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The lower esophageal sphincter in health and disease
The Lower Esophageal Sphincter in Health and Disease Giovanni Zaninotto, MD, Tom R. DeMeester, MD, Wemer Schwizer, MD, KarI-Erik Johansson, MD, and Shih-Chuan Cheng, PhD, Omaha, Nebraska
T h e function of the lower esophageal sphincter is to protect the esophageal mucosa from excessive exposure to gastric juice. Clinical and in vitro studies have shown t h a t the sphincter's ability to perform this function is d e p e n d e n t on the resistance it imposes to the flow of gastric juice from an environm e n t above atmospheric pressure, the stomach, into an e n v i r o n m e n t below atmospheric pressure, the esophagus. This resistance is due to the integrated mechanical effect of sphincter pressure, overall length and the length exposed to the positive envir o n m e n t a l pressure of the a b d o m e n [1]. Each of these components can be measured by esophageal m a n o m e t r y . F r o m a clinical perspective, mechanical incompetency of the sphincter occurs when o n e or more of these components fail. T h e purpose of this s t u d y was to d e t e r m i n e the normal percentile values for these c o m p o n e n t s and identify the level differentiating a mechanically c o m p e t e n t sphincter f r o m an i n c o m p e t e n t sphincter. T o accomplish this, esophageal m a n o m e t r y was used to measure these sphincter components in normal subjects and a population of patients with s y m p t o m s suggestive of gastroesophageal reflux. T h e latter were divided into those with normal and abnormal esophageal exposure to acid gastric juice based on 24 hour esophageal p H monitoring and t h e n stratified on t h e basis of their m a n o m e t r i c m e a s u r e m e n t s according to the percentile values obtained from the normal subjects. T h e percentile at which the incidence of reflux statistically increased identified the m a n o m e t r i c values for sphincter pressure, abdominal length, and overall length t h a t characterize a mechanically i n c o m p e t e n t sphincter.
From the Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska. Supportedin part by Health Future Foundation, Omaha, Nebraska. Requests for reprints should be addressed to Tom R. DeMeester, ME), Department of Surgery, Creighton University School of Medicine, 601 North 30th Street, Omaha, Nebraska 68105. Presented at the 28th Annual Meeting of the Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 12 and 13, 1987.
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Patients and Methods The normal population consisted of 50 volunteers who did not have a history of foregut symptoms; upper gastrointestinal disease; or previous esophageal, gastric, duodenal, or biliary surgery. All showed normal results on upper gastrointestinal roentgenographic barium studies, esophageal manometry, and 24 hour esophageal pH monitoring according to previously published standards [4]. There were 19 men and 31 women with a mean age of 35.8 4- 10.3 years (median 33 years, range 23 to 71 years), and a mean body weight of 70.3 + 14.7 kg (median 68 kg, range 47.6 to 131 kg). Each subject signed an informed consent form and all studies were performed at Creighton University Surgical Gastrointestinal Diagnostic and Research Center. The patient population consisted of 622 patients with foregut symptoms who were referred for evaluation over a 10 year period between 1977 and 1987; 430 to the University of Chicago and 192 to Creighton University. Patients who were under the age of 15 or who had undergone previous esophageal or gastric surgery were not included. There were 295 men and 327 women with a mean age of 47.6 4- 19.6 years (median 50 years, range 15 to 82 years). All underwent esophageal manometry and 24 hour esophageal pH monitoring at one of the institutions. Manometry was performed using a single catheter assembly consisting of five fluid-filled, perfused polyvinyl tubes bonded together with five 0.8 mm lateral openings placed 5 cm apart and radially oriented 120 degrees from each other. The recording catheter was continuously perfused with distilled water by way of a low-compliance, pneumohydraulic capillary infusion pump (Arndorfer Medical Specialties, Greendale, WI) at a rate of 0.5 ml/ rain [2I. Each tube was connected to an external pressure transducer (model P2306, Statham transducer, Gould, Cleveland, OH) positioned at the midaxillary level. Before each test, the pressure transducers were calibrated using a mercury-filled manometer so that a change in pressure of 1 mm Hg corresponded to 0.5 mm on the recording paper. The pressure wave forms generated were printed by a Gould ES1000 16 channel recorder on paper running at a velocity of 5 mm/s. A belt pneumograph
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(Hewlett-Packard) was positioned around the chest to record respiratory excursions. A piezoelectric transducer was taped on the neck at the level of the cricoid cartilage to record pharyngeal swallows. Manometry was performed in the fasted state and all medications were discontinued 24 hours before the test. The subject was placed in the supine position and encouraged to relax. The recording catheter was passed through an anesthetized nostril into the stomach, and withdrawn at 1 cm increments every 20 seconds back into the esophagus. The three manometric characteristics of the distal esophageal sphincter measured were sphincter pressure, abdominal length, and overall length (Figure 1). The end respiratory gastric baseline pressure was used as a zero reference for pressure measurement. A persistent rise in pressure exceeding 2 mm Hg above the gastric baseline marked the distal border of the sphincter. The proximal border was marked by the point where sphincter pressure dropped to end inspiratory esophageal baseline pressure. Five measurements of the distance between these two points were averaged and represented the overall length of the sphincter. The point at which the end inspiratory pressure changed from a positive to a negative deflection represented the respiratory inversion point. Five measurements of the distance between the respiratory inversion point and the distal border of the sphincter, that is, the length of the pressure wave that reflected positive excursions with respiration, were averaged and represented the abdominal length of the sphincter. The amplitude of the sphincter was measured as the difference (in mm Hg) between the gastric baseline and the pressure at the respiratory inversion point during the middle of the respiratory cycle. Five measurements of sphincter pressure were obtained and averaged in order to obviate the variation of pressures at each orifice due to the radial asymmetry of the sphincter [3]. Esophageal pH monitoring was performed using a glass electrode and a portable solid state monitor which sampled and stored esophageal pH at 6 second intervals. The probes were calibrated in a standard buffer solution at a pH of 7 and a pH of I before and after monitoring. The pH probe was passed transnasally and positioned 5 cm above the upper border of the distal esophageal sphincter measured by manometry. The patient or volunteer was sent home and instructed to remain in the upright or sitting position until he or she retired for the evening, to avoid strenuous exertion, and to follow a diet restricted to three meals and composed of food with a pH between 5 and 7. Only water was permitted between meals. A diary was kept of food and fluid intake, symptoms experienced during the monitored period, the time a supine position was assumed in preparation for sleep, and the time of rising in the morning. At the end of the test the stored data were transferred to an IBM personal computer and analyzed using a commercial software program (Gastrosoft| Dallas, TX). Acid reflux was defined as whenever the pH in the esophagus dropped to 4 or less. The amount of esophageal
Volume 155, January 1988
Overall Length r
-~
Gastric Base Line Pressure 4'3 -
~ ~ I1, ,~/l/[lll/~ I ~ , . . "
4~2 1() Sec
4'1
40
~9 'ff ~VVV,!/vv~./ I 38 3'70m RIP j Esophageal Abdominal Length Base Line Pressure
Figure 1. A sample manometric measurement of the lower esophageal sphincter. RIP = respiratory inversion point,
acid exposure was scored using a previously published mathematical formula based on the mean value and standard deviation for six components of the 24 hour record: percentage of time the esophageal pH was 4 or less for the total 24 hour period, time in the upright and supine positions, the total number of reflux episodes, the number of episodes lasting 5 minutes or longer, and the duration of the longest episode. Patients whose cumulative score exceeded the mean score of control subjects by more than two standard deviations were considered to have an abnormal esophageal exposure to acid gastric juice [4]. The goodness of fit chi-square test was used to assess the normality of the distribution. The Mann=Whitney and Kruskal-Wallis tests were used to compare the differences between the sex, age; height, and weight of the subjects or patients. The chi-square test was used to compare the significance of the consecutive normal percentile values of sphincter pressure, abdominal length, and overall length to discriminate between patients with normal or increased esophageal exposure to acid gastric juice. Results
T h e results of lower esophageal sphincter pressure, a b d o m i n a l length, and overall length in the h e a l t h y subjects are s u m m a r i z e d in T a b l e I. No relationship was observed between these p a r a m e ters and sex, age, height, or weightl T a b l e I also shows the esophageal acid exposure in the h e a l t h y subject expressed as the p e r c e n t a g e of t i m e the p H was below 4 for the total, u p r i g h t and suPine time, the n u m b e r of reflux episodes per 24 hours, how m a n y lasted 5 m i n u t e s or more, a n d the duration of the longest episode. T h e m e a n score of the h e a l t h y volunteers was 5.7 • 4. No relationship was observed between the a m o u n t of esophageal acid exposure and sex, age, height, or weight. A score exceeding 13.31 ( m e a n • 2 s t a n d a r d d e v i a t i o n ) was considered to show a b n o r m a l exposure of the distal esophagus to acid gastric juice. Figure 2 shows the d i s t r i b u t i o n of the lower esophageal sphincter pressure, a b d o m i n a l length, and overall length. T h e first two p a r a m e t e r s did not have a Gaussian distribution, b u t overall length h a d a n o r m a l distribution. Figures 3, 4, a n d 5 show the n o r m o g r a m s constructed f r o m the d a t a for sphinc-
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Zaninotto et al
TABLE I
Normal Esophageal Parameters in 50 Healthy Volunteers Percentile
Mean
SD
Median
Max
Min
2.5
5
95
97.5
Lower Esophageal Sphincter Measurements Pressure (mm Hg) Abdominal length
14.87 2.18
5.14 0.72
13.8 2.2
25.6 5
5.2 0.8
6.1 0.89
8 1.1
. . . . . . . . . . . .
