Long-term endoscopic surveillance of patients with Barrett's esophagus. incidence of dysplasia and adenocarcinoma: a prospective study

Conio, Mássimo; Blanchi, Sabrina; Lapertosa, G; Ferraris, R.; Sablich, R.; Marchi, Santino; D'Onofrio, V.; Lacchin, Teresa; Iaquinto, Gaetano; Missale, Guido; Ravelli, P.; Cestari, Renzo; Benedetti, G.; Macrì, Giuseppe; Fiocca, Roberto; Munizzi, Francesco; Filiberti, Rosangela

doi:10.1111/j.1572-0241.2003.07666.x

Cited by 192 publications

(72 citation statements)

References 58 publications

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“…However, the natural history of LGD is not well characterized, with rates of progression to HGD or EAC ranging from 10 to 30%, as well as frequent regression to BE (Hameeteman et al, 1989;Weston et al, 1997;O'Connor et al, 1999;Weston et al, 1999Weston et al, , 2001Skacel et al, 2000;Conio et al, 2003). Moreover, histological classification of dysplasia, especially LGD, has high interobserver variability (Alikhan et al, 1999;Montgomery et al, 2001a, b).…”

Section: Discussionmentioning

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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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: Discussionmentioning

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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“…32 The prevalence of BE was lower in women than in men (Table). 7,19,[40][41][42][43][44][45][46][47][48][49][50][51] A systematic review after analyzing the PubMed database between 1997 and 2011 has shown that the prevalence of BE was lower in women than in men (28 out of 10 337, range 0.03-4.6% vs 70 out of 12 463, range 0.08-8.2%).…”

Section: Prevalence Of Barrett's Esophagusmentioning

confidence: 99%

Sex and Gender Differences in Gastroesophageal Reflux Disease

Kim

2016

J Neurogastroenterol Motil

122

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It is important to understand sex and gender-related differences in gastroesophageal reflux disease (GERD) because gender-related biologic factors might lead to better prevention and therapy. Non-erosive reflux disease (NERD) affects more women than men. GERD symptoms are more frequent in patients with NERD than in those with reflux esophagitis. However, men suffer pathologic diseases such as reflux esophagitis, Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) more frequently than women. The prevalence of reflux esophagitis is significantly increased with age in women, especially after their 50s. The mean age of EAC incidence in women is higher than in men, suggesting a role of estrogen in delaying the onset of BE and EAC. In a chronic rat reflux esophagitis model, nitric oxide was found to be an aggravating factor of esophageal injury in a male-predominant way. In addition, the expression of esophageal occludin, a tight junction protein that plays an important role in the esophageal defense mechanism, was up-regulated in women. This explains the male predominance of reflux esophagitis and delayed incidence of BE or EAC in women. Moreover, the symptoms such as heartburn, regurgitation, and extra-esophageal symptoms have been more frequently reported by women than by men, suggesting that sex and gender play a role in symptom perception. Differential sensitivity with augmented symptoms in women might have diagnostic and therapeutic influence. Furthermore, recent studies have suggested that hormone replacement therapy has a protective effect against esophageal cancer. However, an anti-inflammatory role of estrogen remains compelling, which means further study is necessary in this area.

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“…In addition, the diagnosis is often elusive and not confirmed with repeat endoscopy and biopsies [10,11]. In part, this may be due to the high degree of interobserver variability in establishing the diagnosis of low-grade dysplasia, and the variable biopsy sampling protocols by which these patients are followed.…”

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confidence: 99%

Radiofrequency Ablation of Barrett’s Esophagus: Let’s Not Get Ahead of Ourselves

Falk

2010

Dig Dis Sci

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Long-term endoscopic surveillance of patients with Barrett's esophagus. incidence of dysplasia and adenocarcinoma: a prospective study

Cited by 192 publications

References 58 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

Sex and Gender Differences in Gastroesophageal Reflux Disease

Radiofrequency Ablation of Barrett’s Esophagus: Let’s Not Get Ahead of Ourselves

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