < .001). TP53 and other somatic mutations were recurrently detected in samples with limited copy-number changes (aneuploidy). CONCLUSIONS:In genomic analyses of BE tissues from patients with or without later progression to HGD or EAC, we found significantly higher numbers of TP53 mutations in BE from patients with subsequent progression. These mutations were frequently detected before the onset of dysplasia or substantial changes in copy number.

Project description:Background & aimsRadiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barrett's esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE.MethodsWe performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events.ResultsAfter 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan-Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years).ConclusionsIn subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years.

Dataset Information

Low grade dysplasia in Barrett's esophagus: Should we worry?

Publications

Low grade dysplasia in Barrett's esophagus: Should we worry?

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