Overall length (cm)
3.65
0.68
3.6
5.5
2.4
2.4
2.6
. . . . . .
(cm)
Esophageal Acid Exposure Total reflux time
137
1.47
1.1
6
0
4.8
5.8
Reflux in upright position ( % ) Reflux in supine position (%) Episodes of reflux (n) Episodes > 5 rain (n) Longest reflux episode (min)
2.35
2.42
1.7
9.3
0
8.4
9.1
0.55
1.02
0
4
0
3.4
3.9
23.87
22.96
20
126
0
51
0.95
1.27
0
5
0
4
6.82
8.25
3.2
46
0
20
(%)
76 4.75 40
SD = standard deviation.
A
12 10
4 2
0
5
10
15 20 mm Hg
25
30
B 15n
1053 84 cm
c
4
151 n
10-
0
1
2
3
4
5
6
cm
Figure 2. Distribution in 50 healthy volunteers of lower esophageal sphincter pressure (A), lower esophageal sphincter abdominal length (B), and lower esophageal sphincter overall length ( C). 106
ter pressure, abdominal length, and overall length based on median and percentile values. The distributions of the sphincter pressure, abdominal length, and overall length for 622 symptomatic patients are shown in Figures 6, 7, and 8. Of this population, 324 (51 percent) had an increased esophageal exposure to gastric juice on 24 hour pH monitoring. Table II shows th e number of patients with normal and abnormal results on the 24 hour pH test stratified according to the percentile values measured innormal subjects for sphincter pressure (Figure 3), abdominal length (Figure 4), and overall length (Figure 5). Only those patients with values below the 50th percentile are listed. Table III shows the statistical ability of these percentile values to discriminate between patients with normal or increased esophageal exposure to acid gastric juice when compared with the immediate preceding percentile or with all preceding percentiles. Statistically significant discrimination occurred below the 2.5 percentile for pressure, the fifth percentile for abdominal length, and the 2.5 percentile for overall length. A sphincter pressure of 6 mm Hg or less, an abdominal length of less than 1 cm, and an overall length of less than 2 cm had an incidence of 79, 80, and 79 percent, respectively, for increased esophageal exposure to acid gastric juice, Sixty percent of the 324 patients with increased esophageal exposure to acid gastric juice had a mechanically incompetent sphincter. F o r t y percent had a sphincter manometric measurement within normal ranges. An isolated low pressure was the most common mechanical defect of the lower esophageal sphincter (Figure 9). The combination of a low pressure and short abdominal length was second, The American Journal of Surgery
The Lower Esophageal Sphincter
mm
cm.
3q
2, ;7
2,
1
ot
1
SD
Percentile
Figure 3. Normogram for lower esophageal sphincter pressure constructed from the normal subjects. To obtain the percentile value for a measured sphincter pressure in the patient population, the value is located on the vertical axis and the horizontal line followed to its intersection with the diagonal (best fit) line. Mean M and + 1 or 2 standard deviations (SD) of the normal subjects is shown on the left.
and an isolated short abdominal length was third. Table IV shows the probability of increased esophageal exposure to acid gastric juice in patients with an isolated or combined mechanical defect of their sphincter. Comments Previous studies have shown that the resistance to gastroesophageal reflux provided by the cardia is dependent on the integrated effect of the distal esophageal sphincter pressure, the length of the sphincter exposed to the positive pressure environment of the abdomen, and its overall length. The distribution of these manometric parameters and the level of esophageal exposure to gastric juice permitted by their integrated function was measured in 50 healthy subjects. There was no relatiom ship between the values obtained and the subjects' sex, age, height, or weight. Normograms were constructed based on median Volume 155, January 1988
SD
Percentile
Figure 4. Normogram f o r the abdominal length of Iowe r esophageal sphincter constructed from the normal subjects. To obtain the percentile value for a measured abdominal length in the patient population, the value is located on the vertical axis and the horizontal line followed to its intersection with the diagonal (best fit) line. Mean (f~f) and • 1 or 2 standard deviations ( SD) for the normal subjects is shown on the left.
and percentile values to evaluate the measurements from symptomatic patients. By this method, a mechanically incompetent sphincter was identified by one or more of the following: an average distal esophageal sphincter pressure below the 2.5 percentile of normal subjects (6 mm Hg or less), an average sphincter length exposed to the positive pressure environment of the abdomen below the fifth percentile (less than 1 cm), and an average overall sphincter length below the 2.5 percentile (less than 2 cm). A low value in one of these components could be compensated for by a higher value in the others, but a low value in all three inevitably led to abnormal esophageal exposure to gastric juice (Table IV). The most common mechanical cause of incompetency was an inadequate distal esophageal sphincter pressure, but the efficiency of a sphincter with normal pressure can be nullified by an inadequate abdominal length or an abnormally short overall 107
Zaninotto et al
m.
6
i!
80Jz'slgs19751>97sl 70 80
5
60
3pulation
40
5
~
20
mm Hg
4 Normal 24 hour pH monitoring Abnormal 24 hour pH monitoring
Figure 6. Distribution of lower esophageal sphincter pressure in 622 symptomatic patients. Seventy-nine percent of the patients with a pressure of 6 mm Hg or less (shaded area)had an abnormal esophageal exposure to acid gastric juice.
18o
~////~ '-'........ ~,ngth Below the 2.5 of Normal Population
1 4 0 ~ n 100
50 40 30 20 10 7,5 5 2.5 <2.5
SD
Percentile
Figure 5. Normogram for the overall length of lower esophageal sphincter constructed from the normal subjects. To obtain the Percentile value for a measured overall length in the patient population, the value is located on the vertical axis and the horizontal line followed to its intersection with the diagonal (best fit) line. Mean ( M) and • 1 Or 2 standard deviations ( SD) for the normal subjects is shown on the left.
