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: Diagnosis
 

Is reduced esophageal sensitivity in Barrett's patients related to the length of the metaplastic epithelium?

R.M. Bremner, D. Schwartz, P. Crookes (Los Angeles)

There is accumulating evidence in the literature for an altered sensitivity of the columnar lining of Barrett's esophagus. This is thought to be related either to a protective effect of the columnar cells to refluxed acid, or to a change in epithelial nociceptors secondary to reflux damage and the metaplastic epithelial change. Clinically this altered sensitivity is reflected by the "asymptomatic" Barrett's patient who recalls a distant history of severe heartburn. In this situation it is thought that the refluxed damage to the squamous epithelium causes pain or heartburn, but with the metaplastic change to a columnar lining this sensitivity is lost.

The implications of a reduced sensitivity to refluxed gastric juice are profound as the swallow response to refluxed acid may also be blunted. Previously it has been shown that clearance of refluxed gastric acid from the esophagus requires volume clearance by peristalsis induced by a pharyngeal swallow, and then chemical clearance from swallowed saliva which neutralizes remaining esophageal acid. Poor motility results in poor volume clearance [1] and xerostomia results in prolonged esophageal acidification despite normal motility [2]. We have recently shown that the normal response to naturally occurring reflux episodes is to increase the frequency of swallowing [3]. This acts to clear the esophagus of refluxed gastric contents quickly, so that the contact time of the esophageal mucosa with gastric juice is minimized. Acid clearance in patients with Barrett's esophagus is known to be compromised but the reasons for this are not clear. In order to better understand the mechanisms of acid clearance in patients with Barrett's esophagus we applied the new technique of simultaneous ambulatory pH and pharyngoesophageal motility monitoring to a group of endoscopically proven Barrett's patients and compared them to normal volunteers.

Methods

Twelve normal volunteers and 14 patients with Barrett's esophagus were studied. Normal data has previously been published for ambulatory motility using our system [4]. For the purposes of this study the endoscopically measured length of the Barrett's segment was used to group the patients into those with a short columnar segment (SCS) 3-5 cm, nine patients and those with a long columnar segment (LCS, 9-13 cm, five patients). There were no patients with columnar segments between 5 and 9 cm.

After an overnight fast all subjects underwent standard manometry as previously described [5]. After manometry a pH probe (Ingold, Stockholm, Sweden) and an ambulatory motility catheter (Sentron, Amsterdam, The Netherlands) were calibrated and passed transnasally into the esophagus. The ambulatory catheter was placed so that the transducers were at 5, 10, and 15 cm above the lower esophageal sphincter, with a more proximal transducer in the pharynx to flag pharyngeal swallows. Patients were then allowed home to continue with a normal lifestyle. They were instructed to eat two normal meals restricted only by exclusion of acidic foods. Times of eating, lying down to sleep, and rising in the morning were recorded by the subjects during the 24 hour period of study. At the end of the study subjects returned to the laboratory and the data was uploaded from the data recorder to a IBM compatible personal computer. Data were analyzed as previously described (Multigram 6.0z19, Gastrosoft, TX). Analysis of reflux episodes was performed manually by measuring the time from the onset of the reflux episode (pH drop to less than pH 4) to the first swallow, the duration of the reflux episode, and the number of swallows during the episode. From this analysis the average swallow frequency for each reflux episode was calculated. The reflux episodes were further categorized as occurring during the day or during the night. The baseline swallowing frequency was calculated from six randomly chosen 10 minute periods for both the daytime and the nighttime periods that were not within 10 minutes of a reflux episode.

Statistics

Data are expressed as means ± SEM. The Mann-Whitney U test was used to compare differences between groups. Statistical studies were performed with the aid of a computer program (SPSS for windows version 6.0, Chicago, Illinois). Significance was determined at the 5% level (NS denotes not significant).

Results

Overall, the Barrett's patients had a greater number of reflux episodes than normal subjects (49.0 ± 5.41 versus 17.75 ± 4.13, p = 0.0005), longer reflux episodes than normal subjects (mean duration in minutes 4.35 ± 0.67 versus 0.56 ± 0.12, p < 0.0001), and as a consequence, a greater percent time the pH was less than 4 for the 24 hour period (21 ± 4.5% versus 1.24 ± 0.33, p < 0.0001).

