Comparative risk of recurrence of dysplasia and carcinoma after endoluminal eradication therapy of high-grade dysplasia versus intramucosal carcinoma in Barrett’s esophagus

Small, Aaron J.; Sutherland, Scott; Hightower, Jessica S.; Guarner-Argente, Carlos; Furth, Emma E.; Kochman, Michael L.; Forde, Kimberly A.; Bewtra, Meenakshi; Falk, Gary W.; Ginsberg, Gregory G.

doi:10.1016/j.gie.2014.10.029

Cited by 33 publications

(18 citation statements)

References 23 publications

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“…Of the 18 full text randomized controlled trials or cohort studies, 4 were considered to be of high quality (3 RFA, 1 SRER), 7 moderate quality (6 RFA studies, and 1 study comparing RFA to SRER), and 7 low quality (7 RFA) as highlighted in Supplemental Table 1 . The majority of the moderate and low quality studies reported recurrence after EET as a secondary analysis; only 7 cohort full text studies (6 RFA and 1 SRER) had recurrence as the primary outcome 27 32 35 36 42 43 44 . The 16 case series and 5 cohort abstracts were all considered to be low quality.…”

Section: Resultsmentioning

confidence: 99%

“…Risk factors for recurrence after RFA therapy were reported in 7 studies (6 manuscripts, 1 abstract) 32 35 40 42 44 45 46 . A single study reported that the presence of erosive esophagitis increased the risk of recurrence on multivariable regression analysis controlling for hiatal hernia length and presence of dysplasia [hazard ratio 15.41 (95 %CI 1.65 – 144.33)] 45 .…”

Section: Resultsmentioning

confidence: 99%

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Recurrence of intestinal metaplasia and early neoplasia after endoscopic eradication therapy for Barrett’s esophagus: a systematic review and meta-analysis

et al. 2017

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Background Conflicting data exist with regard to recurrence rates of intestinal metaplasia (IM) and dysplasia after achieving complete eradication of intestinal metaplasia (CE-IM) in Barrett’s esophagus (BE) patients. Aim (i) To determine the incidence of recurrent IM and dysplasia achieving CE-IM and (ii) to compare recurrence rates between treatment modalities [radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) vs stepwise complete EMR (SRER)]. Methods A systematic search was performed for studies reporting on outcomes and estimates of recurrence rates after achieving CE-IM. Pooled incidence [per 100-patient-years (PY)] and risk ratios with 95 %CI were obtained. Heterogeneity was measured using the I 2 statistic. Subgroup analyses, decided a priori, were performed to explore heterogeneity in results. Results A total of 39 studies were identified (25-RFA, 13-SRER, and 2 combined). The pooled incidence of any recurrence was 7.5 (95 %CI 6.1 – 9.0)/100 PY with a pooled incidence of IM recurrence rate of 4.8 (95 %CI 3.8 – 5.9)/100 PY, and dysplasia recurrence rate of 2.0 (95 %CI 1.5 – 2.5)/100 PY. Compared to the SRER group, the RFA group had significantly higher overall [8.6 (6.7 – 10.5)/100 PY vs. 5.1 (3.1 – 7)/100 PY, P = 0.01] and IM recurrence rates [5.8 (4.3 – 7.3)/100 PY vs. 3.1 (1.7 – 4)/100 PY, P < 0.01] with no difference in recurrence rates of dysplasia. Significant heterogeneity between studies was identified. The majority of recurrences were amenable to repeat endoscopic eradication therapy (EET). Conclusion The results of this study demonstrate that the incidence rates of overall, IM, and dysplasia recurrence rates post-EET are not inconsiderable and reinforce the importance of close surveillance after achieving CE-IM.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Recurrence of intestinal metaplasia and early neoplasia after endoscopic eradication therapy for Barrett’s esophagus: a systematic review and meta-analysis

et al. 2017

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“…Early studies suggested that Barrett's metaplasia recurrence rates after RFA were low, but recent studies have shown much higher recurrence rates, approaching 50% of patients within 4 years in some reports. 44 The origin of these recurrences is not clear, but it seems likely that they result from GORD-induced oesophageal injury that is not entirely prevented by PPI therapy. PPIs, even in high dosages, do not normalise oesophageal acid exposure in many patients with Barrett's oesophagus and bile acid reflux continues despite PPI therapy.…”