180 gth Belowthe 5 ~rmal Population
140 100 60 20 0
1
2
3
4
5
6
7 cm
[ZE] Normal 24 hour pH monitoring I A b n o r m a l 24 hour pH monitoring Figure 7. Distribution of the abdominal length of the lower esophageal sphincter in 622 patients. EightY percent of patients with an abdominal length of less than I cm (shaded area) had an abnormal esophageal exposure to acid gastric juice.
length. In practical terms, this means that patients with a low distal esophageal sphincter pressure, or those with a normal pressure but a short abdominal length, are unable to prevent reflux caused by fluclOS
0
1
I
Normal 24 hour pH monitoring Abnormal 24 hour pH monitoring
2
3
4
5
6
7 cm
Figure 8. Distribution of the overall length of the lower esophageal sphincter in 622 patients. Seventy-nine percent of patients with an overall length of less than 2 cm (shaded area) had an abnormal esophageal exposure to acid gastric juice.
tuations of intraabdominal pressure that occur with daily activities and changes in body position [5], Similarly, patients w i t h low distal esophageal sphincter pressure, or those with a normal pressure but a short overall length, are unable to prevent reflux caused by independent increases in intragastric pressure above the intraabdominal pressure present. We have shown in this situation that reflux occurs whenever the ratio of the distal esophageal sphincter to intragastric pressure is less than that necessary to provide competency for the overall length of sphincter present [1]. Thus, patients who have a short overall sphincter length on a resting esophageal motility study, despite a normal distal esophageal sphincter pressure, are at a disadvantage in protecting against reflux caused by increases in intragastric pressure. Patients who have a short overall sphincter length on a resting esophageal motility study are also less able to protect against reflux caused by progressive gastric dilatation [1]. This is due to the further shortening of the sphincter with gastric dilatation, similar to the shortening The AmericanJournalof Surgery
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TABLE II
Patients With Normal and Abnormal Esophageal Acid Exposure* Pressure
Percentiles
+ 24 h pH
40 30
Abdominal Length -- 24 h pH
-I- 24 h pH
- 24 h pH
27 4
'i;
'7
21 9
Overall Length -t- 24 h pH
-- 24 h pH
31
44
26
23
18
86
75
"4"7'
10 5
35 26
40 41
1 144
0 50
20 12
16 14
52
31
50
13
2.6
145
>2.5
.
38
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
* Patients stratified according to percentiles measured in normal subjects for sphincter pressure, abdominal sphincter length, and overall sphincter length. Only patients whose values were in the 40th percentile or lower are listed. -I- = abnormal 24 hour pH test; - = normal 24 hour pH test.
TABLE III
Data Points to Differentiating Mechanically Competent From Incompetent Sphincters in 622 Symptomatic Patients"
Percentile
Pressure
40 30 20 10 5 2.5
0.63 0.61 0.81 0.88 0.24 0.016
Abdominal Length
Overall Length
0.97 0.97 0.81 0.06 0.006
0.525 0.47 0.76 0.79 0.20 0.04
* Data represented as p values between percentiles.
of the neck of a balloon on inflation. We have shown that reflux occurs in this situation when the overall length decreases below that necessary for the sphincter pressure present to maintain competency
[1].
The observations in this study emphasize that sphincter pressure is not a pressure exerted at a single point, as currently measured by esophageal manometry, but rather an aggregation of pressures exerted over the total length and circumference of the sphincter. Computerized axial manometry is a new method proposed by Bombeck et al [6] to measure this three-dimensional pressure effect. Using this technique, they were able to clearly separate patients whose sphincter efficiency was sufficient to respond to medical therapy from those who required an antireflux procedure to restore sphincter competency. This technology may surpass our current manometric methods for evaluating the mechanical efficiency of the sphincter. From our experience, 24 hour esophageal pH monitoring and esophageal manometry have an important role in selecting patients with gastroesophageal reflux disease for surgical therapy. An abnormal 24 hour pH study confirms an increase in esophageal exposure to acid gastric juice. Symptoms are not a reliable guide to this conclusion, as shown by the studies in the 622 symptomatic pa-
Volume 155, January 1988
~Pressure (P) ......
; Abdomin; Length (A 13.8% ', OL and AL ~ Overall Length (C 6.60/0
12.2% m d AL .6% P and AL 19.40/0
P and OL lO/o Figure 9. Specific manometric abnormalities in 196 patients with increased esophageal exposure to acid gastric juice and abnormal resulfs on sphincter manometry.
TABLE IV
Probability of Reflux in Patients With Abnormal Sphincter Manometric Results
Sphincter Manometric Abnormality Pressure ( < 6 mm Hg) Abdominal length (< 1 cm) Overall length (<2 cm) Overall & abdominal length Pressure & overall length Pressure & abdominal length Pressure & overall & abdominal lengths Total
Abnormal 24 h pH Score Total
n
%
111 39 17 17 3 43 26
81 27 13 11 2 38 24
73 69 76 65 67 88 92
256
196
77
tients, 51 percent of whom did not have increased esophageal acid exposure (Figures 6, 7, and 8). In patients who have abnormal results on a 24 hour pH test, esophageal manometry is useful in identifying those with a mechanically defective sphincter. The incidence of this finding in our patient population was 60 percent. The 40 percent whose sphincter
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Zaninotto et al
manometric measurements were within the normal range either had lowvalues which approached the level identified with a mechanically defective sphincter or had increased esophageal acid exposure due to pathologic conditions of the stomach or esophageal body. Medical treatment of gastroesophageal reflux disease is directed at changing the pH of the refluxed gastric juice [7]. This results in improvement of the patient's symptoms, but does not correct the incompetency of the sphincter in those who have a mechanical defect I8,9]. Consequently, patients who have a mechanically defective sphincter fail to respond to medical therapy or become drug dependent to control their symptoms and have a high incidence of complications [10,11]. These patients should undergo an antireflux procedure to restore mechanical competency to the sphincter before further damage of existing esophageal function occurs from persistent reflux. We have shown that the Nissen fundoplication procedure can correct these manometric abnormalities and restore normal physiologic characteristics to a mechanically incompetent sphincter with a success rate of 91 percent over a 10 year period [12]. Summary
The ability of the lower esophageal sphincter to protect the esophageal mucosa from exposure to gastric juice depends on its resting pressure, length exposed to abdominal pressure, and overa|l length. Mechanical incompetency of the sphincter can occur when one or more of these components fail. The purpose of this study was to measure manometrical]y the normal percentile values for these components, and to identify the point differentiating a mechanically competent from an incompetent sphincter. The results show that a mechanically incompetent sphincter can be identified by a sphincter pressure below the 2.5 percentile, an abdominal length below the fifth percentile, and an overall length below the 2.5 percentile of normal values. Sixty percent of the patients with documented increased esophageal exposure to acid gastric juice had a mechanically incompetent sphincter. References
t. Bonavina L, Evanders A, DeMeester TR, et al. Length of the distal esophageal sphincter and competency of the cardia. Am J Surg 1986; 15: 25-34. 2. Arndorfer RC, Stef JJ, Dodds WJ, Linehan JH, Hogan WJ. Improved infusion system for intraesophageal manometry. Gastroenterology 1977; 73: 23-7. 3. Winans CH. Manometric asymmetry of the lower esophageal high pressure zone. Dig Dis Sci 1977; 22: 348-54. 4. Johnson LF, DeMeester TR. Development of the 24 hour intraesophageal pH monitoring composite score system. J Clin Gastroenterol 1986; 8: 52-8. 5. DeMeester TR, Wernly JA, Bryant GH, Little AG, Skinner DB. A clinical and in vitro analysis of determinants of gastro-
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6.
