Primary Motility  Disorders of the  Esophagus
 The Esophageal
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 Barrett's
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OESO©2015
 
Volume: The Esophageal Mucosa
Chapter: Alkaline duodenogastric reflux
 

Are there alternative methods for measuring "bile" reflux?

P. Bechi, F. Pucciani, F. Baldini, C. Cortesini (Florence)

Although enterogastric and nonacid gastroesophageal refluxes (GERs) are probably involved in relevant pathologic conditions (gastric ulcer, "chemical" gastritis, severe esophagitis, upper dyspeptic syndromes), none of the different techniques for their detection is completely effective. 99mTc HIDA cholescintigraphy and selenium-homocholic acid taurine scanning are stationary methods and require the consumption of radioactive reflux markers. Other methods involving the assessment of any of the components of enterogastric reflux (e.g., bile acid quantification in the gastric or esophageal aspirates) require what should simply be removed from the stomach or the esophagus, respectively. Monitoring of gastric and/or esophageal pH is almost universally recognized as being unsatisfactory for enterogastric and nonacid GER detection, since it is both an indirect technique and unable to evaluate postprandial periods [1]. Furthermore, all these techniques, with the exception of pH monitoring, are discontinuous and/or restrict data samplings to short periods.

Biases of each of these methods have spurred us to conceive and develop the present ambulatory technique based on the use of a completely new sensor named Bilitec 2000 [2]. The basic working principle of this fiberoptic system is that an absorption peak at = 450 nm (characteristic absorption peak of bilirubin) implies the presence of bilirubin in the sample under consideration [3-5]. Moreover, since the

absorbance (intensity of light absorbed) at a particular wave-length is directly proportional to the concentration of the substance, with absorption at that particular wave-length, the fiberoptic system has the potential to assess bilirubin concentration in a given medium.

The bile reflux monitoring device consists of a probe, as well as a light emitting and signal-elaborating recording unit.

The miniaturized probe, which consists of a flexible fiberoptic bundle, carries the signal into the esophagus or the stomach and back to the optoelectronic unit. Its PVC tip is shaped (Fig. 1).

Two light-emitting diodes (at 470 and 565 nm) represent the sources for the measurement and the reference signals, respectively. The signals are processed by an integrated microcomputer which calculates the difference in the absorbencies at 470 and 565 nm. This value is directly proportional to the bilirubin concentration and, therefore, it is related to bile reflux. At the end of each 24-h monitoring period, the data stored in the buffer of the instrument are transferred to a personal computer for processing and filing.

In vitro studies have shown good precision, good stability, a sensitivity of 2.5 µmol/1 bilirubin concentration, as well as a useful working range of 2.5-100 µmol/l bilirubin concentration (100 µmol/1 bilirubin concentration corresponds to high reflux values).

0051F1.JPG

Figure 1. .The tip of the fiberoptic probe.

0051F2.JPG

Figure 2. .Comparisons of in vivo fiberoptic system measurements (Bil.) with measurements in gastric aspirates of spectrophotometric absorbance (sp.) and bile acid concentration (bile ac.), respectively.

In vivo validation tests were performed on 29 dyspeptic subjects. Due to the lack of a "gold standard" for enterogastric reflux measurement, fiberoptic system absorbance values were compared with values obtained by means of the best methods presently available (i.e., gastric aspiration and 99mTc HID A cholescintigraphy).

All the aspirated samples, when quantitatively sufficient, were homogenized and both analyzed spectrophotometrically and evaluated enzymatically for total bile acid concentration. Bilitec absorbance values, have shown a good correlation with the spectrophotometric (41 samples available) and bile acid concentration (49 samples available) assessment of gastric aspirates (r = 0.63, p < 0.01 and r - 0.71, p < 0.01, respectively; linear correlation). Moreover, fiberoptic system findings were considered to correspond to spectrophotometric and bile acid findings, when they agreed in being above or below conventionally established threshold values. Good concordance was shown (Fig. 2).

Fourteen subjects were studied using the fiberoptic system together with simultaneous 99mTc HIDA cholescintigraphy. In seven of these, both tests showed no reflux, while in six both methods of assessment detected reflux. In one case, bile reflux was detected by cholescintigraphy, but bilimetric assessment failed to detect it. Concordance, as regards the presence/absence of reflux, was significant (p <0.01; binomial test). Figure 3 shows the comparison of results of reflux detection by means of cholescintigraphy and the fiberoptic system. Concordance between the two methods, as far as mucosa/refluxate contact time is concerned, is impressive.

In view of these encouraging results, as a preliminary step for the establishment of normal limits for 24-h monitoring values of gastroesophageal and enterogastric bile reflux, control subjects were studied.

Five healthy volunteers (all males; mean age: 27.4 years, range: 21-36 years) were studied using 24-h esophageal monitoring. Results were compared with those obtained in a group of six subjects with symptoms suggestive of GER (three males, three

0051F3.JPG

Figure 3. .An example of bilimetric (upper) and 99mTc-HIDA cholescintigraphic (lower) tracings. The contact time between refluxate and gastric mucosa agrees in the two methods of measurement.

females; mean age: 62.6 years, range: 43-80 years). The latter group included three subjects with Polya gastrectomy and one with Barrett's esophagus (Fig. 4). The fiberoptic probe was positioned 5 cm above the upper border of the LES (located by manometry) for esophageal monitoring in both volunteers and symptomatic subjects.

Moreover, 5 healthy volunteers (all males; mean age: 27.0 years, range: 26-28 years) were studied for enterogastric reflux (Fig. 5). In these subjects the tip of the probe was positioned fluoroscopically in the stomach between the vertical and the horizontal part of the corpus (Tables 1 and 2).

