Proton Pump Inhibitors Reduce the Risk of Neoplastic Progression in Patients With Barrett's Esophagus

Kastelein, Florine; Spaander, Manon; Steyerberg, Ewout W.; Biermann, Katharina; Valkhoff, Vera E.; Kuipers, Ernst J.; Bruno, Marco J.

doi:10.1016/j.cgh.2012.11.014

Cited by 182 publications

(156 citation statements)

References 27 publications

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“…However, even in patients without refl ux symptoms, in whom BE is incidentally found during evaluation of other symptoms and/or signs, the use of PPIs deserves consideration. Several cohort studies now suggest that subjects with BE maintained on PPI therapy have a decreased risk of progression to neoplastic BE compared with those with either no acid suppressive therapy or those maintained on H 2 RA therapy ( 57,(137)(138)(139). In addition, the risk profi le of these medications is favorable in most patients, and the cost of this class of drugs has diminished substantially in recent years because of the availability of generic forms of the medications.…”

Section: Summary Of Evidencementioning

confidence: 99%

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Shaheen

Falk

Iyer

et al. 2016

American Journal of Gastroenterology

1,336

1,412

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Recent population studies suggest that gastroesophageal refl ux disease (GERD) is increasing in prevalence, both in the United States and worldwide ( 1,2 ). Th e diagnosis of GERD is associated with a 10-15% risk of Barrett's esophagus (BE), a change of the normal squamous epithelium of the distal esophagus to a columnar-lined intestinal metaplasia (IM). Risk factors associated with the development of BE include long-standing GERD, male gender, central obesity ( 3 ), and age over 50 years ( 4,5 ). Th e goal of a screening and surveillance program for BE is to identify individuals at risk for progression to esophageal adenocarcinoma (EAC), a malignancy that has been increasing in incidence since the 1970s ( 6,7 ).Th e purpose of this guideline is to review the defi nition and epidemiology of BE, available screening modalities for BE detection, rationale and methods for surveillance, and available treatment modalities including medical, endoscopic, and surgical techniques. In order to evaluate the level of evidence and strength of recommendations, we used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system ( 8 ). Th e level of evidence ranged from "high" (implying that further research was unlikely to change the authors' confi dence in the estimate of the eff ect) to "moderate" (further research would be likely to have an impact on the confi dence in the estimate of eff ect) to "low" (further research would be expected to have an important impact on the confi dence in the estimate of the eff ect and would be likely to change the estimate) or "very low" (any estimate of eff ect is very uncertain). Th e strength of a recommendation was graded as "strong" when the desirable eff ects of an intervention clearly outweighed the undesirable eff ects and as "conditional" when there was uncertainty about the tradeoff s. We used meta-analyses or systematic reviews when available, followed by clinical trials and cohort and case-control studies. In order to determine the level Barrett's esophagus (BE) is among the most common conditions encountered by the gastroenterologist. In this document, the American College of Gastroenterology updates its guidance for the best practices in caring for these patients. These guidelines continue to endorse screening of high-risk patients for BE; however, routine screening is limited to men with refl ux symptoms and multiple other risk factors. Acknowledging recent data on the low risk of malignant progression in patients with nondysplastic BE, endoscopic surveillance intervals are attenuated in this population; patients with nondysplastic BE should undergo endoscopic surveillance no more frequently than every 3-5 years. Neither routine use of biomarker panels nor advanced endoscopic imaging techniques (beyond high-defi nition endoscopy) is recommended at this time. Endoscopic ablative therapy is recommended for patients with BE and high-grade dysplasia, as well as T1a esophageal adenocarcinoma. Based on recent level 1 evidence, endoscopic ablative therapy is ...