Section: Discussionmentioning

confidence: 99%

Aspirin prevents NF-κB activation and CDX2 expression stimulated by acid and bile salts in oesophageal squamous cells of patients with Barrett's oesophagus

Huo

Zhang

et al. 2017

Gut

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Objective In previous studies using oesophageal squamous cells from patients with Barrett's oesophagus (NES-B cells) and from patients without Barrett's oesophagus (NES-G cells), we showed that acid and bile salts induced CDX2 expression only in NES-B cells. CDX2, a transcription factor required to form intestinal epithelium, is a target of NF-κB signaling, which can be inhibited by aspirin. We explored mechanisms underlying differences between NES-B and NES-G cells in CDX2 expression, and effects of aspirin on that CDX2 expression. Design We exposed NES-B and NES-G cells to acid and bile salts, with and without aspirin, and evaluated effects on IκB-NF-κB-PKAc complex activation, p65 NF-κB subunit function, and CDX2 expression. Results In both NES-B and NES-G cells, acid and bile salts activated NADPH oxidase to generate H2O2, which activated the IκB-NF-κB-PKAc complex. NES-B cells exhibited higher levels of phosphorylated IκB and p65 and greater NF-κB transcriptional activity than NES-G cells, indicating greater IκB-NF-κB-PKAc complex activation by acid and bile salts in NES-B cells, and p65 siRNA prevented their increased expression of CDX2. Aspirin blocked IκB phosphorylation, p65 nuclear translocation, CDX2 promoter activation, and CDX2 expression induced by acid and bile salts in NES-B cells. Conclusions Differences between NES-B and NES-G cells in NF-κB activation by acid and bile salts can account for their differences in CDX2 expression, and their CDX2 expression can be blocked by aspirin. These findings might explain why some GORD patients develop Barrett's oesophagus while others do not, and why aspirin might protect against development of Barrett's oesophagus.

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“…Nonetheless, it is well known that EMR improves staging and diagnosis of Barrett’s associated dysplasia, and that nodularity is predictive of underlying higher grade lesion that can be missed on biopsies alone. 37,41,42,43 …”

Section: Discussionmentioning

confidence: 99%

Radiofrequency Ablation Is Associated With Decreased Neoplastic Progression in Patients With Barrett's Esophagus and Confirmed Low-Grade Dysplasia

et al. 2015

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Background & Aims Barrett’s esophagus (BE) with low-grade dysplasia (LGD) can progress to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) has been shown to be an effective treatment for LGD in clinical trials but its effectiveness in clinical practice is unclear. We compared the rate of progression of LGD following RFA to that with endoscopic surveillance alone in routine clinical practice. Methods We performed a retrospective study of patients who either underwent RFA (n=45) or surveillance endoscopy (n=125) for LGD, confirmed by at least 1 expert pathologist, from October 1992 through December 2013 at 3 medical centers in the US. Cox regression analysis was used to assess the association between progression and RFA. Results Data were collected over median follow-up periods of 889 days (inter-quartile range, 264–1623 days) after RFA and 848 days (inter-quartile range, 322–2355 days) after surveillance endoscopy (P=.32). The annual rates of progression to HGD or EAC was 6.6% in the surveillance group and 0.77% in the RFA group. The risk of progression to HGD or EAC was significantly lower among patients who underwent RFA than those who underwent surveillance (adjusted hazard ratio, 0.06; 95% confidence interval, 0.008–0.48). Conclusions Among patients with BE and confirmed LGD, rates of progression to a combined endpoint of HGD and EAC were lower among those treated with RFA than among untreated patients. Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for LGD.

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Comparative risk of recurrence of dysplasia and carcinoma after endoluminal eradication therapy of high-grade dysplasia versus intramucosal carcinoma in Barrett’s esophagus

Cited by 33 publications

References 23 publications

Recurrence of intestinal metaplasia and early neoplasia after endoscopic eradication therapy for Barrett’s esophagus: a systematic review and meta-analysis

Recurrence of intestinal metaplasia and early neoplasia after endoscopic eradication therapy for Barrett’s esophagus: a systematic review and meta-analysis

Aspirin prevents NF-κB activation and CDX2 expression stimulated by acid and bile salts in oesophageal squamous cells of patients with Barrett's oesophagus

Radiofrequency Ablation Is Associated With Decreased Neoplastic Progression in Patients With Barrett's Esophagus and Confirmed Low-Grade Dysplasia

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