Long-term nonsurgical management of Barrett's esophagus with high-grade dysplasia

Schnell, Thomas; Sontag, Stephen J.; Chejfec, Gregorio; Aranha, Gerard V.; Metz, Adrienne; O’Çonnell, Susan; Seidel, U; Sonnenberg, Amnon

doi:10.1053/gast.2001.25065

Cited by 537 publications

(297 citation statements)

References 15 publications

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“…However, we included these two factors because both are readily ascertainable at the time of endoscopy, making them highly practical in the clinical setting. Fourthly, the combined end point of HGD and EAC is not universal, since regression of HGD has also been reported (Schnell et al, 2001). Even for the combined end point of HGD and EAC, the estimate of the annual progression rate is only 3.3% .…”

Section: Runx3 Mrna Expression Runx3 Msp Value (Nmv)mentioning

confidence: 99%

“…Patients with BE have a 30-125-fold increased risk of developing EAC relative to the general population (Hameeteman et al, 1989). Therefore, regular endoscopic surveillance has been recommended for patients with BE (Sampliner, 2002;Spechler, 2002), and it has been shown that cancers detected in surveillance programs occur at an earlier stage and have a better prognosis (Streitz et al, 1993;Peters et al, 1994;Schnell et al, 2001;Corley et al, 2002). However, endoscopic surveillance has several drawbacks, including its high cost, low yield, and procedure-related risks.…”

Section: Introductionmentioning

confidence: 99%

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Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk

et al. 2005

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Patients with Barrett's esophagus (BE) are at increased risk of developing esophageal adenocarcinoma (EAC). Clinical neoplastic progression risk factors, such as age and the length of the esophageal BE segment, have been identified. However, improved molecular biomarkers predicting increased progression risk are needed for improved risk assessment and stratification. Using realtime quantitative methylation-specific PCR, we screened 10 genes (HPP1, RUNX3, RIZ1, CRBP1, 3-OST-2, APC, TIMP3, p16, MGMT, p14) for promoter hypermethylation in 77 EAC, 93 BE, and 64 normal esophagus (NE) specimens. A subset of genes manifesting significant differences in methylation frequencies between BE and EAC was then analysed in 20 dysplastic specimens. All 10 genes except p14 were frequently methylated in EACs, with RUNX3, HPP1, CRBP1, RIZ1, and OST-2 representing novel methylation targets in EAC and/or BE. p16, RUNX3, and HPP1 displayed increasing methylation frequencies in BE vs EAC. Furthermore, these increases in methylation occurred early, at the interface between BE and low-grade dysplasia (LGD). To demonstrate the silencing effect of hypermethylation, we selected the EAC cells BIC1, in which the HPP1 promoter is natively methylated, and subjected them to 5-aza-2 0 -deoxycytidine (Aza-C) treatment. Real-time RT-PCR indicated increased HPP1 mRNA levels after 3 days of Aza-C treatment, as well as decreased levels of methylated HPP1 DNA. Hypermethylation of a subset of six genes (APC, TIMP3, CRBP1, p16, RUNX3, and HPP1) was then tested in a retrospective longitudinal study of 99 BE and nine LGD specimens obtained from 53 BE patients undergoing surveillance endoscopy. Only highgrade dysplasia (HGD) or EAC were defined as progression end points. Two patient groups were compared: eight progressors (P) and 45 nonprogressors (NP), using Cox proportional hazards models to determine the relative progression risks of age, BE segment length, and methylation events. Multivariate analyses revealed that only hypermethylation of p16 (odds ratio (OR) 1.74, 95% confidence interval (CI) 1.33-2.20), RUNX3 (OR 1.80, 95% CI 1.08-2.81), and HPP1 (OR 1.77, 95% CI 1.06-2.81) were independently associated with an increased risk of progression, whereas age, BE segment length, and hypermethylation of TIMP3, APC, or CRBP1 were not independent risk factors. In combined analyses, risk was detectable up to, but not earlier than, 2 years preceding neoplastic progression. Hypermethylation of p16, RUNX3, and HPP1 in BE or LGD may represent independent risk factors for the progression of BE to HGD or EAC. These findings have implications regarding risk stratification, early EAC detection, and the appropriate endoscopic surveillance interval for patients with BE.

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Section: Runx3 Mrna Expression Runx3 Msp Value (Nmv)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk

et al. 2005

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“…As treatment options broaden for patients with BE-related HGD or intramucosal/superficial submucosal adenocarcinoma, the distinction of these two diagnoses may have clinical significance. In fact, some authors have proposed that esophagectomy be reserved only for those patients in whom cancer can be documented by a biopsy, 27 but these recommendations rest on the assumption that pathologists can reliably distinguish high-grade dysplasia from intramucosal adenocarcinoma in biopsy specimens. Given the fact that lymphatic channels are present within the esophageal mucosa, there is still a small risk of lymph node metastasis, even in patients with intramucosal adenocarcinoma.…”

Section: Be-related Dysplasiamentioning

confidence: 99%

Current issues in Barrett's esophagus and Barrett's-related dysplasia

Goldblum

2015

Modern Pathology

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“…In order for the number of QALYs to be the same whether the natural history model was based on progression through dysplasia, or through the biomarker, the prevalence of the biomarker condition among patients with Barrett's oesophagus must be 33%. No dysplasia to HGD 0.01 37,39,40,42,48 No dysplasia to cancer 0.005 45 LGD to HGD 0.05 37,42,45,47 LGD LGD to no dysplasia 0.63 39,42 HGD to no dysplasia 0.1 42,49 HGD to LGD 0.07 40,42,49 Biomarker + to biomarker ) 0 * Cancer treatment probabilities Resectablity: without surveillance 0.5 5,28,54 Resectablity: with surveillance 0.95 5,28,33 Surgical mortality: without surveillance 0.05 [54][55][56][57] In the best-case scenario, the biomarker-guided oesophagectomy strategy (ME) prevented 76% of cancers, and 93% of cancer deaths compared with OBS. Patients in ME experienced an average 16.707 QALYs at a cost of $2,291 per patient.…”

Section: Natural Historymentioning

confidence: 99%

The cost‐effectiveness of biomarkers for predicting the development of oesophageal adenocarcinoma

Rubenstein

Vakil²,

Inadomi

2005

Aliment Pharmacol Ther

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SUMMARYBackground: The recommended surveillance strategy for oesophageal adenocarcinoma may prevent as few as 50% of cancer deaths. Tissue biomarkers have been proposed to identify high-risk patients. Aim: To determine performance characteristics of an ideal biomarker, or panel of biomarkers, that would make its use more cost-effective than the current surveillance strategy. Methods: We created a Markov model using data from published literature, and performed a cost-utility analysis. The population consisted of 50-year-old Caucasian men with gastro-oesophageal reflux, who were monitored until age 80. We examined strategies of observation only, current practice (dysplasiaguided surveillance), surveillance every 3 months

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Long-term nonsurgical management of Barrett's esophagus with high-grade dysplasia

Cited by 537 publications

References 15 publications

Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk

Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk

Current issues in Barrett's esophagus and Barrett's-related dysplasia

The cost‐effectiveness of biomarkers for predicting the development of oesophageal adenocarcinoma

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