A greater number of controls will be needed in order to establish cut-off points for normal limits and this represents the next objective.

Conclusions

Bilitec 2000 is the only system at present, available for ambulatory enterogastric reflux and nonacid GER detection. In vitro tests and in vivo validation have demonstrated its reliability, precision and accuracy.

The experience with enterogastric reflux detection is quite satisfactory, and the utilization of the fiber optic system in the study of nonacid GER is even easier and

0051F4.JPG

Figure 4. .Examples of 24-h esophageal tracings from a healthy volunteer (top) and from a symptomatic subject with Barrett's esophagus (bottom).

0051F5.JPG

Figure 5. .Examples of 24-h gastric tracings from a healthy volunteer (top) and from a cholecystectomized subject (bottom).

Table 1. .Values of nonacid GER obtained in control subjects and in symptomatic subjects. Reflux was considered to occur when absorbance detected by the esophageal probe exceeded 0.14 units

Component

Controls (n = 5)

Symptomatic subjects (n = 6)

Mean

SEM

Mean

SEM

Total time (%) Upright time (%) Supine time (%)

0.05 0.06 0.05

±0.03 ±0.05 ±0.02

16.96 13.95 21.68

± 9.91 ± 9.33 ± 13.99

No. of episodes No. of episodes >5 min Longest episode (min)

1.20 0 0.43

±0.73 ±0.12

22.83 4.17 124.47

± 9.48 ± 2.53 ± 74.89

Table 2. .Values of enterogastric reflux obtained in control subjects. Reflux was considered to occur when absorbance detected by the gastric probe exceeded 0.14 absorbance

Controls (n = 5)

Component

Mean

SEM

Total time (%) Upright time (%) Supine time (%)

2.58 1.86 3.53

± 1.07 ±0.93

±2.21

No. of episodes No. of episodes >5 min Longest episode (min)

13.00 1.60 15.80

±5.67 ±0.51 ±7.74

results appear even more reliable (no need for fluoroscopic probe positioning, no displacement during 24-h monitoring). The combined use of the fiber optic probe and pH-monitoring in the esophagus, has shown that the presence of gastric content in the esophagus (i.e., GER can occur with a pH between 4-7) [6,7]. Therefore, it is restrictive to consider reflux as occurring only when esophageal pH drops below 4 (acid reflux with no or negligible enteric component) or - exceptionally - exceeds 7 (alkaline reflux with no or negligible gastric secretion component). Agreement must be reached on the term best fitted to define this reflux, which has been previously defined as "mixed reflux" [8] or "alkalacid" [9]. Probably the best solution is just to abandon the term "alkaline" and to define all GER with pH greater than 4 (upper limit for acid reflux) as nonacid [4,6].

A greater number of normal subjects must be studied in order to identify normal limits for enterogastric and nonacid GER. However, the results which have been obtained to date, give an idea of the entity of the physiological occurrence of these types of reflux.

The only relevant problem with the use of the fiberoptic system in the clinical setting, is that some foods (e.g., those with an absorption close to 450 nm) may affect measurements. A list of foods to be consumed at the three different meals is therefore

given to subjects prior to undergoing 24-h bilimetric monitoring [5], otherwise suitable commercial dietary products can be used. This minor drawback is overcome by the many positive aspects of Bilitec 2000:

- the straightforward basic working principle;

- the naturally occurring marker utilized (bilirubin); and

- the additional advantages linked to optical fibers (miniaturization, safety, low cost).

All these make this system an important device in the study of the functional disorders of the alimentary tract.

References

1. Hostein J, Bost R, Faure H, Lachet B, Fournet J. Valeur diagnostique de la pH-métrie gastrique au cours du reflux duodenogastrique. Gastroenterol Clin Biol 1987;11:206-211.

2. Falciai R, Scheggi AM, Baldini F, Bechi P. USA Patent 1990;4,976,265.

3. Bechi P, Falciai R, Baldini F. Cosi F, Pucciani F. Boscherini S. A new fiber-optic sensor for ambulatory enterogastric reflux detection. In: Katzir A (ed) Fiber Optic Medical and Fluorescent Sensors and Applications, Proc SPIE 1648. Bellingham: SPIE 1992; 130-135.

4. Bechi P, Falciai R, Baldini F, Cosi F, Pucciani F, Travaglini F, Boscherini S. Ambulatory assessment of enterogastric and nonacid gastroesophageal reflux by means of a fiberoptic sensor. Gastroenterology 1992;102:A39.

5. Bechi P, Pucciani F, Baldini F, Cosi F, Falciai R, Mazzanti R, Castagnoli A, Passeri A, Boscherini S. Long-term ambulatory enterogastric reflux monitoring. Validation of a new fiberoptic technique. Dig Dis Sci 1993:38:1297-1306.

6. Bechi P, Falciai R, Baldini F, Pucciani F, Cortesini C. A new fiber-optic sensor for detection and measurement of duodenogastric and nonacid gastroesophageal reflux Fourth World Cong ISDE, Chicago, 1989.

7. Champion G, Singh S, Bechi P, Richter JE. Duodenogastric reflux. Relationship to esophageal pH and response to omeprazole. Gastroenterology 1993;104:A51.

8. Cortesini C, Pucciani F. Usefulness of combined gastric and esophageal pH monitoring in detecting gastroesophageal alkaline and mixed reflux Eur Surg Res 1984; 16:378-382

9. Mattioli S, Pilotti V, Felice V, Lazzari A. Zannoli R, Bacchi ML, Loria P, Tripodi A, Gozzetti G. Ambulatory 24-hr pH monitoring of esophagus, fundus and antrum. A new technique for simultaneous study of gastroesophageal and duodeno-gastric reflux. Dig Dis Sci 199035:929-938.


Publication date: May 1994 OESO©2015