Pyloric-Sphincter Studies in Peptic-Ulcer Patients Pylorus in Peptic Ulcer J O R G E E. V A L E N Z U E L A , MD, and C A R L O S D E F I L I P P I , MD
Pyloric pressure was assayed by a manometric procedure in the basal state and after intraduodenal infusion of HCl. 13 control subjects, 11 patients with benign gastric ulcer, 8 with duodenal ulcer, and 2 with coexistent gastric and duodenal ulcers were studied. Mean resting pyloric pressure in gastric-ulcer patients (5.17 + 0.71) mm Hg) was significantly lower than controls (9.40 + 0.85 mm Hg) and did not increase after HCl perfusion into the duodenum. Mean basal pyloric pressure in duodenal-ulcer patients (11.30 +- 1.57 mm Hg) did not differ significantly from controls and increased after intraduodenal perfusion o f HCl to 15.72 +- 2.40 mm Hg. The two patients with coexistent ulcers had manometric patterns similar to gastric-ulcer patients. Decreased pyloric-sphincter pressure in gastric-ulcer patients may be the mechanism responsible for the increased duodeno-gastric reflux observed in these patients.
The p a t h o p h y s i o l o g y o f g a s t r i c and duodenal ulcer is not fully understood, although present knowledge leads one to believe that the pathogenesis is not identical. One hypothesis is that excessive duodeno-gastric reflux, chronic irritation to the gastric m u c o s a , and gastritis are increased in patients with gastric ulcer (1). Duodeno-gastric reflux seems to depend on the c o m p e t e n c e of the pyloric sphincter (2). Efficiency of the pyloric sphincter in the control of reflux m a y be m e a s u r e d by three different methods: m e a s u r e m e n t of bile salts regurgitated into the gastric lumen (3), estimation of reflux radiologically (4), and direct m e a s u r e m e n t of pyloricsphincter pressure with manometric technique (2, 5). We are reporting our findings with this latter procedure in patients with gastric, duodenal, and coexFrom the Department of Experimental Medicine and Medicine, University of Chile School of Medicine, Santiago, Chile. Address for reprint requests: Dr. Jorge E. Valenznela, VA Wadsworth Hospital Center, Building 115, Room 115, Los Angeles, California 90073. Digestive Diseases, Vol. 21, No. 3 (March 1976)
istent gastric and duodenal ulcers. M A T E R I A L AND M E T H O D S The control group consisted of 13 subjects, nine women and four men whose ages ranged from 16 to 60 years (mean 36.8 years) without evidence of organic gastrointestinal disease. The gastric-ulcer group was composed of 11 patients, 7 men and 4 women from 33 to 83 years (mean 46.5 years). Each of them had an active benign gastric ulcer demonstrated by radiology, endoscopy, and cytology, and confirmed by surgery and histology in 4. All ulcers were in the mid-lesser curvature and their secretory studies either in basal state or after augmented-histamine stimulation demonstrated gastric pH below 2.5. The duodenal-ulcer group consisted of 8 patients, 7 men and 1 woman whose ages ranged from 26 to 45 years (mean 35.3 years). Each of them had either an ulcer crater in the duodenal bulb or deformity, and was studied during an episode of pain or after gastrointestinal bleeding. In addition, 2 other patients were studied, 1 woman and 1 man, 42 and 46 years respectively, in whom a duodenal ulcer had been demonstrated and in whom a gastric ulcer of the mid-lesser curvature eventually developed. In both patients the diagnosis was confirmed by surgery. Their gastric secre-
229
VALENZUELA AND DEFILIPPI
40
40
mmHg
HCI 0.1 30 ML
.
