Effect of proton pump inhibitors on markers of risk for high‐grade dysplasia and oesophageal cancer in Barrett’s oesophagus

Hillman, Lybus; Chiragakis, Louise; Shadbolt, Bruce; Kaye, Graham; Clarke, Anthony

doi:10.1111/j.1365-2036.2007.03579.x

Cited by 59 publications

(39 citation statements)

References 30 publications

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“…This may provide additional experimental evidence for the necessity of continued acid suppression. Patients with dysplastic BE are reported to show a reversal of the dysplastic process by proton pump inhibitor therapy; [66][67][68] however, it is unknown if the lesions will reoccur once such a treatment is stopped.…”

Section: Discussionmentioning

confidence: 99%

Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line

Bajpai

Liu

Geng

et al. 2008

Laboratory Investigation

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Barrett's epithelium is a precancerous, specialized columnar metaplasia in the distal esophagus. We demonstrate the changes in cellular phenotype in a non-neoplastic Barrett's cell line (BAR-T), following exposure to acid and bile salt, the two important components of gastroesophageal refluxate. Cell phenotypes in BAR-T cell line were quantified by fluorescence-activated cell sorting (FACS) using monoclonal antibodies against markers: cytokeratin 8/18 (CK8/18) for columnar, CK4 for squamous, mAbDas-1 for colonic epithelial cell phenotype and p75NTR for esophageal progenitors. Cells were exposed for 5 min each day to 200 mM glycochenodeoxycholic acid at pH 4, pH 6 and pH 7.4 or only to acid (pH 4) for up to 6 weeks. The BAR-T cell line comprised 35 ± 5.2% CK8/18, 32 ± 3.5% mAbDas-1, 9.5 ± 3% CK4 and 4 ± 2.5% p75NTR-positive cells. Single exposure to acid and or bile did not change cell phenotypes. However, chronic treatment for at least 2 weeks significantly enhanced (Po0.05) the expression of colonic phenotype and CK8/18-positive cells, as evidenced by FACS analysis. Bile salt at pH 4 and bile salt followed by acid (pH 4) in succession were the strongest stimulators (Po0.01) for induction of colonic phenotype cells. Squamous (CK4 þ ) phenotype did not change by the treatments. Cox-2 expression was induced after acute treatment and increased to twofold during chronic treatment, particularly in response to acidic pH. We conclude that BAR-T cells can be utilized as an 'in vitro' model to study the effect of environmental factors and their influence on the cellular phenotype and molecular changes in the pathogenesis of esophageal cancer.

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Section: Discussionmentioning

confidence: 99%

Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line

Bajpai

Liu

Geng

et al. 2008

Laboratory Investigation

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“…41,42 In addition, in one study, a delay in using a PPI for 2 years or more after diagnosis with BE was associated with an increased risk of developing LGD and an increased risk of developing HGD or EAC. 43 However, other studies have suggested that treatment with PPI or other acid-suppressing drugs was associated with an increased risk of EAC. 44,45 While PPIs may reduce the rate of progression in some patients with BE, they also induce significant hypergastrinemia in a subset of patients by reducing acid-inhibitory feedback pathways.…”

Section: Importance Of Inflammation and Bile Acidsmentioning

confidence: 99%

Barrett esophagus

et al. 2012

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T he incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the western world and accounts for 2% of all cancer-related deaths. The precursor lesion for EAC is Barrett esophagus (BE), which is strongly associated with gastresophageal reflux disease. A major limitation to the study of EAC has been the absence of tractable and genetically modifiable preclinical models of BE. A mouse model of BE and EAC that resembles human disease could provide novel insights into the origins and molecular pathogenesis of BE. In addition, validated animal models could help stratify BE patients given the limited predictive power of current standard endoscopic measures and clinical assessment. Here, we review the findings from recently developed mouse models of BE and EAC and their impact on clinical decision making, surveillance programs and therapeutic options. The data, taken together, suggest potential origins of BE from the gastric cardia, a role of bile acid and hypergatrinemia for carcinogenesis, a growing importance for columnar-like epithelium and a critical role for Notch signaling.

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“…Epidemiological studies have shown that the long-term use of PPIs is associated with lower rates of dysplasia and EAC in patients with BE [122,124,[129][130][131], except for one study [132]. In two other studies, the early use of a PPIs after the diagnosis of BE was associated with a decreased risk of developing dysplasia or EAC [122,129] ( Table 4).…”

Section: Neoplastic Preventionmentioning

confidence: 99%

“…In two other studies, the early use of a PPIs after the diagnosis of BE was associated with a decreased risk of developing dysplasia or EAC [122,129] ( Table 4). The available data are insufficient to draw any definite conclusions [133,134].…”

Section: Neoplastic Preventionmentioning

confidence: 99%

Carcinogenesis of Barrett’s esophagus: a review of the clinical literature

Watari

Oshima

Fukui

et al. 2013

Clin J Gastroenterol

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Barrett's esophagus (BE) is a premalignant condition of esophageal adenocarcinoma (EAC). Although the incidence of BE has risen rapidly in the West, it is rare in Asia despite a recent increase in the prevalence of gastroesophageal reflux disease. Controversies over the definition of BE are presented because most cases show shortsegment BE, especially ultra-short BE, in Asia. Here we review possible risk factors for the development of EAC, particularly possible roles of ethnicity, specialized intestinal metaplasia (SIM), BE length, and environmental factors, such as Helicobacter pylori infection and obesity. Additionally, we summarize recent studies on the effect of chemoprevention including proton pump inhibitors, nonsteroidal anti-inflammatory drugs or aspirin in order to reduce the risk of neoplastic progression in BE patients. Although substantial knowledge of risk factors of dysplasia/EAC in BE is shown, the risk for neoplastic development may be influenced by geographic variation, study population, the presence or absence of SIM or dysplasia at baseline, and the small number of BE patients investigated. Recently, the efficiency of surveillance for BE patients has been discussed from the standpoint of cost-effectiveness. It may be too difficult to draw conclusions because no randomized clinical trials of BE surveillance have been performed.

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Effect of proton pump inhibitors on markers of risk for high‐grade dysplasia and oesophageal cancer in Barrett’s oesophagus

Abstract: SUMMARY BackgroundIt has been shown that the presence on diagnosis of endoscopic macroscopic markers indicates a high-risk group for Barrett's oesophagus.

Cited by 59 publications

References 30 publications

Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line

Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line

Barrett esophagus

Carcinogenesis of Barrett’s esophagus: a review of the clinical literature

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