Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Mucosa
 The
 Esophagogastric  Junction
 Barrett's
 Esophagus

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OESO©2015
 
Volume: Barrett's Esophagus
Chapter: Pathophysiology
 

In Barrett's patients, what can be concluded from the continuous measurement of gastric pH over a circadian cycle?

V. Savarino, L. Tessieri, P. Dulbecco (Genova)

Barrett's esophagus is a premalignant condition in which metaplastic specialized columnar epithelium with goblet cells is present in the distal part of the esophagus [1]. The most common type of Barrett's esophagus, the acquired type, is related to increased gastroesophageal acid reflux (GERD), as shown in many studies [2]. The true prevalence of Barrett's esophagus is difficult to determine, but it seems to be about 10% in patients with GERD [3]. However, the reason why some patients with abnormal gastroesophageal acid reflux develop Barrett's esophagus and others do not is unclear. It has been suggested that acid reflux into the esophagus is more pronounced in patients with Barrett's esophagus compared to GERD patients without Barrett epithelium, but this is still controversial [4].

As in other forms of GERD, the pathogenesis is likely multifactorial, and it has been hypothesized that gastric acid hypersecretion could be included among the factors favoring the excessive exposure of esophageal mucosa to acid [5]. However, it is well known that GERD cannot be considered as a disease due to gastric acid hypersecretion. Hirschowitz did not find any difference in the acid and pepsin secretory status of patients with reflux esophagitis and normal subjects, using traditional tests and appropriate controls [6]. So, GERD is not characterized by an excessive amount of gastric acid, in that the main feature is the presence of gastric acid in a wrong place (the esophagus) because of multiple motor abnormalities.

Data gathered on the acid secretory pattern of patients with Barrett's esophagus are scanty and controversial. Some authors [5, 7, 8] showed the existence of gastric acid hypersecretion in patients with reflux esophagitis and Barrett's esophagus. However, Mulholland et al. [5] studied a small group of patients and did not mention whether the presence of duodenal ulcer was absolutely excluded by endoscopy in them. GERD patients with duodenal ulcer are known to secrete more acid than those without this kind of ulceration [9]. Furthermore, the higher proportion of patients with Barrett's esophagus in their small sample of gastroesophageal reflux patients (10 of 17 cases) clearly reflects a referral bias to their investigating center, as acknowledged by the authors themselves.

Also Collen et al. [7, 8] emphasized the existence of greater acid secretion than normal in patients with Barrett's esophagus and GERD. However, most of their patients had basal acid outputs in the range of normal subjects and very few had a basal acid output higher than 15 meq/h, which defines true gastric acid hypersecretion and is in the Zollinger-Ellison range [6]. Moreover, it cannot be again excluded that some of their patients may have suffered from duodenal ulcer, which could have been masked by prior antisecretory therapy.

In contrast with the above studies, Hirschowitz [10] found that gastric acid and pepsin secretion in patients with Barrett's esophagus do not differ from those of appropriately matched controls with esophagitis alone, a population characterized by normal gastric acid and pepsin secretion [6].

All the above-mentioned investigations were done using traditional secretory tests and none measured gastric acidity by means of continuous intragastric pH monitoring. Although this technique ignores the volume of gastric juice and intragastric acidity is the end result of many factors (food, saliva, duodenogastric reflux, gastric emptying, etc.), this is the sole procedure capable of describing the fluctuations of gastric pH over the entire circadian cycle and under near physiological conditions [11]. On the other hand, the concentration of hydrogen ions reported as pH values is a valid parameter to distinguish populations with different grades of acidity. In this light, we investigated hundreds of patients with both gastric and duodenal ulcer using this technique and we confirmed the results of traditional secretory studies, that is there is lower acidity than normal in the former and higher acidity in the latter population [12, 13].

We used this modern and sophisticated technique to study the circadian acidity pattern in 20 patients with well established Barrett's esophagus and compared them to 119 healthy subjects without gastrointestinal symptoms and diseases [14]. Barrett's esophagus was defined endoscopically as the presence of a velvety red gastric-like mucosa lining the distal esophagus for at least 3 cm extending orad from the gastroesophageal junction. Both the tongue-like and the circumferential types of Barrett's esophagus were included. At least four biopsy specimens were taken from the metaplastic epithelium, and the diagnosis was formulated on the basis of histological findings [15]. The two groups were matched for sex and age. We found that the 24-hour median gastric pH profile of patients with Barrett's esophagus was similar to that of controls. In particular, as shown in Table I, there was no difference between their median pH values during the 24-hour period and the daytime, while Barrett patients were significantly less acid during the night (p < 0.05). So, our findings show that the circadian gastric acidity of patients with Barrett's esophagus is similar to that of normal subjects, with the only difference being lower acid values during the second half of the night. This nocturnal elevation of gastric pH could be due to a concomitant chronic atrophic gastritis with consequent acid hyposecretion, but this

Table I. Median (± semi-interquartiles) gastric pH values during different time intervals for patients with Barrett esophagus and controls.

condition was detected in only two of our patients with Barrett's esophagus. An additional more likely explanation can be the existence of duodenogastricreflux, as a recent study has shown that an abnormal increase of duodenal components is real within the stomach of patients with Barrett's esophagus [16].