,
0
40 .[ mmHg 20 1 DUODENUM
ANTRUM
40 n
10 sec
10 sec 40- I mmHg
A
A
A
A
A
l
A
A
A
A
A
A
1 cm
1 cm
Fig 1. An example of basal pyloric pressure in one control subject is recorded on the left. Pyloric pressure in the same subject 10 min after 0.1 N HCI was infused intraduodenally is recorded on the right. Pressure recorded by proximal-perfused catheter is in the upper line. Withdrawals (1-cm intervals) are indicated by the arrows. Paper speed is shown by the horizontal line.
toiry studies showed that both secreted at the level considered the upper limit of control subjects in our unit, All the subjects were aware of the study and gave full consent. Manometric studies were performed after fasting overnight. Three attached polyvinyl catheters (internal diameter 1.39 mm) with 3 mm side openings separated by 2 cm and distal radioopaque markers were introduced under fluoroscopic control with an image intensifier. Each catheter was continuously perfused with water (24 drops per rain) from bottles positioned 100 cm above the transducers. The catheters were attached to pressure transducers (Statham P23D, Hato Rey, Puerto Rico) and connected to an eight-channel Gilson Polygraph (model M8PM). A fourth catheter with a side opening 10 cm beyond the most distal hole was used for perfusion. The
mmHg
tests were done with the subjects lying in the right-recumbent position. When all the markers and the holes were in the duodenum and stable readings were obtained, the assembly was withdrawn at 1-cm intervals and left in each position for approximately 30 sec. Withdrawal was continued through the duodenum and antrum. The assembly was then reintroduced and 30 ml of 0.1 N HC1 were perfused into the duodenum at 1.1 ml/min through the fourth catheter. The withdrawal procedure was repeated after 10 min. The procedure was continuously monitored under fluoroscopy. Resting-intraduodenal pressure was used as zero reference. Pyloric pressure was measured as the mean of the highest pressure recorded by each catheter and expressed in mm Hg. The Student's t test was used in the statistical analysis of the data (6).
HCI 0.1 N 3 0 ML
10 sec
10sec
401
40- I
mrnHg 40
4O
0
DUODENUM 40_mmHg
ANTRUM 40
DUODENUM
ANTRUM
0
. . . .
A A 1 cm
A
A
A
A
A 1 cm
A
A
&
&
&
Fig 2. An example of pyloric pressure in one patient with gastric ulcer. The basal pressure is recorded on the left, while recordings on the right were obtained 10 rain after 0.1 N HCI was infused intraduodenally. Withdrawals, sensors, and paper speed as indicated in Figure 1.
2 30
Digestive Diseases, Vol. 21, No. 3 (March 1976)
PYLORIC-SPHINCTER STUDIES
TABLE 1. PYLORIC SPHINCTER PRESSURE (MM HG) IN CONTROL SUBJECTS AND PEPTIC-ULCER PATIENTS
Number of subjects
Basal values
Post-HCl values
P values*
13 11 8
9.40 _+ 0.85 5.17 -+ 0.71 11.30 -+ 1.57
19.40 -+ 41.0 4.85 -+ 1.27 15.72 -+ 2.40
< 0.001 > 0.1
2
4.60
4.60
Controls Gastric ulcer Duodenalulcer Duodenal ulcer plus gastric ulcer
*Statistical significance when compared with basal values and after HCI values in controls.