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Section: Summary Of Evidencementioning

confidence: 99%

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Shaheen

Falk

Iyer

et al. 2016

American Journal of Gastroenterology

1,336

1,412

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“…Several therapeutic interventions, aiming to reduce tumor acidity through administration of alkaline buffers (200 mM sodium bicarbonate), claim to have raised the extracellular pH (pHe) without altering the intracellular pH (pHi) (19), to have reduced lung metastasis (20), and suppressed the formation of spontaneous prostate tumors (21). In addition, several groups have found that treatment with proton pump inhibitors reduced neoplastic development of esophageal adenocarcinoma and hepatoblastoma (22,23). Other reports however, have suggested that acidosis inhibits cancer cell proliferation, induces stress response and apoptosis (24)(25)(26)(27), and reduces activation of Akt, whose upregulation is frequently correlated with poor prognosis (28).…”

Section: Introductionmentioning

confidence: 99%

Bleb formation is induced by alkaline but not acidic pH in estrogen receptor silenced breast cancer cells

Khajah

Mathew

Alam-Eldin

et al. 2015

International Journal of Oncology

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Abstract.De novo and acquired resistance to endocrinebased therapies in breast cancer occurs in parallel with epithelial to mesenchymal transition (EMT), which is associated with enhanced proliferative and metastatic potential, and poor clinical outcome. We have established several endocrine insensitive breast cancer lines by shRNA-induced depletion of estrogen receptor (ER) by transfection of MCF7 cells. All of these exhibit EMT. We have previously reported that brief exposure of specifically ER -breast cancer cells, to extracellular alkaline pH, results in cell rounding and segregation, and leads to enhanced invasive potential. In this study we describe more detailed morphological changes and compare these with cell exposure to acidic pH. Morphological changes and localization of various molecules critical for cell adhesion and motility, associated with pH effects, were assessed by live cell microscopy, electron microscopy, and immunofluorescence. Exposure of either ER -or ER + breast cancer cells to extracellular acidic pH did not induce significant changes in morphological appearance. Conversely, brief exposure of specifically ER silenced cells, to alkaline pH, resulted in cell contractolation and formation of bleb-like actin-rich structures which were evenly distributed on the outer membrane. Integrin α2, FAK, and JAM-1 were found in the cytoplasm streaming into the newly formed blebs. These blebs appear to be related to cell polarity and movement. Pre-treatment with cytochalasin-D or inhibitors of Rho or MLCK prevented both contractolation and bleb formation. Our data suggest that the effect of pH on the microenvironment of endocrine resistant breast cancer cells needs to be more extensively investigated. Alkaline, rather than acidic pH, appears to induce dramatic morphological changes, and enhances their invasive capabilities, through re-organization of cortical actin.

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“…However, the authors noted that the association was likely better explained by the fact that the underlying condition for PPI use (i.e., GERD) was itself a risk factor for the development of EAC (34). On the other hand, other prospective and retrospective cohort studies have concluded that PPIs may be protective in patients with BE (35,36). A systematic review and metaanalysis of 7 observational (five cohort and two casecontrol) studies showed that PPI use was associated with a 71% risk reduction of EAC or HGD in individuals with BE, with a trend towards a dose-response relationship (37).…”

Section: Acid Suppressionmentioning

confidence: 99%

Barrett’s esophagus: best practices for treatment and post-treatment surveillance

Mansour

El–Serag

Anandasabapathy

2017

Ann. Cardiothorac. Surg.

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Barrett's esophagus (BE) is a premalignant condition that increases the risk of esophageal adenocarcinoma (EAC). Significantly more common in the Western world, risk factors include increased age, male sex, white race, gastro-esophageal reflux disease (GERD), central obesity, and cigarette smoking. The rates of progression to cancer depend on the grade of Barrett's dysplasia. Screening for BE is recommended in patients with GERD and additional risk factors. Endoscopic surveillance of patients with BE likely improves overall outcomes. Advanced endoscopic imaging can help increase the efficiency of current endoscopic surveillance.Endoscopic therapy is safe and effective for the treatment of dysplastic BE and intramucosal EAC, but ongoing surveillance following treatment is necessary. This review will cover screening, surveillance, advanced imaging, chemoprevention, endoscopic treatment, and post-treatment surveillance of BE.

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Proton Pump Inhibitors Reduce the Risk of Neoplastic Progression in Patients With Barrett's Esophagus

Cited by 182 publications

References 27 publications

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Bleb formation is induced by alkaline but not acidic pH in estrogen receptor silenced breast cancer cells

Barrett’s esophagus: best practices for treatment and post-treatment surveillance

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