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

doi:10.1016/j.cgh.2012.11.014

Clinical Gastroenterology and Hepatology

Volume 11, Issue 4, April 2013, Pages 382-388

https://doi.org/10.1016/j.cgh.2012.11.014 Get rights and content

Background & Aims

Acid exposure contributes to the development of Barrett's esophagus (BE) and its progression toward esophageal adenocarcinoma. Patients with BE are frequently treated with acid suppressants, but it is unclear whether these prevent the development of BE-related cancer. We investigated whether acid suppression reduces the risk of neoplastic progression in patients with BE.

Methods

We performed a multicenter prospective cohort study of 540 patients with BE. We collected information on medication use at each surveillance visit, which was cross-checked with pharmacy records. Patients also completed a questionnaire about their use of over-the-counter medication. Incident cases of high-grade dysplasia and esophageal adenocarcinoma were identified during a median follow-up period of 5.2 years. Time-dependent Cox regression models were used to investigate the effect of acid suppression on the risk of neoplastic progression.

Results

Forty patients (7%) developed high-grade dysplasia or esophageal adenocarcinoma during the follow-up period. Use of histamine-2 receptor antagonists did not affect the incidence of neoplastic progression. However, use of proton pump inhibitors (PPIs) at inclusion in the study or during the follow-up period reduced the risk of neoplastic progression (hazard ratio, 0.41; 95% confidence interval, 0.18–0.93 and hazard ratio, 0.21; 95% confidence interval, 0.07–0.66). Prolonged use of PPIs and good adherence were associated with an additional protective effect. The prevalence of esophagitis decreased during PPI use, but length of BE was not affected.

Conclusions

In a multicenter prospective cohort study, PPI use was associated with a reduced risk of neoplastic progression in patients with BE.

Section snippets

Study Design

We conducted a multicenter prospective cohort study in 3 academic and 12 regional hospitals in the Netherlands (Appendix 1). Between November 2003 and December 2004, 756 patients were included with known or newly diagnosed BE. The endoscopic diagnosis was confirmed by the presence of intestinal metaplasia. We excluded patients with BE shorter than 2 cm, patients who had antireflux surgery, and patients with a history of high-grade dysplasia (HGD) or EAC. Incident cases of HGD or EAC were

Patient Characteristics

A total of 540 BE patients were included in this study and followed for a median duration of 5.2 years (interquartile range [IQR], 3.5–5.7). Patients had a median age of 60.5 years at inclusion, and 386 patients (71%) were male. During follow-up 28 patients developed HGD, and another 12 patients developed EAC. The annual incidence of HGD and EAC combined was 1.6% (95% confidence interval [CI], 1.1–2.1), and the annual incidence of EAC alone was 0.5% (95% CI, 0.2–0.8). The risk of neoplastic

Discussion

In this large prospective cohort study, PPI use was associated with a 75% reduction in the risk of neoplastic progression in patients with BE, independent of age, gender, BE length, esophagitis, histology, and use of other medications. H₂RA use did not affect the risk of neoplastic progression.

This is a methodologically sound prospective study that shows that PPIs strongly reduce the risk of neoplastic progression in BE. The protective effect of PPIs increased with prolonged use and good

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Cited by (169)