7. 8.
9. 10.
11. 12.
esophageal competence. A study of the principles of antireflux surgery. Am J Surg 1979; 137: 39-46. Bombeck CT, Vas O, DeSalvo J, Donahue PE, Nyhus LM. Computerized axial rnanometry of the esophagus: a new method for the assessment of antireflux operation. Ann Surg 1987; 206: 465-72. Behar J, Brand DL, Brown F, et al. Cimetidine in the treatment of symptomatic gastroesophageal reflux. A double-blind controlled trial. Gastroenterology 1978; 74: 441-8. Sonnenberg A, Lepsien A, M011er-Lissner SA, Koelz HR, Siewert R, Blum AL. When is esophagitis healed? Esophageal endoscopy, histology and function before and after cimetidine treatment. Dig Dis Sci 1982; 27: 297-302. Lieberman Miller DA, Keefe EB. Treatment of severe reflux esophagitis with cimetidine and metoclopramide. Ann Intern Med 1986; 104: 21-6. Behar J, Sheahan DG, Biancani P, Spiro M, Stover EH. Medical and surgical management of reflux esophagitis. A 38month report on a prospective clinical trial. New Engl J Med 1975; 293: 263-8. lascone C, DeMeester TR, Little AG, Skinner DB. Barrett's esophagus: functional assessment, proposed pathogenesis, and surgical therapy. Arch Surg 1963; 118: 543-9. DeMeester TR, Bonavina L, Albertucci M. Nissen fundoplication for gastroesophageal reflux disease. Evaluation of primary repair in 100 consecutive patients. Ann Surg 1986; 204: 9-20.
Discuss|On
George F. Gowen (Philadelphia, PA): Dr. DeMeester, this study is the culmination of about 10 years of your work in developing the 24 hour pH measuring device. Did you find in your patients with incompetence that there was endoscopic or histologic evidence of esophagitis? In addition, 40 percent of your patients were proved to have a competent lower esophageal sphincter. What was the nature of the disease that would produce these symptoms? James Maher (Iowa City, IA): Dr. DeMeester, I notice that a few of the control patients showed values that, according to your criteria, defined an incompetent lower esophageal sphincter. Did those patients demonstrate reflux on the 24 hour pH studies? If not, it would be interesting to follow that group serially to see whether reflux develops over a longer period. Conversely, did any of the control subjects show abnormal acid exposure as defined by the pH studies, and yet demonstrate normal sphincter mechanics? Finally, I have a question regarding the 40 percent of the population who had normal sphincter mechanics but also reflux, as defined by the pH studies. Your study suggests that these might be secondary to esophageal causes or gastric causes. What was the pattern of reflux in these patients? Did the), have an increased number of episodes, increased supine reflux, upright reflux, or were the episodes more prolonged, which might suggest defective acid clearance? Isn't it even perhaps possible that these patients might have a defect in their gastric sling fibers that Bombeck and his group have described?
Edward R. Woodward (Gainesville, FL): Dr. DeMeester, your study certainly shows beautiful correlation between actual measurements of reflux and the characteristics of the lower esophageal sphincter. I join the other
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commenters in asking about that 40 percent who had reflux despite what appeared to be a normal sphincter structure. Do you think this method may have use in patient selection? If so, how do you suppose it might be used? I reemphasize the importance of manometry in all patients for whom surgery to correct gastroesophageal reflux is proposed. Only by doing this can you note the patient who has early manifestations of a motility disorder, some of which will present primarily with gastroesophageal reflux, Even more importantly, the early symptoms of a motility disorder may be very confusing, and it is not useful to perform a Nissen fundoplication in a patient who has early achalasia or early diffuse spasm of the esophagus. Mervyn Deitel (Toronto, Ontario, Canada) : Dr. DeMeester, your conclusion stated that the manometric characteristics of the lower esophageal sphincter were constant regardless of age, sex, height, and weight. It is the last item that I question. We found subnormal lower esophageal sphincter pressures in 27 of 55 morbidly obese patients (weighing more than 45 kg), all of whom were older than 35 lint Surg 1987; 72:1-3l. Therefore, what was your standard of obesity? Paul H. J o r d a n (Houston, TX) : I agree with Dr. Woodward that the study certainly represents a lot of work on the part of the author. Dr. DeMeester, I presume by an incompetent sphincter you mean that there is reflux. Since you are also the master of pH monitoring, which also identifies the patient who has reflux, how does this new information assist in the management of your patients? Tom R. DeMeester (closing): We believe that antireflux surgery is a mechanical therapeutic approach to the problem of gastroesophageal reflux. Consequently, there must be a mechanical defect in the sphincter if surgical therapy is indicated. We believe that patients who have a mechanical defect are either unable to respond to medical therapy or if they do, become drug dependent and run the risk of complications of the disease while remaining relatively free of heartburn. Consequently, patients who have a mechanically defective sphincter are candidates for operative therapy if effective control of the disease is going to be achieved. If a patient has documented gastroesophageal reflux by 24 hour pH monitoring but has a mechanically normal sphincter, we search for other causes of reflux, which I will mention in a moment. Dr. Gowen, esophagitis is a complication of reflux disease. We are not exactly sure what causes it, but it probably is related to the constituents of the refluxate. Most patients who have a mechanically defective sphincter will
Volume 155, January 1988
also have esophagitis, but not all. Those who do not have esophagitis have persistent symptoms which are difficult to control with medical therapy. The existence of the latter suggests that the deterioration of the sphincter is the initial event and esophagitis is a secondary event. Reflux in patients who have a manometrically competent sphincter is more likely due to gastric pathologic problems such as increased gastric pressure due to a previous vagotomy, outlet obstruction, gastric dilatation, which is not the same as increased gastric pressure and persistent gastric reservoir due to delayed gastric emptying. The most common gastric abnormality that predisposed to reflux is increased gastric acid secretion. These patients have very concentrated physiological reflux. Another cause for increased esophageal exposure to gastric juice in the presence of a normal sphincter is esophageal or pharyngeal abnormalities, such as a decrease in saliva production, esophageal motility disorders, and structural abnormality of the esophagus. An example of the latter is a hiatal hernia, which affects the esophageal clearance of physiologic reflux episodes. A mechanical approach to therapy with antireflux surgery in such patients with a normal sphincter may not be helpful and may produce more problems than it solves. Dr. Maher, none of the normal subjects had increased esophageal exposure to gastric juice because their 24 hour pH monitoring results were used to define normal esophageal acid exposure. In other words, we applied the 24 hour pH score measured in the normal subjects to the symptomatic patient population. Your point, however, is a good one. Do normal subjects with a very low sphincter pressure have increased esophageal acid exposure? The answer is no, and the reason is that other factors in the sphincter can compensate, such as an excessively long sphincter or an excessively long abdominal length. Dr. Deitel, your comment about weight is important. Of course, our normal population excludes people with morbid obesity. We have been taught over the years that morbid obesity is a disease and not a representative portion of the normal population. The weight of normal subjects was within the normal range of the published dietary standards of our country. I suspect that a morbidly obese patient who has a normal 24 hour pH monitoring test would have a sphincter pressure within normal range. I do not know of any data on the subject. It would be an interesting investigation. In summary, I liken the distal esophageal sphincter pressure to the pulse. The pulse is of little help when it is between 70 and 150 mm Hg, but when the pulse decreases to 30 mm Hg, you know something is wrong. Similarly, when the sphincter pressure is below the 2.5 percentile of normal or 6 mm Hg, you know something is wrong. The same holds for a short abdominal and overall sphincter length.