RESULTS Pyloric-sphincter pressure in control subjects was 9.40 • 0.85 mm Hg (mean • SEM) while patients with gastric ulcer had a significantly lower pressure (5.17 _+ 0.71 mm Hg, P < 0.001). Intraduodenal instillation of 0.1 N HCI significantly increased pyloric pressure in controls (19.40 • 1.41 mm Hg, P < 0.001) (Figure 1) in contrast with gastric-ulcer patients who showed no significant changes after HCI (4.85 • 1.27 mm Hg) (Figure 2). Basal pyloric-sphincter pressure in patients with duodenal ulcer was 11.30 • 1.57 mm Hg and increased after instillation of 0.1 N HC1 to 15.72 -+ 2.40 mm Hg. These values were not significantly different from those observed in controls subjects (P > 0.1). The two patients with coexistent gastric and duodenal ulcers had identical basal pressures (4.60 mm Hg) and their pressure was not modified by 0.1 N HCI (Table 1). DISCUSSION Fisher and Cohen used perfused catheters and observed a high-pressure zone with the characteristics of a sphincter at the gastroduodenal junction (2). These observations have been confirmed in our previous studies (5) but are in disagreement with those by Mehta et al (7). The explanation for the different findings among these groups remains unexplained. A relationship between gastric regurgitation of phenol red perfused into the duodenum and pyloricsphincter pressure was observed. Also, endogenous-hormone release by HC1 in the duodenum increased pyloric pressure and decreased reflux (2). More recently, it was demonstrated that patients with gastric ulcer have pyloric-sphincter dysfunction without increase in pyloric pressure after either endogenous release or exogenous secretin and cholecystokinin administration (8). These findings have been confirmed in the present study, and in addition we have observed that basal pyloric sphincter Digestive Diseases, Vol. 21, No. 3 (March 1976)
pressure in gastric-ulcer patients was significantly lower than controls and it did not respond to instillation of 0. l N HC1. These results suggest that there may be pyloric-sphincter incompetence during the basal state as well as after endogenous-hormone release. It may be postulated that increased duodeno-gastric reflux exists in these patients. Increased duodeno-gastric reflux allows irritation of gastric mucosa by bile acids (9). This may be an important factor in the etiology of gastritis that involves primarily the antrum in patients with gastric ulcer (1). It remains to be determined, however, if pyloric-sphincter dysfunction and duodenal reflux are conditions related to the gastritis or if it is merely a result of the ulcer itself. This relationship would be clarified if diverse conditions frequently associated to chronic gastritis modify the behavior of the pyloric sphincter and consequently increase duodenogastric regurgitation. It also remains to be demonstrated if patients with similar gastritis but without gastric ulcer have pyloric dysfunction. In contrast to patients with gastric ulcer, those with duodenal ulcer exhibited no significant differences from controls. These observations suggest that there is no relationship between duodenal ulcer and pyloric-sphincter pressure. Of interest was the observation in the 2 patients with coexistent ulcers that their pyloric-sphincter pressures were decreased and both did not show a response to HC1 instillation into the duodenum. The pyloric incompetence in these two subjects may be related to the pathogenesis of their gastric ulcers. ACKNOWLEDGMENTS The authors are indebted to Miss A. Luisa Eguiguren for her technical assistance and to Dr. Charles E. Pope II for his advice during this work and valuable comments concerning this manuscript. REFERENCES 1. Capper WM: Factors in the pathogenesis of gastric ulcer. A n n R Coil Surg Eng 1:21-25, 1967
231
VALENZUELA AND DEFILIPPI
2. Fisher RS, Cohen S: Physiological characteristics of the human pyloric sphincter. Gastroenterology 64:67-75, 1973 3. Rhodes J, Barnardo DE, Phillips SF, et al: Increased reflux of bile into the stomach in patients with gastric ulcer. Gastroenterology 57:241-252, 1969 4. Capper WM, Airth GR, Kilby JO: A test for pyloric regurgitation. Lancet 2:261-623, 1966 5. Valenzuela JE, Defilippi C, Eguiguren AL, et al: Estudio manometrico del esfinter pilorico. Rev Med Chile 102:841843, 1974
232
6. Snedecor GW, Cochran WC: Statistical methods, Fifth edition. Ames, Iowa State University Press, 1956 7. Mehta SJ, Kaye MD, Showalter JP: Is there a pyloric sphincter? Gastroenterology 66:746, 1974 8. Fisher RS, Cohen S: Pyloric sphincter dysfunction in patients with gastric ulcer. New Eng J Med 288:273-276, 1973 9. Grant R, Grossman MI, Wang KJ, et al: The cytolytic action of some gastrointestinal secretions and enzymes on epithelial cells of gastric and duodenal mucosa. J Cell Comp Physiol 37:137-161, 1951
Digestive Diseases, Vol. 21, No. 3 (March 1976)
Pyloric pressure was assayed by a manometric procedure in the basal state and after intraduodenal infusion of HCl. 13 control subjects, 11 patients with benign gastric ulcer, 8 with duodenal ulcer, and 2 with coexistent gastric and duodenal ulcers were studied. Mean resting pyloric pressure in gastric-ulcer patients (5.17 + 0.71) mm Hg) was significantly lower than controls (9.40 + 0.85 mm Hg) and did not increase after HCl perfusion into the duodenum. Mean basal pyloric pressure in duodenal-ulcer patients (11.30 +- 1.57 mm Hg) did not differ significantly from controls and increased after intraduodenal perfusion o f HCl to 15.72 +- 2.40 mm Hg. The two patients with coexistent ulcers had manometric patterns similar to gastric-ulcer patients. Decreased pyloric-sphincter pressure in gastric-ulcer patients may be the mechanism responsible for the increased duodeno-gastric reflux observed in these patients.
