J Gastrointest Surg (2012) 16:469–474 DOI 10.1007/s11605-011-1776-3
ORIGINAL ARTICLE
Intraluminal pH and Goblet Cell Density in Barrett’s Esophagus Dimitrios Theodorou & Shahin Ayazi & Steven R. DeMeester & Joerg Zehetner & Christian G. Peyre & Kimberly S. Grant & Florian Augustin & Daniel S. Oh & John C. Lipham & Parakrama T. Chandrasoma & Jeffrey A. Hagen & Tom R. DeMeester
Received: 7 July 2011 / Accepted: 31 October 2011 / Published online: 18 November 2011 # 2011 The Society for Surgery of the Alimentary Tract
Abstract Introduction Goblet cells in Barrett’s esophagus (BE) vary in their density within the Barrett’s segment. Exposure of Barrett’s epithelium to bile acids is a major stimulant for goblet cell formation. The dissociation of bile acids into forms that penetrate Barrett’s epithelium is known to be pH dependent. We hypothesized that variations in the esophageal luminal pH environment explains the variability in goblet cell density. The aim of this study was to correlate esophageal luminal pH with goblet cell density in patients with BE. Methods A customized six-sensor pH catheter was positioned with the most distal sensor in the stomach and the remaining sensors located 1 cm below and 1, 3, 5, and 8 cm above the upper border of the lower esophageal sphincter in five normal subjects and six patients with long-segment BE. The luminal pH was measured by each sensor for 24-h and expressed as median pH. Patients with BE had four quadrant biopsies at levels corresponding to the location of the pH sensors. Goblet cell density was graded from 0 to 3 based on the number per high-power field. Results In normal subjects, the median pH values recorded in the sensors within the lower esophageal sphincter (LES) and esophageal body were all above 5. In patients with BE, the median pH recorded by the sensor within the LES was 2.8 and increased progressively to 4.7 in the sensor at 8 cm above the LES. Goblet cell density was significantly lower in the distal Barrett’s segment exposed to a median pH of 2.2 and increased in the proximal Barrett’s segment exposed to a median pH of 4.4 (p=0.003). Conclusion Patients with BE have a goblet cell gradient that correlates directly with an esophageal luminal pH gradient. This suggests that goblet cell differentiation is pH dependent and likely due to the effect of pH on bile acid dissociation. Keywords Gastroesophageal reflux disease (GERD) . Barrett’s esophagus . Goblet cell . pH gradient D. Theodorou : S. Ayazi : S. R. DeMeester : J. Zehetner : C. G. Peyre : K. S. Grant : F. Augustin : D. S. Oh : J. C. Lipham : J. A. Hagen : T. R. DeMeester Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA P. T. Chandrasoma Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA T. R. DeMeester (*) 1510 San Pablo Street, Suite 514, Los Angeles, CA 90033, USA e-mail:
[email protected]
Introduction A columnar line segment of the esophagus, commonly called Barrett’s esophagus, develops as a consequence of long-standing gastroesophageal reflux disease (GERD). The histology of the columnar segment was first described by Paull and colleagues in 1976.1 They described three types of epithelium contained in the columnar segment: junctional epithelium, which today is known as cardiac epithelium, and two differentiated epithelia—fundic epithelium, which today is known as oxyntocardiac epithelium containing parietal cells, and intestinalized epithelium which today is known as intestinalized cardiac epithelium containing goblet cells. Paull and colleagues noted that the intestinal metaplasia, when present, is always located proximally in the columnar segment and can extend distally
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to the gastroesophageal junction (GEJ) but does not do so in every patient. Why this distribution occurs is not completely understood. Exposure of Barrett’s epithelium to bile acids has been shown to be a major stimulant for goblet cell formation.2 The dissociation of bile salts into forms that penetrate Barrett’s epithelium is pH dependent. We hypothesized that variation in the esophageal luminal pH environment causes the goblet cell density gradient. The aim of this study was to compare the luminal pH at multiple levels in the esophagus of normal subjects and patients with long-segment Barrett’s and correlate esophageal luminal pH with goblet cell density at various levels in patients with Barrett’s esophagus.
J Gastrointest Surg (2012) 16:469–474
USA) as previously described.4 Three characteristics of the LES were assessed: pressure, total length, and abdominal length. When all three components of the LES were normal, the LES was considered as mechanically normal, and when one or more components were abnormal, the LES was considered as mechanically defective.5 Esophageal pH Monitoring Twenty-four-hour esophageal pH monitoring was done in normal subjects and patients with Barrett’s esophagus prior to enrolment into the study. In patients with Barrett’s esophagus, medical therapy was discontinued prior to the study. The pH probe was passed transnasally and positioned 5 cm above the upper border of the manometrically determined LES.
Methods
Multilevel 24-h Esophageal pH Measurement
The Barrett’s group consisted of six prospectively recruited patients (three males, three females) with long-segment Barrett’s esophagus. Their median age was 48 years (range, 37–62) and the duration of their symptom of heartburn ranged from 6 to 20 years. None of the patients had previous foregut surgery. The median length of Barrett’s segment was 8 cm with a range of 6 to 10 cm. All had abnormal esophageal acid exposure on 24-h pH monitoring with a pH sensor placed 5 cm above the lower esophageal sphincter.3 The median (IQR) for the % time pH
