Acid suppression therapy in Barrett's esophagus: the importance of pH monitoring.

It is generally accepted that intestinal metaplasia of the esophageal mucosa results from chronic injuries caused by acid gastroesophageal reflux (GER). It would seem to follow, therefore, that appropriate therapy of Barrett’s esophagus, once recognized, should attempt to eliminate any continuing esophageal acid exposure. Indeed, the usual standard of care in this disease includes the use of potent acid-suppressing medications (or surgery) in an attempt to accomplish this goal. Such therapies have been well documented to result in resolution of the patient’s reflux symptoms and healing of associated esophagitis. There is, however, no present evidence that either of these therapeutic approaches results in regression of the metaplastic epithelium or elimination of the malignant potential in this disease. The observation that patients with Barrett’s esophagus have a decreased sensitivity to esophageal acid exposure indicates that control of heartburn in these patients does not ensure the absence of continuing acid reflux [1]. This possibility was initially documented by the study from our laboratory using ambulatory intra-esophageal pH monitoring, which showed that Barrett’s patients rendered asymptomatic on omeprazole frequently were having continued abnormal GER [2]. Subsequently, this phenomenon was better clarified by the observation that recovery of gastric acidity overnight, so-called “nocturnal acid breakthrough” occurs with high frequency even with twice-daily dosing of omeprazole [3]. These observations form the basis for the suggestion that long-term control of GER in patients with Barrett’s esophagus requires monitoring of intragastric and distal esophageal pH during the time when the patient is undergoing therapy. This concept has gained acceptance by many clinical investigators in this field. Does continuing acid reflux, even in diminished amount, constitute a threat to the patient with Barrett’s esophagus? The first suggestion that this might be true was provided by cell culture studies from esophageal biopsies of patients with Barrett’s esophagus showing that in vitro exposure to pulses of acid resulted in greater proliferation and less differentiation of the metaplastic epithelium [4]. A subsequent study by the same investigators provided the clinical link to the in vitro experiments. Using ambulatory pH monitoring during therapy with proton pump inhibitors (PPI) to establish the presence or absence of control of GER, these investigators documented that patients with continuing abnormal GER showed greater evidence of proliferation activity and less differentiation from their endoscopic biopsies than did patients with well-controlled GER [5]. Thus, experimental evidence both at the basic and clinical level supports the need for ambulatory pH monitoring to establish adequacy of acid suppression therapy and to guide titration of medication dosing in these patients. Does dose adjustment based on pH monitoring result in evidence of regression of the abnormal metaplastic epithelium in Barrett’s esophagus patients? Two recent clinical observations suggest an affirmative answer to this question. Our approach to patients with Barrett’s esophagus has been to use pH monitoring to adjust