The p a t h o p h y s i o l o g y o f g a s t r i c and duodenal ulcer is not fully understood, although present knowledge leads one to believe that the pathogenesis is not identical. One hypothesis is that excessive duodeno-gastric reflux, chronic irritation to the gastric m u c o s a , and gastritis are increased in patients with gastric ulcer (1). Duodeno-gastric reflux seems to depend on the c o m p e t e n c e of the pyloric sphincter (2). Efficiency of the pyloric sphincter in the control of reflux m a y be m e a s u r e d by three different methods: m e a s u r e m e n t of bile salts regurgitated into the gastric lumen (3), estimation of reflux radiologically (4), and direct m e a s u r e m e n t of pyloricsphincter pressure with manometric technique (2, 5). We are reporting our findings with this latter procedure in patients with gastric, duodenal, and coexFrom the Department of Experimental Medicine and Medicine, University of Chile School of Medicine, Santiago, Chile. Address for reprint requests: Dr. Jorge E. Valenznela, VA Wadsworth Hospital Center, Building 115, Room 115, Los Angeles, California 90073. Digestive Diseases, Vol. 21, No. 3 (March 1976)
istent gastric and duodenal ulcers. M A T E R I A L AND M E T H O D S The control group consisted of 13 subjects, nine women and four men whose ages ranged from 16 to 60 years (mean 36.8 years) without evidence of organic gastrointestinal disease. The gastric-ulcer group was composed of 11 patients, 7 men and 4 women from 33 to 83 years (mean 46.5 years). Each of them had an active benign gastric ulcer demonstrated by radiology, endoscopy, and cytology, and confirmed by surgery and histology in 4. All ulcers were in the mid-lesser curvature and their secretory studies either in basal state or after augmented-histamine stimulation demonstrated gastric pH below 2.5. The duodenal-ulcer group consisted of 8 patients, 7 men and 1 woman whose ages ranged from 26 to 45 years (mean 35.3 years). Each of them had either an ulcer crater in the duodenal bulb or deformity, and was studied during an episode of pain or after gastrointestinal bleeding. In addition, 2 other patients were studied, 1 woman and 1 man, 42 and 46 years respectively, in whom a duodenal ulcer had been demonstrated and in whom a gastric ulcer of the mid-lesser curvature eventually developed. In both patients the diagnosis was confirmed by surgery. Their gastric secre-
229
VALENZUELA AND DEFILIPPI
40
40
mmHg
HCI 0.1 30 ML
.