111
T h e function of the lower esophageal sphincter is to protect the esophageal mucosa from excessive exposure to gastric juice. Clinical and in vitro studies have shown t h a t the sphincter's ability to perform this function is d e p e n d e n t on the resistance it imposes to the flow of gastric juice from an environm e n t above atmospheric pressure, the stomach, into an e n v i r o n m e n t below atmospheric pressure, the esophagus. This resistance is due to the integrated mechanical effect of sphincter pressure, overall length and the length exposed to the positive envir o n m e n t a l pressure of the a b d o m e n [1]. Each of these components can be measured by esophageal m a n o m e t r y . F r o m a clinical perspective, mechanical incompetency of the sphincter occurs when o n e or more of these components fail. T h e purpose of this s t u d y was to d e t e r m i n e the normal percentile values for these c o m p o n e n t s and identify the level differentiating a mechanically c o m p e t e n t sphincter f r o m an i n c o m p e t e n t sphincter. T o accomplish this, esophageal m a n o m e t r y was used to measure these sphincter components in normal subjects and a population of patients with s y m p t o m s suggestive of gastroesophageal reflux. T h e latter were divided into those with normal and abnormal esophageal exposure to acid gastric juice based on 24 hour esophageal p H monitoring and t h e n stratified on t h e basis of their m a n o m e t r i c m e a s u r e m e n t s according to the percentile values obtained from the normal subjects. T h e percentile at which the incidence of reflux statistically increased identified the m a n o m e t r i c values for sphincter pressure, abdominal length, and overall length t h a t characterize a mechanically i n c o m p e t e n t sphincter.
From the Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska. Supportedin part by Health Future Foundation, Omaha, Nebraska. Requests for reprints should be addressed to Tom R. DeMeester, ME), Department of Surgery, Creighton University School of Medicine, 601 North 30th Street, Omaha, Nebraska 68105. Presented at the 28th Annual Meeting of the Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 12 and 13, 1987.
104
Patients and Methods The normal population consisted of 50 volunteers who did not have a history of foregut symptoms; upper gastrointestinal disease; or previous esophageal, gastric, duodenal, or biliary surgery. All showed normal results on upper gastrointestinal roentgenographic barium studies, esophageal manometry, and 24 hour esophageal pH monitoring according to previously published standards [4]. There were 19 men and 31 women with a mean age of 35.8 4- 10.3 years (median 33 years, range 23 to 71 years), and a mean body weight of 70.3 + 14.7 kg (median 68 kg, range 47.6 to 131 kg). Each subject signed an informed consent form and all studies were performed at Creighton University Surgical Gastrointestinal Diagnostic and Research Center. The patient population consisted of 622 patients with foregut symptoms who were referred for evaluation over a 10 year period between 1977 and 1987; 430 to the University of Chicago and 192 to Creighton University. Patients who were under the age of 15 or who had undergone previous esophageal or gastric surgery were not included. There were 295 men and 327 women with a mean age of 47.6 4- 19.6 years (median 50 years, range 15 to 82 years). All underwent esophageal manometry and 24 hour esophageal pH monitoring at one of the institutions. Manometry was performed using a single catheter assembly consisting of five fluid-filled, perfused polyvinyl tubes bonded together with five 0.8 mm lateral openings placed 5 cm apart and radially oriented 120 degrees from each other. The recording catheter was continuously perfused with distilled water by way of a low-compliance, pneumohydraulic capillary infusion pump (Arndorfer Medical Specialties, Greendale, WI) at a rate of 0.5 ml/ rain [2I. Each tube was connected to an external pressure transducer (model P2306, Statham transducer, Gould, Cleveland, OH) positioned at the midaxillary level. Before each test, the pressure transducers were calibrated using a mercury-filled manometer so that a change in pressure of 1 mm Hg corresponded to 0.5 mm on the recording paper. The pressure wave forms generated were printed by a Gould ES1000 16 channel recorder on paper running at a velocity of 5 mm/s. A belt pneumograph
The American Journal of Surgery
The Lower Esophageal Sphincter
(Hewlett-Packard) was positioned around the chest to record respiratory excursions. A piezoelectric transducer was taped on the neck at the level of the cricoid cartilage to record pharyngeal swallows. Manometry was performed in the fasted state and all medications were discontinued 24 hours before the test. The subject was placed in the supine position and encouraged to relax. The recording catheter was passed through an anesthetized nostril into the stomach, and withdrawn at 1 cm increments every 20 seconds back into the esophagus. The three manometric characteristics of the distal esophageal sphincter measured were sphincter pressure, abdominal length, and overall length (Figure 1). The end respiratory gastric baseline pressure was used as a zero reference for pressure measurement. A persistent rise in pressure exceeding 2 mm Hg above the gastric baseline marked the distal border of the sphincter. The proximal border was marked by the point where sphincter pressure dropped to end inspiratory esophageal baseline pressure. Five measurements of the distance between these two points were averaged and represented the overall length of the sphincter. The point at which the end inspiratory pressure changed from a positive to a negative deflection represented the respiratory inversion point. Five measurements of the distance between the respiratory inversion point and the distal border of the sphincter, that is, the length of the pressure wave that reflected positive excursions with respiration, were averaged and represented the abdominal length of the sphincter. The amplitude of the sphincter was measured as the difference (in mm Hg) between the gastric baseline and the pressure at the respiratory inversion point during the middle of the respiratory cycle. Five measurements of sphincter pressure were obtained and averaged in order to obviate the variation of pressures at each orifice due to the radial asymmetry of the sphincter [3]. Esophageal pH monitoring was performed using a glass electrode and a portable solid state monitor which sampled and stored esophageal pH at 6 second intervals. The probes were calibrated in a standard buffer solution at a pH of 7 and a pH of I before and after monitoring. The pH probe was passed transnasally and positioned 5 cm above the upper border of the distal esophageal sphincter measured by manometry. The patient or volunteer was sent home and instructed to remain in the upright or sitting position until he or she retired for the evening, to avoid strenuous exertion, and to follow a diet restricted to three meals and composed of food with a pH between 5 and 7. Only water was permitted between meals. A diary was kept of food and fluid intake, symptoms experienced during the monitored period, the time a supine position was assumed in preparation for sleep, and the time of rising in the morning. At the end of the test the stored data were transferred to an IBM personal computer and analyzed using a commercial software program (Gastrosoft| Dallas, TX). Acid reflux was defined as whenever the pH in the esophagus dropped to 4 or less. The amount of esophageal
Volume 155, January 1988
Overall Length r
-~
Gastric Base Line Pressure 4'3 -
~ ~ I1, ,~/l/[lll/~ I ~ , . . "
4~2 1() Sec
4'1
40
~9 'ff ~VVV,!/vv~./ I 38 3'70m RIP j Esophageal Abdominal Length Base Line Pressure
Figure 1. A sample manometric measurement of the lower esophageal sphincter. RIP = respiratory inversion point,
acid exposure was scored using a previously published mathematical formula based on the mean value and standard deviation for six components of the 24 hour record: percentage of time the esophageal pH was 4 or less for the total 24 hour period, time in the upright and supine positions, the total number of reflux episodes, the number of episodes lasting 5 minutes or longer, and the duration of the longest episode. Patients whose cumulative score exceeded the mean score of control subjects by more than two standard deviations were considered to have an abnormal esophageal exposure to acid gastric juice [4]. The goodness of fit chi-square test was used to assess the normality of the distribution. The Mann=Whitney and Kruskal-Wallis tests were used to compare the differences between the sex, age; height, and weight of the subjects or patients. The chi-square test was used to compare the significance of the consecutive normal percentile values of sphincter pressure, abdominal length, and overall length to discriminate between patients with normal or increased esophageal exposure to acid gastric juice. Results
T h e results of lower esophageal sphincter pressure, a b d o m i n a l length, and overall length in the h e a l t h y subjects are s u m m a r i z e d in T a b l e I. No relationship was observed between these p a r a m e ters and sex, age, height, or weightl T a b l e I also shows the esophageal acid exposure in the h e a l t h y subject expressed as the p e r c e n t a g e of t i m e the p H was below 4 for the total, u p r i g h t and suPine time, the n u m b e r of reflux episodes per 24 hours, how m a n y lasted 5 m i n u t e s or more, a n d the duration of the longest episode. T h e m e a n score of the h e a l t h y volunteers was 5.7 • 4. No relationship was observed between the a m o u n t of esophageal acid exposure and sex, age, height, or weight. A score exceeding 13.31 ( m e a n • 2 s t a n d a r d d e v i a t i o n ) was considered to show a b n o r m a l exposure of the distal esophagus to acid gastric juice. Figure 2 shows the d i s t r i b u t i o n of the lower esophageal sphincter pressure, a b d o m i n a l length, and overall length. T h e first two p a r a m e t e r s did not have a Gaussian distribution, b u t overall length h a d a n o r m a l distribution. Figures 3, 4, a n d 5 show the n o r m o g r a m s constructed f r o m the d a t a for sphinc-
105
Zaninotto et al
TABLE I
Normal Esophageal Parameters in 50 Healthy Volunteers Percentile
Mean
SD
Median
Max
Min
2.5
5
95
97.5
Lower Esophageal Sphincter Measurements Pressure (mm Hg) Abdominal length
14.87 2.18
5.14 0.72
13.8 2.2
25.6 5
5.2 0.8
6.1 0.89
8 1.1
. . . . . . . . . . . .