Assessment of the Relationship Between Gastric-Acid Suppressants and the Risk of Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis
2023, Current Therapeutic Research - Clinical and Experimental
Esophageal cancer is a cancerous tumor that develops in the esophagus. It is the 10th most common cancer and has a low survival rate. Esophageal adenocarcinoma (EAC) is increasing in incidence globally. Those with EAC are affected by Barrett's esophagus metaplasia, which is attributed to genetic predisposition and is more common in men. Studies suggest that gastric acid suppressants, like proton pump inhibitors and histamine-2 receptor antagonists, have anticancer properties and reduce EAC. However, other research has suggested that they are not cancer-protective, and the use of antisecretory drugs is a risk factor for developing EAC.
This systematic review and meta-analysis investigated the properties and risk factors associated with using gastric acid suppressants in patients with EAC.
This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Information from selected articles, including the lead author's name, year of publication, study setting, sample size, and gender, was extracted and recorded into an Excel (Microsoft, Redmond, Washington) form. Statistical data included odds ratio, hazard ratio, and/or risk ratio, with a 95% CI associated with patients with EAC and receiving gastric acid suppressants. Data were compared with individuals not receiving treatment. Publication bias was assessed using Begg's and Egger's tests. Statistical analyzes used Stata 14.0 (Stata LLC, College Station, Texas).
The initial electronic literature search retrieved 3761 titles/abstracts. Extensive screening selected 20 articles for analysis. Odds ratios associated with EAC in the individuals using gastric acid suppressants were 0.77 (95% CI, 0.49–1.22; P = 0.274) and 0.67 (95% CI, 0.39–1.29; P = 0.240) for proton pump inhibitors and 1.02 (95% CI, 0.44-2.36; P = 0.967) for histamine-2 receptor antagonists.
The results found that gastric acid suppressants do not have a protective role in EAC and are not risk factors. Future studies of confounding variables and risk factors are needed to understand what affects EAC development.
The path(ology) from reflux oesophagitis to Barrett oesophagus to oesophageal adenocarcinoma
2022, Pathology
This review seeks to summarise the steps in the path from reflux oesophagitis to Barrett oesophagus to oesophageal adenocarcinoma. The epidemiology, clinical presentation, definitions, pathological features, diagnostic pitfalls, and emerging concepts are reviewed for each entity. The histological features of reflux oesophagitis can be variable and are not specific. Cases of reflux oesophagitis with numerous eosinophils are difficult to distinguish from eosinophilic oesophagitis and other oesophagitides with eosinophils (Crohn's disease, medication effect, and connective tissue disorders). In reflux oesophagitis, the findings are often most pronounced in the distal oesophagus, the eosinophils are randomly distributed throughout the epithelium, and eosinophilic abscesses and degranulated eosinophils are rare. For reflux oesophagitis with prominent lymphocytes, clinical history and ancillary clinical studies are paramount to distinguish reflux oesophagitis from other causes of lymphocytic oesophagitis pattern. For Barrett oesophagus, the definition remains a hotly debated topic for which the requirement for intestinal metaplasia to make the diagnosis is not applied unanimously across the globe. Assessing for dysplasia is a challenging aspect of the histological interpretation that guides clinical management. We describe the histological features that we find useful in making this evaluation. Oesophageal adenocarcinoma has been steadily increasing in incidence and has a poor prognosis. The extent of invasion can be overdiagnosed due to a duplicated muscularis mucosae. We also describe the technical factors that can lead to challenges in distinguishing the mucosal and deep margins of endoscopic resections. Lastly, we give an overview of targeted therapies with emerging importance and the ancillary tests that can identify the cases best suited for each therapy.
Quality in Barrett's Esophagus: Diagnosis and Management
2022, Techniques and Innovations in Gastrointestinal Endoscopy
The field of Barrett's esophagus has been flourishing with major advances in quality clinical practices and technological innovations in both diagnosis and treatment. Gaps in the current screening practices have the potential to be addressed with novel nonendoscopic screening platforms. The foundation for diagnosis and detection in Barrett's esophagus is a high-quality endoscopic examination. These exam components can be summarized as the 5 L's: to identify and document Landmarks, measure and document Length of the Barrett's segment; to Look for subtle irregularities with careful inspection; to document and target visible Lesions; and finally assess each Level of Barrett's segment for occult or subtle dysplastic abnormalities using a protocol such as Seattle protocol. Key tools in endoscopic surveillance are a high-resolution endoscope and either chromoendoscopy with acetic acid or virtual chromoendoscopy. Available adjunctive techniques for detection include other enhanced endoscopic imaging, wide area transepithelial sampling, and tissue-based biomarkers, and artificial intelligence is just on the horizon. Endoscopic eradication therapy is now positioned as the standard strategy for high grade dysplasia and intramucosal carcinoma in Barrett's esophagus in an organ sparing approach. Selected patients with confirmed low-grade dysplasia may also benefit from treatment. Tissue acquiring approaches include endoscopic mucosal resection and endoscopic submucosal dissection. Nontissue acquiring modalities include radiofrequency ablation, cryotherapy, and hybrid APC. This comprehensive review details best practices for diagnosis and treatment in Barrett's esophagus and highlights innovations that are poised for the clinical arena.
Antireflux and Endoscopic Therapies for Barrett Esophagus and Superficial Esophageal Neoplasia
2021, Surgical Clinics of North America
Revisiting Proton Pump Inhibitors as Chemoprophylaxis Against the Progression of Barrett’s Esophagus
2023, Current Gastroenterology Reports
Management of Long-Segment Barrett's Esophagus
2023, Journal of Laparoendoscopic and Advanced Surgical Techniques

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: Conflicts of interest The authors disclose no conflicts.

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Original articleAlimentary tractProton Pump Inhibitors Reduce the Risk of Neoplastic Progression in Patients With Barrett's Esophagus

Background & Aims

Methods

Results

Conclusions

Section snippets

Study Design

Patient Characteristics

Discussion

Gastroenterology

Clin Gastroenterol Hepatol

Am J Gastroenterol

Clin Gastroenterol Hepatol

Gastroenterology

Am J Gastroenterol

Gastroenterology

Am J Gastroenterol

Gastrointest Endosc

Gastroenterology

Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study

Gut

Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age

J Natl Cancer Inst

American Gastroenterological Association medical position statement on the management of Barrett's esophagus

Gastroenterology

New British Society of Gastroenterology (BSG) guidelines for the diagnosis and management of Barrett's oesophagus

Gut

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