,
0
40 .[ mmHg 20 1 DUODENUM
ANTRUM
40 n
10 sec
10 sec 40- I mmHg
A
A
A
A
A
l
A
A
A
A
A
A
1 cm
1 cm
Fig 1. An example of basal pyloric pressure in one control subject is recorded on the left. Pyloric pressure in the same subject 10 min after 0.1 N HCI was infused intraduodenally is recorded on the right. Pressure recorded by proximal-perfused catheter is in the upper line. Withdrawals (1-cm intervals) are indicated by the arrows. Paper speed is shown by the horizontal line.
toiry studies showed that both secreted at the level considered the upper limit of control subjects in our unit, All the subjects were aware of the study and gave full consent. Manometric studies were performed after fasting overnight. Three attached polyvinyl catheters (internal diameter 1.39 mm) with 3 mm side openings separated by 2 cm and distal radioopaque markers were introduced under fluoroscopic control with an image intensifier. Each catheter was continuously perfused with water (24 drops per rain) from bottles positioned 100 cm above the transducers. The catheters were attached to pressure transducers (Statham P23D, Hato Rey, Puerto Rico) and connected to an eight-channel Gilson Polygraph (model M8PM). A fourth catheter with a side opening 10 cm beyond the most distal hole was used for perfusion. The
mmHg
tests were done with the subjects lying in the right-recumbent position. When all the markers and the holes were in the duodenum and stable readings were obtained, the assembly was withdrawn at 1-cm intervals and left in each position for approximately 30 sec. Withdrawal was continued through the duodenum and antrum. The assembly was then reintroduced and 30 ml of 0.1 N HC1 were perfused into the duodenum at 1.1 ml/min through the fourth catheter. The withdrawal procedure was repeated after 10 min. The procedure was continuously monitored under fluoroscopy. Resting-intraduodenal pressure was used as zero reference. Pyloric pressure was measured as the mean of the highest pressure recorded by each catheter and expressed in mm Hg. The Student's t test was used in the statistical analysis of the data (6).
HCI 0.1 N 3 0 ML
10 sec
10sec
401
40- I
mrnHg 40
4O
0
DUODENUM 40_mmHg
ANTRUM 40
DUODENUM
ANTRUM
0
. . . .
A A 1 cm
A
A
A
A
A 1 cm
A
A
&
&
&
Fig 2. An example of pyloric pressure in one patient with gastric ulcer. The basal pressure is recorded on the left, while recordings on the right were obtained 10 rain after 0.1 N HCI was infused intraduodenally. Withdrawals, sensors, and paper speed as indicated in Figure 1.
2 30
Digestive Diseases, Vol. 21, No. 3 (March 1976)
PYLORIC-SPHINCTER STUDIES
TABLE 1. PYLORIC SPHINCTER PRESSURE (MM HG) IN CONTROL SUBJECTS AND PEPTIC-ULCER PATIENTS
Number of subjects
Basal values
Post-HCl values
P values*
13 11 8
9.40 _+ 0.85 5.17 -+ 0.71 11.30 -+ 1.57
19.40 -+ 41.0 4.85 -+ 1.27 15.72 -+ 2.40
< 0.001 > 0.1
2
4.60
4.60
Controls Gastric ulcer Duodenalulcer Duodenal ulcer plus gastric ulcer
*Statistical significance when compared with basal values and after HCI values in controls.