Overall length (cm)
3.65
0.68
3.6
5.5
2.4
2.4
2.6
. . . . . .
(cm)
Esophageal Acid Exposure Total reflux time
137
1.47
1.1
6
0
4.8
5.8
Reflux in upright position ( % ) Reflux in supine position (%) Episodes of reflux (n) Episodes > 5 rain (n) Longest reflux episode (min)
2.35
2.42
1.7
9.3
0
8.4
9.1
0.55
1.02
0
4
0
3.4
3.9
23.87
22.96
20
126
0
51
0.95
1.27
0
5
0
4
6.82
8.25
3.2
46
0
20
(%)
76 4.75 40
SD = standard deviation.
A
12 10
4 2
0
5
10
15 20 mm Hg
25
30
B 15n
1053 84 cm
c
4
151 n
10-
0
1
2
3
4
5
6
cm
Figure 2. Distribution in 50 healthy volunteers of lower esophageal sphincter pressure (A), lower esophageal sphincter abdominal length (B), and lower esophageal sphincter overall length ( C). 106
ter pressure, abdominal length, and overall length based on median and percentile values. The distributions of the sphincter pressure, abdominal length, and overall length for 622 symptomatic patients are shown in Figures 6, 7, and 8. Of this population, 324 (51 percent) had an increased esophageal exposure to gastric juice on 24 hour pH monitoring. Table II shows th e number of patients with normal and abnormal results on the 24 hour pH test stratified according to the percentile values measured innormal subjects for sphincter pressure (Figure 3), abdominal length (Figure 4), and overall length (Figure 5). Only those patients with values below the 50th percentile are listed. Table III shows the statistical ability of these percentile values to discriminate between patients with normal or increased esophageal exposure to acid gastric juice when compared with the immediate preceding percentile or with all preceding percentiles. Statistically significant discrimination occurred below the 2.5 percentile for pressure, the fifth percentile for abdominal length, and the 2.5 percentile for overall length. A sphincter pressure of 6 mm Hg or less, an abdominal length of less than 1 cm, and an overall length of less than 2 cm had an incidence of 79, 80, and 79 percent, respectively, for increased esophageal exposure to acid gastric juice, Sixty percent of the 324 patients with increased esophageal exposure to acid gastric juice had a mechanically incompetent sphincter. F o r t y percent had a sphincter manometric measurement within normal ranges. An isolated low pressure was the most common mechanical defect of the lower esophageal sphincter (Figure 9). The combination of a low pressure and short abdominal length was second, The American Journal of Surgery
The Lower Esophageal Sphincter
mm
cm.
3q
2, ;7
2,
1
ot
1
SD
Percentile
Figure 3. Normogram for lower esophageal sphincter pressure constructed from the normal subjects. To obtain the percentile value for a measured sphincter pressure in the patient population, the value is located on the vertical axis and the horizontal line followed to its intersection with the diagonal (best fit) line. Mean M and + 1 or 2 standard deviations (SD) of the normal subjects is shown on the left.
and an isolated short abdominal length was third. Table IV shows the probability of increased esophageal exposure to acid gastric juice in patients with an isolated or combined mechanical defect of their sphincter. Comments Previous studies have shown that the resistance to gastroesophageal reflux provided by the cardia is dependent on the integrated effect of the distal esophageal sphincter pressure, the length of the sphincter exposed to the positive pressure environment of the abdomen, and its overall length. The distribution of these manometric parameters and the level of esophageal exposure to gastric juice permitted by their integrated function was measured in 50 healthy subjects. There was no relatiom ship between the values obtained and the subjects' sex, age, height, or weight. Normograms were constructed based on median Volume 155, January 1988
SD
Percentile
Figure 4. Normogram f o r the abdominal length of Iowe r esophageal sphincter constructed from the normal subjects. To obtain the percentile value for a measured abdominal length in the patient population, the value is located on the vertical axis and the horizontal line followed to its intersection with the diagonal (best fit) line. Mean (f~f) and • 1 or 2 standard deviations ( SD) for the normal subjects is shown on the left.
and percentile values to evaluate the measurements from symptomatic patients. By this method, a mechanically incompetent sphincter was identified by one or more of the following: an average distal esophageal sphincter pressure below the 2.5 percentile of normal subjects (6 mm Hg or less), an average sphincter length exposed to the positive pressure environment of the abdomen below the fifth percentile (less than 1 cm), and an average overall sphincter length below the 2.5 percentile (less than 2 cm). A low value in one of these components could be compensated for by a higher value in the others, but a low value in all three inevitably led to abnormal esophageal exposure to gastric juice (Table IV). The most common mechanical cause of incompetency was an inadequate distal esophageal sphincter pressure, but the efficiency of a sphincter with normal pressure can be nullified by an inadequate abdominal length or an abnormally short overall 107
Zaninotto et al
m.
6
i!
80Jz'slgs19751>97sl 70 80
5
60
3pulation
40
5
~
20
mm Hg
4 Normal 24 hour pH monitoring Abnormal 24 hour pH monitoring
Figure 6. Distribution of lower esophageal sphincter pressure in 622 symptomatic patients. Seventy-nine percent of the patients with a pressure of 6 mm Hg or less (shaded area)had an abnormal esophageal exposure to acid gastric juice.
18o
~////~ '-'........ ~,ngth Below the 2.5 of Normal Population
1 4 0 ~ n 100
50 40 30 20 10 7,5 5 2.5 <2.5
SD
Percentile
Figure 5. Normogram for the overall length of lower esophageal sphincter constructed from the normal subjects. To obtain the Percentile value for a measured overall length in the patient population, the value is located on the vertical axis and the horizontal line followed to its intersection with the diagonal (best fit) line. Mean ( M) and • 1 Or 2 standard deviations ( SD) for the normal subjects is shown on the left.