Swallow responses to daytime reflux episodes in patients with Barrett’s were compared to responses in normal subjects. Nighttime reflux episodes were compared to daytime episodes in the same patient. This was done because normal subjects had few nocturnal reflux episodes and clearance is known to be prolonged at night when sleeping. Baseline swallowing frequency during reflux free periods was the same for normal subjects and patients with Barrett's esophagus (1.12 ± 0.1 versus 1.1 ± 0.07 swallows/min). Patients with Barrett's esophagus had a diminished swallow response to daytime reflux episodes characterized by a longer time to the first swallow, and a lower swallow frequency (Figures 1 and 2) Nighttime reflux episodes in patients with Barrett's esophagus were characterized by a further blunting of the swallow response (frequency: 2.39 ± 0.18 swallows/minute for the day, versus 1.44 ± 0.27 night, p = 0.02). The number of swallows per reflux episode was increased in patients with Barrett's esophagus (1.7 ± 0.14 versus 3.84 ± 0.5, p = 0.001).

Acid exposure time was greater in patients with LCS than SCS (time below pH 4, 39.2 ± 3.2% versus 12.3 ± 2.46, p = 0.005) despite similar ambulatory motility measurements for amplitude, peristalsis and efficacy. Patients with LCS had a longer delay from the start of a reflux episode to the first swallow than those with SCS (67 ± 14s versus 27 ± 3.6s, p = 0.01), and a lower swallowing frequency during reflux episodes (1.85 ± 0.13sw/min versus 2.39 ± 0.18sw/min, p = 0.02) (Figures 3 and 4). Despite this, the number of swallows per reflux episode was similar for patients with LCS and SCS (3.14 ± 0.36 versus 5.1 ± 1.1, ns).

Figure 1. The average time to the first swallow for the normal subjects and the Barrett's patients during daytime reflux episodes.

Figure 2. The swallowing frequency during reflux for normal subjects and Barrett's patients during daytime reflux episodes.

Figure 3. The average time to the first swallow for the patients with short and long segment Barrett's esophagus.

Figure 4. The difference between the swallowing frequency in patients with long segment and short segment Barrett's esophagus.

Discussion

The clearance mechanisms involved in restoring esophageal pH to normal after naturally occurring reflux episodes in the upright position has not previously been studied in detail. The new technique of simultaneous ambulatory pH and pharyngoesophageal manometry has enabled the investigation into the influence of swallowing frequency on clearance in the upright position. Using this technology we have shown that the normal response to a naturally occurring reflux episodes is to increase the frequency of swallowing. Presumably this response is secondary to afferent feedback from receptors in the esophagus which are sensitive to the noxious quality of the refluxed material. This concept is based on observations showing that acid infusion is associated with greater swallowing rates than water infusions. In the present study we examined three other aspects of the clearance of a reflux episode, i.e. the time to the first swallow after the start of the reflux episode, the frequency of swallowing during the episode, and the number of swallows required for clearance. Patients with Barrett's esophagus exhibited a delayed time to the first swallow compared to normal subjects and an overall decreased frequency of swallowing during the reflux episode. This suggests that the reflex to swallow after esophageal acidification is somewhat depressed in these patients.

We postulated that if acid sensitivity is due to mucosal receptors, then the amount of esophageal mucosal replacement with Barrett's mucosa should be related to the degree of loss of acid sensitivity. For this reason we chose to categorize patients into those with a short columnar segment (< 5cm) and those with a long columnar segment (> 9 cm). The LCS patients had a longer time to the first swallow as well as a lower swallow frequency during reflux. This supports the hypothesis of a progressive destruction of mucosal afferents by the metaplastic process. The swallow response to reflux at night was further depressed in the Barrett's patients. The insensitivity of patients with Barrett's esophagus to nocturnal reflux results in a mucosal exposure to gastric juice for even longer periods than when awake.

This study shows for the first time that there is an additional mechanism responsible for the prolonged esophageal acid exposure seen in patients with Barrett's esophagus. In these patients the swallow response to reflux episodes is defective. Furthermore, this reduced sensitivity to reflux appears to be related to the length of the metaplastic epithelium.

References

1. Helm JF, Dodds WJ, Riedel DR, Teeter BC, Hogan WJ, Arndorfer RC. Determinants of esophageal acid clearance in normal subjects. Gastroenterology 1983;85:607-612.

2. Korsten MA, Rosman AS, Fishbein S. Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury. Am J Med 1991;90:701-705.

3. Bremner RM, Hoeft SF, Costantini M, Crookes PF, Bremner CG, DeMeester TR. Pharyngeal swallowing: the major factor in clearance of esophageal reflux episodes. Ann Surg 1993;218:364-370.

4. Bremner RM, Costantini M, DeMeester TR. Normal esophageal body function: a study using ambulatory esophageal manometry. Am J Gastroenterol 1998;93:183-187.

5. Zaninotto G, DeMeester TR, Schwizer W, et al. The lower esophageal sphincter in health and disease. Am J Surg 1988;155:104-111.


Publication date: August 2003 OESO©2015