The lack of gastric acid hypersecretion in patients with Barrett's esophagus might also explain the uncertain role of medical therapy and surgery in inducing regression of Barrett's metaplasia, which is the best conceivable way to reduce the risk of malignant transformation in affected individuals. In fact, previous attempts to reduce the extension of Barrett's esophagus with H2 receptor antagonists have been unsuccessful, whereas antireflux surgery has led to regression in very few patients only [17]. The advent of proton pump inhibitors, antisecretory drugs more potent than H2 antagonists, has recently reopened the issue. Two prospective studies [18,19] indicated that long-term treatment with these powerful drugs may have a therapeutic role in inducing regression of the columnar epithelium. Conversely, in another study [20], lansoprazole, although given in high doses for up to 3 years, did not induce any significant reduction of the metaplastic mucosa. It cannot be excluded that the poor or partial response to powerful antisecretory drugs in terms of reduced length of columnar mucosa in the esophagus in some clinical trials reflects a particular composition of refluxate, that is acid combined with bile salts, in many patients with Barrett's esophagus. However, the precise roles of the different constituents of gastro/duodenal contents are as yet unknown.

In conclusion, the measurement of gastric pH over the circadian cycle shows that gastric hyperacidity is not a unique feature of patients with Barrett's esophagus. The lower acid values registered during the second half of the night may reflect an abnormal duodenogastric reflux. This seems to confirm that acid and pepsin associated with bile salts may be responsible for the development of Barrett columnar epithelium, which does not revert completely to normal even with profound acid suppression obtained by means of powerful high-dose proton pump inhibitors.

References

1. Spechler SJ, Goyal RK. Barrett's esophagus. N Engl J Med 1986;315:362-371.

2. Iascone C, DeMeester TR, Little AG, Skinner DB. Barrett's esophagus, functional assessment, proposed pathogenesis and surgical therapy. Arch Surg 1983;118:543-549.

3. Winters C, Spurling TJ, Chobanian SJ, Curtis DJ, Esposito RL, Hacker JF, Johnson DA, Cruess DF, Cotelingam JD, Gurney MS, Cattau EL. Barrett's esophagus:a prevalent, occult complication of gastroesophageal reflux disease. Gastroenterology 1987;92:118-124.

4. Coenraad M, Masclee AAM, Straathof JWA, Ganesh S, Griffioen G, Lamers CBHW. Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis? Am J Gastroenterol 1998;93:1068-1072.

5. Mulholland MW, Reid BJ, Levine DS, Rubin CE. Elevated gastric acid secretion in patients with Barrett's metaplastic epithelium. Dig Dis Sci 1989;34:1329-1335.

6. Hirshowitz BI. A critical analysis, with appropriate controls, of gastric acid and pepsin secretion in clinical esophagitis. Gastroenterology 1991;101:1149-1158.

7. Collen MJ, Johnson DA. Correlation between basal acid output and daily ranitidine dose required for therapy in Barrett's esophagus. Dig Dis Sci 1992;37:570-576.

8. Collen MJ, Johnson DA, Sheridan MJ. Basal acid output and gastric acid hypersecretion in gastroesophageal reflux disease. Correlation with ranitidine therapy. Dig Dis Sci 1994;39:410-417.

9. Zhu H, Pace F, Sangaletti O, Bianchi Porro G. Gastric acid secretion and pattern of gastroesophageal reflux in patients with esophagitis and concomitant duodenal ulcer. Scand J Gastroenterol 1993;28:387-392.

10. Hirschowitz BI. Gastric acid and pepsin secretion in patients with Barrett's esophagus and appropriate controls. Dig Dis Sci 1996;41:1384-1391.

11. Savarino V, Mela GS, Zentilin P, Malesci A, Vigneri S, Sossai P, Di Mario F, Cutela P, Mele MR, Celle G. Circadian acidity pattern in prepyloric ulcers: a comparison with normal subjects and duodenal ulcer patients. Scand J Gastroenterol 1993;28:772-776.

12. Savarino V, Mela GS, Scalabrini P, Sumberaz A, Fera G, Celle G. 24-hour study of intragastric acidity in duodenal ulcer patients and normal subjects using continuous intraluminal pH-metry. Dig Dis Sci 1988;33:1077-1080.

13. Savarino V, Mela GS, Zentilin P, Mansi C, Vigneri S, Di Mario F, Malesci A, Calabṛ A, Sossai P, Celle G. Circadian acidity pattern in gastric ulcers at different sites. Am J Gastroenterol 1995;90:254-28.

14. Savarino V, Mela GS, Zentilin P, Mele MR, Mansi C, Remagnino C, Vigneri S, Malesci A, Belicchi M, Lapertosa G, Celle G. Time pattern of gastric acidity in Barrett's esophagus. Dig Dis Sci 1996;41:1379-1383.

15. Cameron AJ, Lomboy CT. Barrett's esophagus:age prevalence, and extent of columnar epithelium. Gastroenterology 1992;103:1241-1245.

16. Champion G, Richter JE, Vaezi MF, Singh S, Alexander R. Duodenogastric reflux:relationship to pH and importance in Barrett's esophagus. Gastroenterology 1994;107:747-754.

17. Williamson WA, Ellis FHJr, Gibbs SP, Shuhian DM, Arotz HT. Effect of antireflux operation on Barrett's mucosa. Ann Thorac Surg 1990;49:537-542.

18. Gore S, Healey CJ, Sutton R, Eyre-Brook IA, Gear MW, Shepherd NA, Wilkinson SP. Regression of columnar lined (Barrett's) oesophagus with continuous omeprazole therapy. Aliment Pharmacol Ther 1993;7:623-628.

19. Malesci A, Savarino V, Zentilin P, Belicchi M, Mela GS, Lapertosa G, Bocchia P, Ronchi G, Franceschi M. Partial regression of Barrett's esophagus by long-term therapy with high-dose omeprazole. Gastrointest Endosc 1996;44:700705.

20. Sampliner RE. Effect of up to 3 years of high-dose lansoprazole on Barrett's esophagus. Am J Gastroenterol 1994;89:1844-1848.


Publication date: August 2003 OESO©2015