180 gth Belowthe 5 ~rmal Population
140 100 60 20 0
1
2
3
4
5
6
7 cm
[ZE] Normal 24 hour pH monitoring I A b n o r m a l 24 hour pH monitoring Figure 7. Distribution of the abdominal length of the lower esophageal sphincter in 622 patients. EightY percent of patients with an abdominal length of less than I cm (shaded area) had an abnormal esophageal exposure to acid gastric juice.
length. In practical terms, this means that patients with a low distal esophageal sphincter pressure, or those with a normal pressure but a short abdominal length, are unable to prevent reflux caused by fluclOS
0
1
I
Normal 24 hour pH monitoring Abnormal 24 hour pH monitoring
2
3
4
5
6
7 cm
Figure 8. Distribution of the overall length of the lower esophageal sphincter in 622 patients. Seventy-nine percent of patients with an overall length of less than 2 cm (shaded area) had an abnormal esophageal exposure to acid gastric juice.
tuations of intraabdominal pressure that occur with daily activities and changes in body position [5], Similarly, patients w i t h low distal esophageal sphincter pressure, or those with a normal pressure but a short overall length, are unable to prevent reflux caused by independent increases in intragastric pressure above the intraabdominal pressure present. We have shown in this situation that reflux occurs whenever the ratio of the distal esophageal sphincter to intragastric pressure is less than that necessary to provide competency for the overall length of sphincter present [1]. Thus, patients who have a short overall sphincter length on a resting esophageal motility study, despite a normal distal esophageal sphincter pressure, are at a disadvantage in protecting against reflux caused by increases in intragastric pressure. Patients who have a short overall sphincter length on a resting esophageal motility study are also less able to protect against reflux caused by progressive gastric dilatation [1]. This is due to the further shortening of the sphincter with gastric dilatation, similar to the shortening The AmericanJournalof Surgery
The L o w e r Esophageal Sphincter
TABLE II
Patients With Normal and Abnormal Esophageal Acid Exposure* Pressure
Percentiles
+ 24 h pH
40 30
Abdominal Length -- 24 h pH
-I- 24 h pH
- 24 h pH
27 4
'i;
'7
21 9
Overall Length -t- 24 h pH
-- 24 h pH
31
44
26
23
18
86
75
"4"7'
10 5
35 26
40 41
1 144
0 50
20 12
16 14
52
31
50
13
2.6
145
>2.5
.
38
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
* Patients stratified according to percentiles measured in normal subjects for sphincter pressure, abdominal sphincter length, and overall sphincter length. Only patients whose values were in the 40th percentile or lower are listed. -I- = abnormal 24 hour pH test; - = normal 24 hour pH test.
TABLE III
Data Points to Differentiating Mechanically Competent From Incompetent Sphincters in 622 Symptomatic Patients"
Percentile
Pressure
40 30 20 10 5 2.5
0.63 0.61 0.81 0.88 0.24 0.016
Abdominal Length
Overall Length
0.97 0.97 0.81 0.06 0.006
0.525 0.47 0.76 0.79 0.20 0.04
* Data represented as p values between percentiles.
of the neck of a balloon on inflation. We have shown that reflux occurs in this situation when the overall length decreases below that necessary for the sphincter pressure present to maintain competency
[1].
The observations in this study emphasize that sphincter pressure is not a pressure exerted at a single point, as currently measured by esophageal manometry, but rather an aggregation of pressures exerted over the total length and circumference of the sphincter. Computerized axial manometry is a new method proposed by Bombeck et al [6] to measure this three-dimensional pressure effect. Using this technique, they were able to clearly separate patients whose sphincter efficiency was sufficient to respond to medical therapy from those who required an antireflux procedure to restore sphincter competency. This technology may surpass our current manometric methods for evaluating the mechanical efficiency of the sphincter. From our experience, 24 hour esophageal pH monitoring and esophageal manometry have an important role in selecting patients with gastroesophageal reflux disease for surgical therapy. An abnormal 24 hour pH study confirms an increase in esophageal exposure to acid gastric juice. Symptoms are not a reliable guide to this conclusion, as shown by the studies in the 622 symptomatic pa-
Volume 155, January 1988
~Pressure (P) ......
; Abdomin; Length (A 13.8% ', OL and AL ~ Overall Length (C 6.60/0
12.2% m d AL .6% P and AL 19.40/0
P and OL lO/o Figure 9. Specific manometric abnormalities in 196 patients with increased esophageal exposure to acid gastric juice and abnormal resulfs on sphincter manometry.
TABLE IV
Probability of Reflux in Patients With Abnormal Sphincter Manometric Results
Sphincter Manometric Abnormality Pressure ( < 6 mm Hg) Abdominal length (< 1 cm) Overall length (<2 cm) Overall & abdominal length Pressure & overall length Pressure & abdominal length Pressure & overall & abdominal lengths Total
Abnormal 24 h pH Score Total
n
%
111 39 17 17 3 43 26
81 27 13 11 2 38 24
73 69 76 65 67 88 92
256
196
77
tients, 51 percent of whom did not have increased esophageal acid exposure (Figures 6, 7, and 8). In patients who have abnormal results on a 24 hour pH test, esophageal manometry is useful in identifying those with a mechanically defective sphincter. The incidence of this finding in our patient population was 60 percent. The 40 percent whose sphincter
109
Zaninotto et al
manometric measurements were within the normal range either had lowvalues which approached the level identified with a mechanically defective sphincter or had increased esophageal acid exposure due to pathologic conditions of the stomach or esophageal body. Medical treatment of gastroesophageal reflux disease is directed at changing the pH of the refluxed gastric juice [7]. This results in improvement of the patient's symptoms, but does not correct the incompetency of the sphincter in those who have a mechanical defect I8,9]. Consequently, patients who have a mechanically defective sphincter fail to respond to medical therapy or become drug dependent to control their symptoms and have a high incidence of complications [10,11]. These patients should undergo an antireflux procedure to restore mechanical competency to the sphincter before further damage of existing esophageal function occurs from persistent reflux. We have shown that the Nissen fundoplication procedure can correct these manometric abnormalities and restore normal physiologic characteristics to a mechanically incompetent sphincter with a success rate of 91 percent over a 10 year period [12]. Summary
The ability of the lower esophageal sphincter to protect the esophageal mucosa from exposure to gastric juice depends on its resting pressure, length exposed to abdominal pressure, and overa|l length. Mechanical incompetency of the sphincter can occur when one or more of these components fail. The purpose of this study was to measure manometrical]y the normal percentile values for these components, and to identify the point differentiating a mechanically competent from an incompetent sphincter. The results show that a mechanically incompetent sphincter can be identified by a sphincter pressure below the 2.5 percentile, an abdominal length below the fifth percentile, and an overall length below the 2.5 percentile of normal values. Sixty percent of the patients with documented increased esophageal exposure to acid gastric juice had a mechanically incompetent sphincter. References
t. Bonavina L, Evanders A, DeMeester TR, et al. Length of the distal esophageal sphincter and competency of the cardia. Am J Surg 1986; 15: 25-34. 2. Arndorfer RC, Stef JJ, Dodds WJ, Linehan JH, Hogan WJ. Improved infusion system for intraesophageal manometry. Gastroenterology 1977; 73: 23-7. 3. Winans CH. Manometric asymmetry of the lower esophageal high pressure zone. Dig Dis Sci 1977; 22: 348-54. 4. Johnson LF, DeMeester TR. Development of the 24 hour intraesophageal pH monitoring composite score system. J Clin Gastroenterol 1986; 8: 52-8. 5. DeMeester TR, Wernly JA, Bryant GH, Little AG, Skinner DB. A clinical and in vitro analysis of determinants of gastro-
110
6.
