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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 & aimsBarrett'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.MethodsWe 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.ResultsTP53 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).ConclusionsIn 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:IntroductionEndoscopic eradication therapy with radiofrequency ablation (RFA) and endoscopic mucosal resection is a safe and effective treatment for Barrett's esophagus. Although the outcomes of surveillance endoscopy after successful endoscopic eradication therapy have been described, no previous studies have modeled the natural history or the effect of surveillance endoscopy after successful ablation to prevent progression to invasive esophageal adenocarcinoma.MethodsThe US RFA Registry is a multicenter registry consisting of patients treated with RFA for Barrett's esophagus at 148 institutions (113 community-based and 35 academic-affiliated). The authors fit models to impute the natural history of recurrence and neoplastic progression after any recurrence or retreatment. Natural history estimates of invasive adenocarcinoma after ablation therapy were compared with as-treated estimates at 5 years to derive the preventive risk difference for surveillance.ResultsNatural history estimates for the postablation progression of high-grade dysplasia (HGD) or intramucosal adenocarcinoma to invasive adenocarcinoma after treatment were 6.3% at 5 years compared with 1.3% for low-grade dysplasia (LGD). The natural history model found a much higher preventative risk difference for surveillance for HGD/intramucosal adenocarcinoma (-4.8%), compared with LGD (-1.1%). The numbers needed to surveil at 5 years were 21 and 90 for these groups, respectively, to prevent one case of invasive esophageal adenocarcinoma, making surveillance after successful ablation of baseline HGD more than 4 times as effective at preventing invasive cancer than after successful ablation of baseline LGD.DiscussionEndoscopic surveillance after successful ablation of baseline HGD or intramucosal cancer is much more effective than surveillance after successful treatment of baseline LGD in averting invasive adenocarcinoma. Although the modest benefits of surveillance for treated LGD may be greater than the risks for patients at average risk for adverse effects of endoscopy, clinicians should concentrate on retaining patients with baseline HGD or cancer in endoscopic surveillance programs.

Project description:Background and aimsBarrett's esophagus with low-grade dysplasia (BE-LGD) carries a risk of progression to Barrett's esophagus with high-grade dysplasia (BE-HGD) and esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) appears to be a safe and efficacious method to eradicate Barrett's esophagus. However, a confirmed consensus regarding treatment of BE-LGD with RFA vs. endoscopic surveillance is lacking. Therefore, this study aimed to elucidate the efficacy and safety for RFA vs. endoscopic surveillance in decreasing the risk of BE-LGD progression to BE-HGD or EAC.MethodsRelevant studies published before May 1, 2021 were identified by searching relevant medical databases. The primary outcome was the rate of progression BE-LGD to HGD and/or EAC after treatment with RFA and endoscopic surveillance. The secondary outcome was the rate of complete eradication of dysplasia (CE-D) and complete eradication of intestinal metaplasia (CE-IM) after treatment with RFA and endoscopic surveillance. Adverse events were also extracted and evaluated.ResultsThree randomized controlled trials were eligible for analysis. The pooled estimate of rate of neoplastic progression of BE-LGD to HGD or EAC was much lower in the RFA group than the endoscopic surveillance group (RR, 0.25; 95% CI, 0.07-0.93; P = 0.04), with moderate heterogeneity (I2 = 55%). Subgroup analysis based on progression grade was performed. The pooled rate of progression of BE-LGD to HGD was much lower in the RFA group than the endoscopic surveillance group (RR, 0.25; 95% CI, 0.07-0.71; P = 0.01), with low heterogeneity (I2 = 15%). Although the pooled risk of progression of BE-LGD to EAC was slightly lower in the RFA group than the endoscopic surveillance group (RR, 0.56; 95% CI, 0.05-6.76), the result was not statistically significant (P = 0.65). RFA also was associated a higher rate of CE-D and CE-IM both at the end of endoscopic treatment and during follow-up. However, the rate of adverse events was slightly higher after RFA treatment.ConclusionRFA decreases the risk of BE-LGD progression to BE-HGD. However, given the uncertain course of LGD and the potential for esophageal stricture after RFA, treatment options should be fully considered and weighed.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021266128, identifier PROSPERO (CRD42021266128).

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

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

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