RESULTS Pyloric-sphincter pressure in control subjects was 9.40 • 0.85 mm Hg (mean • SEM) while patients with gastric ulcer had a significantly lower pressure (5.17 _+ 0.71 mm Hg, P < 0.001). Intraduodenal instillation of 0.1 N HCI significantly increased pyloric pressure in controls (19.40 • 1.41 mm Hg, P < 0.001) (Figure 1) in contrast with gastric-ulcer patients who showed no significant changes after HCI (4.85 • 1.27 mm Hg) (Figure 2). Basal pyloric-sphincter pressure in patients with duodenal ulcer was 11.30 • 1.57 mm Hg and increased after instillation of 0.1 N HC1 to 15.72 -+ 2.40 mm Hg. These values were not significantly different from those observed in controls subjects (P > 0.1). The two patients with coexistent gastric and duodenal ulcers had identical basal pressures (4.60 mm Hg) and their pressure was not modified by 0.1 N HCI (Table 1). DISCUSSION Fisher and Cohen used perfused catheters and observed a high-pressure zone with the characteristics of a sphincter at the gastroduodenal junction (2). These observations have been confirmed in our previous studies (5) but are in disagreement with those by Mehta et al (7). The explanation for the different findings among these groups remains unexplained. A relationship between gastric regurgitation of phenol red perfused into the duodenum and pyloricsphincter pressure was observed. Also, endogenous-hormone release by HC1 in the duodenum increased pyloric pressure and decreased reflux (2). More recently, it was demonstrated that patients with gastric ulcer have pyloric-sphincter dysfunction without increase in pyloric pressure after either endogenous release or exogenous secretin and cholecystokinin administration (8). These findings have been confirmed in the present study, and in addition we have observed that basal pyloric sphincter Digestive Diseases, Vol. 21, No. 3 (March 1976)
pressure in gastric-ulcer patients was significantly lower than controls and it did not respond to instillation of 0. l N HC1. These results suggest that there may be pyloric-sphincter incompetence during the basal state as well as after endogenous-hormone release. It may be postulated that increased duodeno-gastric reflux exists in these patients. Increased duodeno-gastric reflux allows irritation of gastric mucosa by bile acids (9). This may be an important factor in the etiology of gastritis that involves primarily the antrum in patients with gastric ulcer (1). It remains to be determined, however, if pyloric-sphincter dysfunction and duodenal reflux are conditions related to the gastritis or if it is merely a result of the ulcer itself. This relationship would be clarified if diverse conditions frequently associated to chronic gastritis modify the behavior of the pyloric sphincter and consequently increase duodenogastric regurgitation. It also remains to be demonstrated if patients with similar gastritis but without gastric ulcer have pyloric dysfunction. In contrast to patients with gastric ulcer, those with duodenal ulcer exhibited no significant differences from controls. These observations suggest that there is no relationship between duodenal ulcer and pyloric-sphincter pressure. Of interest was the observation in the 2 patients with coexistent ulcers that their pyloric-sphincter pressures were decreased and both did not show a response to HC1 instillation into the duodenum. The pyloric incompetence in these two subjects may be related to the pathogenesis of their gastric ulcers. ACKNOWLEDGMENTS The authors are indebted to Miss A. Luisa Eguiguren for her technical assistance and to Dr. Charles E. Pope II for his advice during this work and valuable comments concerning this manuscript. REFERENCES 1. Capper WM: Factors in the pathogenesis of gastric ulcer. A n n R Coil Surg Eng 1:21-25, 1967
231
VALENZUELA AND DEFILIPPI
2. Fisher RS, Cohen S: Physiological characteristics of the human pyloric sphincter. Gastroenterology 64:67-75, 1973 3. Rhodes J, Barnardo DE, Phillips SF, et al: Increased reflux of bile into the stomach in patients with gastric ulcer. Gastroenterology 57:241-252, 1969 4. Capper WM, Airth GR, Kilby JO: A test for pyloric regurgitation. Lancet 2:261-623, 1966 5. Valenzuela JE, Defilippi C, Eguiguren AL, et al: Estudio manometrico del esfinter pilorico. Rev Med Chile 102:841843, 1974
232
6. Snedecor GW, Cochran WC: Statistical methods, Fifth edition. Ames, Iowa State University Press, 1956 7. Mehta SJ, Kaye MD, Showalter JP: Is there a pyloric sphincter? Gastroenterology 66:746, 1974 8. Fisher RS, Cohen S: Pyloric sphincter dysfunction in patients with gastric ulcer. New Eng J Med 288:273-276, 1973 9. Grant R, Grossman MI, Wang KJ, et al: The cytolytic action of some gastrointestinal secretions and enzymes on epithelial cells of gastric and duodenal mucosa. J Cell Comp Physiol 37:137-161, 1951
Digestive Diseases, Vol. 21, No. 3 (March 1976)