7. 8.
9. 10.
11. 12.
esophageal competence. A study of the principles of antireflux surgery. Am J Surg 1979; 137: 39-46. Bombeck CT, Vas O, DeSalvo J, Donahue PE, Nyhus LM. Computerized axial rnanometry of the esophagus: a new method for the assessment of antireflux operation. Ann Surg 1987; 206: 465-72. Behar J, Brand DL, Brown F, et al. Cimetidine in the treatment of symptomatic gastroesophageal reflux. A double-blind controlled trial. Gastroenterology 1978; 74: 441-8. Sonnenberg A, Lepsien A, M011er-Lissner SA, Koelz HR, Siewert R, Blum AL. When is esophagitis healed? Esophageal endoscopy, histology and function before and after cimetidine treatment. Dig Dis Sci 1982; 27: 297-302. Lieberman Miller DA, Keefe EB. Treatment of severe reflux esophagitis with cimetidine and metoclopramide. Ann Intern Med 1986; 104: 21-6. Behar J, Sheahan DG, Biancani P, Spiro M, Stover EH. Medical and surgical management of reflux esophagitis. A 38month report on a prospective clinical trial. New Engl J Med 1975; 293: 263-8. lascone C, DeMeester TR, Little AG, Skinner DB. Barrett's esophagus: functional assessment, proposed pathogenesis, and surgical therapy. Arch Surg 1963; 118: 543-9. DeMeester TR, Bonavina L, Albertucci M. Nissen fundoplication for gastroesophageal reflux disease. Evaluation of primary repair in 100 consecutive patients. Ann Surg 1986; 204: 9-20.
Discuss|On
George F. Gowen (Philadelphia, PA): Dr. DeMeester, this study is the culmination of about 10 years of your work in developing the 24 hour pH measuring device. Did you find in your patients with incompetence that there was endoscopic or histologic evidence of esophagitis? In addition, 40 percent of your patients were proved to have a competent lower esophageal sphincter. What was the nature of the disease that would produce these symptoms? James Maher (Iowa City, IA): Dr. DeMeester, I notice that a few of the control patients showed values that, according to your criteria, defined an incompetent lower esophageal sphincter. Did those patients demonstrate reflux on the 24 hour pH studies? If not, it would be interesting to follow that group serially to see whether reflux develops over a longer period. Conversely, did any of the control subjects show abnormal acid exposure as defined by the pH studies, and yet demonstrate normal sphincter mechanics? Finally, I have a question regarding the 40 percent of the population who had normal sphincter mechanics but also reflux, as defined by the pH studies. Your study suggests that these might be secondary to esophageal causes or gastric causes. What was the pattern of reflux in these patients? Did the), have an increased number of episodes, increased supine reflux, upright reflux, or were the episodes more prolonged, which might suggest defective acid clearance? Isn't it even perhaps possible that these patients might have a defect in their gastric sling fibers that Bombeck and his group have described?
Edward R. Woodward (Gainesville, FL): Dr. DeMeester, your study certainly shows beautiful correlation between actual measurements of reflux and the characteristics of the lower esophageal sphincter. I join the other
The AmericanJournal of Surgery
The Lower Esophageal Sphincter
commenters in asking about that 40 percent who had reflux despite what appeared to be a normal sphincter structure. Do you think this method may have use in patient selection? If so, how do you suppose it might be used? I reemphasize the importance of manometry in all patients for whom surgery to correct gastroesophageal reflux is proposed. Only by doing this can you note the patient who has early manifestations of a motility disorder, some of which will present primarily with gastroesophageal reflux, Even more importantly, the early symptoms of a motility disorder may be very confusing, and it is not useful to perform a Nissen fundoplication in a patient who has early achalasia or early diffuse spasm of the esophagus. Mervyn Deitel (Toronto, Ontario, Canada) : Dr. DeMeester, your conclusion stated that the manometric characteristics of the lower esophageal sphincter were constant regardless of age, sex, height, and weight. It is the last item that I question. We found subnormal lower esophageal sphincter pressures in 27 of 55 morbidly obese patients (weighing more than 45 kg), all of whom were older than 35 lint Surg 1987; 72:1-3l. Therefore, what was your standard of obesity? Paul H. J o r d a n (Houston, TX) : I agree with Dr. Woodward that the study certainly represents a lot of work on the part of the author. Dr. DeMeester, I presume by an incompetent sphincter you mean that there is reflux. Since you are also the master of pH monitoring, which also identifies the patient who has reflux, how does this new information assist in the management of your patients? Tom R. DeMeester (closing): We believe that antireflux surgery is a mechanical therapeutic approach to the problem of gastroesophageal reflux. Consequently, there must be a mechanical defect in the sphincter if surgical therapy is indicated. We believe that patients who have a mechanical defect are either unable to respond to medical therapy or if they do, become drug dependent and run the risk of complications of the disease while remaining relatively free of heartburn. Consequently, patients who have a mechanically defective sphincter are candidates for operative therapy if effective control of the disease is going to be achieved. If a patient has documented gastroesophageal reflux by 24 hour pH monitoring but has a mechanically normal sphincter, we search for other causes of reflux, which I will mention in a moment. Dr. Gowen, esophagitis is a complication of reflux disease. We are not exactly sure what causes it, but it probably is related to the constituents of the refluxate. Most patients who have a mechanically defective sphincter will
Volume 155, January 1988
also have esophagitis, but not all. Those who do not have esophagitis have persistent symptoms which are difficult to control with medical therapy. The existence of the latter suggests that the deterioration of the sphincter is the initial event and esophagitis is a secondary event. Reflux in patients who have a manometrically competent sphincter is more likely due to gastric pathologic problems such as increased gastric pressure due to a previous vagotomy, outlet obstruction, gastric dilatation, which is not the same as increased gastric pressure and persistent gastric reservoir due to delayed gastric emptying. The most common gastric abnormality that predisposed to reflux is increased gastric acid secretion. These patients have very concentrated physiological reflux. Another cause for increased esophageal exposure to gastric juice in the presence of a normal sphincter is esophageal or pharyngeal abnormalities, such as a decrease in saliva production, esophageal motility disorders, and structural abnormality of the esophagus. An example of the latter is a hiatal hernia, which affects the esophageal clearance of physiologic reflux episodes. A mechanical approach to therapy with antireflux surgery in such patients with a normal sphincter may not be helpful and may produce more problems than it solves. Dr. Maher, none of the normal subjects had increased esophageal exposure to gastric juice because their 24 hour pH monitoring results were used to define normal esophageal acid exposure. In other words, we applied the 24 hour pH score measured in the normal subjects to the symptomatic patient population. Your point, however, is a good one. Do normal subjects with a very low sphincter pressure have increased esophageal acid exposure? The answer is no, and the reason is that other factors in the sphincter can compensate, such as an excessively long sphincter or an excessively long abdominal length. Dr. Deitel, your comment about weight is important. Of course, our normal population excludes people with morbid obesity. We have been taught over the years that morbid obesity is a disease and not a representative portion of the normal population. The weight of normal subjects was within the normal range of the published dietary standards of our country. I suspect that a morbidly obese patient who has a normal 24 hour pH monitoring test would have a sphincter pressure within normal range. I do not know of any data on the subject. It would be an interesting investigation. In summary, I liken the distal esophageal sphincter pressure to the pulse. The pulse is of little help when it is between 70 and 150 mm Hg, but when the pulse decreases to 30 mm Hg, you know something is wrong. Similarly, when the sphincter pressure is below the 2.5 percentile of normal or 6 mm Hg, you know something is wrong. The same holds for a short abdominal and overall sphincter length.
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