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Proton pump inhibitors in Barrett's esophagus: Pluripotent but controversial

Protonenpunpemhemmer bei Barrett's Ösophagus

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Zusammenfassung

GRUNDLAGEN: Barrett's Ösophagus (BE) ist die morphologische Komplikation der gastroösophagealen Refluxkkrankheit (GERD) und der wichtigste Risikofaktor für die Entstehung des Adenokarzinoms der Speiseröhre. Die Assoziation zwischen BE und GERD lässt hierbei eine bedeutsame Rolle der ösophagealen Säureexposition vermuten. METHODIK: Übersicht über Protonenpumpenhemmer (PPI)-Therapie bei BE. ERGEBNISSE: Die Onkogenese des Adenokarzinoms von BE über intraepitheliale Neoplasia (Dysplasie) wird noch immer nicht ganz verstanden, aber vermehrte und gestörte Proliferation dürften ein wichtige Faktoren sein. Ex vivo-Experimente und klinische Studie zeigten eine antiproliferative Wirkung der effizienten Säurehemmung auf die intestinale Metaplasia (BE) sowie eine tendenzielle Abnahme der Dysplasieentstehung. Heute werden PPIs erfolgreich im Management der GERD-Symptome eingesetzt, während sie alleine oder im Rahmen eines multimodalen Konzeptes (+endoskopischer Therapie) vielversprechende Therapieansätze erwarten lassen. Dass derzeit eine onkoprotektive Wirkung der PPIs nicht sicher nachgewiesen werden kann, hat möglicherweise auch damit zu tun, dass derzeit viele Patienten eine zu geringe PPI-Dosis erhalten. Da viele Patienten lebenslänglich PPIs benötigen, muss man ihre Nebenwirkungen berücksichtigen und ihren Stellenwert im Vergleich zur chirurgischen Therapie (Fundoplikatio) auswägen. SCHLUSSFOLGERUNGEN: Durch potentiell dauerhafte säurehemmende Wirkung mögen den PPIs eine wichtige Rolle im Langzeit-Management von BE und Ösophaguskarzinom zukommen.

Summary

BACKGROUND: Barrett's esophagus (BE), a significant complication of gastro-esophageal reflux disease (GERD), is the single most important risk factor for esophageal adenocarcinoma. The strong association between BE and chronic GERD suggests that abnormal esophageal acid exposure plays a vital role in this condition. METHODS: Review on PPI treatment for Barrett's esophagus. RESULTS: The progression of BE from specialized intestinal metaplasia to dysplasia and finally invasive carcinoma is incompletely understood, but increased and disordered proliferation is a key cellular event. In both ex vivo experiments and clinical trials in humans, effective acid suppression scales down the proliferative activity of Barrett's metaplasia and the likelihood of dysplasia as well. Today, proton pump inhibitors (PPIs) are almost universally used for the management of reflux symptoms in patients with BE while they may offer many other benefits when used as single agents or in conjunction with pharmacologic or endoscopic therapies. Yet, acid suppression with these drugs may be suboptimal in many patients and their ultimate role in preventing cancer formation has not yet been proven. Because PPIs are life-long therapy for patients with BE, their potential drawbacks need to be reviewed and their relative value need to be balanced when compared to laparoscopic fundoplication. CONCLUSIONS: The ability of PPIs to suppress acid profoundly and consistently may be crucial in the long-term management of BE and esophageal cancer chemoprevention.

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  1. Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA

    G. Triadafilopoulos

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  1. G. Triadafilopoulos
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Correspondence to G. Triadafilopoulos.

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Triadafilopoulos, G. Proton pump inhibitors in Barrett's esophagus: Pluripotent but controversial. Eur Surg 40, 58–65 (2008). https://doi.org/10.1007/s10353-008-0394-0

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