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Is esophageal bile reflux associated with alkaline reflux? A 24-hr intraesophageal bili-, pH-, and manometry study in patients with gastroesophageal reflux disease and healthy controls
A120
AGA ABSTRACTS
GASTROENTEROLOGY, VoI. IO8, No. 4
NEUTROPHILACFIVATIONINDUCEDBY H. PYLORIFXTRACT S. Iinuma, N. Yoshida, S. Takenaka, IC Sakamoto, T. Miyajima, Nakamura, T. Takemura, T. Yoshikawa, M. Kondo. First Department of Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602, Japan Gastric mucosal injury associated with H. pylori infecUon is characterized by neutrophil accumulation within the gastric mucosa. Our recent in vitro studies indicated that water extract of tI. pylori induced surface expression of C D l l / C D 1 8 adhesion molecules on neutrophils and promoted neutrophil adherence to endothelial cells. It has been known that there are many kinds of species in H.pylori organism. However, it has been unclear whether there is relationship bet~,een H.pylori strain and degree of inflammation with neutrophil infiltration. Thus, the objective of this study was to determine the effects of water extracts prepared from 6 kinds of strains of H. pylori on neutrophil activation, which is estimated by both expression of adhesion molecules on neutrophils and active oxygen species production from neutrophils. Neutrophils and endothelial cells were isolated from peripheral blood of healthy adults and human umbilical veins, respectively. All extracts of H. pylori from patients with gastric ulcers increased the surface expression of CD1 lb and CD18 on neutrophils, and promoted neutrophll a d h eren ce to endothelial cells. There were positive correlation between the degree of expression of C D l l b or CD18 and ratio of neutrophil adherence. In addition, all water extracts induced superoxlde production from human neutrophils, however, this activity was significantly different among H. pylori strains. These results suggest that there are significant difference in inflammation-promoting activity among H. pylori strains.
• IS ESOPHAGEAL BILE REFLUX ASSOCIATED WITH ALKAUNE REFLUX ? A 24-HR INTRAESOPHAGEALRIM-, PH-, AND MANOMETRYSTUDYIN PATIENTS WITH GASTROESOPHAGEALREFLUXDISEASEAND HEALTHYCONTROLS. W. Inauen B. Loosli, S. Hudimann, F. Halter, W. Schwizer. Depts. of Gastroenterology, University Hospitals of Bern and Zurich, Switzerland. Bile reflux appears to be a major factor in the development of complications in gastroesophageal reflux disease (GERD). Whether alkaline reflux (measured by pH-metry) does reflect bile reflux is still under debate. Since accurate determination of bile reflux is essential for long-term studies, we tested the association between esophageal bile and alkaline reflux in patients with GERD and healthy controls. Methods: Combined 24-hr measurements of intraesophagaal bilirubin concentration, pH, and pressure were performed in 10 patients with endoscopically proven reflux esophagitis and 10 healthy controls. Measurements were performed after a drug free period of at least 1 week. Reflux of bilirubin was monitored 5 cm above the lower esophageal sphincter (LES) using a fiberoptic miniprobe. Bilirubin concentration was calculated based on the difference in the absorption of the refluate at 470 and 565 nm (absorption peak of bilirubin 453 nm). In vitro-expedments with human bile showed a high accuracy of this method for a wide range of bilirubin concentrations. Alkaline and acid reflux was determined with a glass electrode, also located 5 cm above the LES. For identification of the LES and monitoring of intraesophageal pressure, a catheter with 4 microtransducers was used. All parameters were studied for 24 hrs under ambulatory conditions. Bile reflux, alkaline reflux, and acid reflux were analyzed with computerized programs. Results: Patients with GERD had markedly higher values for bile reflux and acid reflux (Table). Alkaline reflux was not different in patients and controls. No correlation was found between bile reflux and alkaline reflux (r=0.183, n=20). Healthy Controls GERD-Patients Bile reflux Alkaline reflux (pH > 7.0) Acidreflux (pH<4.0)
% % %
3.1 (0.2-26.6) 3.7 (1.6-19.6) 1.1 (0.2- 4.6)
27.7 (4.9-69.8)" 0.6 (0-14.1) 13.8(9.6-72.5)*"
Median (range); n=10; *p<0.02, **p<0.001 (Wilcoxon signed rank test). Conclusions: Our results indicate that alkaline reflux does not predict bile reflux. For an accurate determination of bile reflux, the use of specific photometric probes appears mandatory.
RISK FACTORS OF GASTRIC ULCER (GU) RELAF~E. A STUDY ON 626 CONSECUTIVE PATIENTS FOLLOVCED-UP FOR 12 MONTHS• G.LS.U. (Interdisciplinary Stud5" Group for Ulcer study). Italy.
RELATIONSMIP OF UPRIGHT AND SUPINE GASTROESOPtlAGEAL R E l ~ U X T O E N D O S C O P I C A N D M A N O M K r l d C F I N D I N G S . A~rian P. Ireland , Werner Kauer, Geoff W.B. Clark, Jeffrey H. Peters, Cedric G. Brenmer. Tom R. DeMeester. USC Department of Surgery, Los Angeles, CA.
With the aim to disclose risk factors of relapse, we evaluated all GU patients consecutively referred to GISU centers between 1987 and 1991 concluding follow-up studies in either open or double--blind fashion. Exclusion criteria were as follows. 5toni < ulcer > 30ram, concomitant daedcoal ulcer, previous major UGI surgeD:, pregnancy or lactation, predictable low compliance, drug addiction, alcoholism, gastric neoplasms, severe concomitant diseases, healing phase longer than 12 weeks. All patients, with healed GU at the endoscopic control, repeated endoscopy at 3rd, 6th, 12th month and at every' symplomatic relapse lasting more than three days. At least 6 biopsies on ulcer edge or sear were taken at each control to exclude maliguancv. The following parameters were taken into account: treatment carried out, sex, age. height, weight, peptic ulcer family history (PUFH), smoking habit, alcohol intake, ulcer number, ulcer size. timing to obtain healing of active lesion. Statistics: results were evahialed on Per Protocol basis using likelihcod-mtio chi square test and life tables (Mantel-Cox) with BMDP Statistical Software. Results: 626 patients were evaluated; 107 treated with ranitidine 150 mg (R), 77 with sucralfate 2 g (S), 73 with no treatment (NT). 119 ~5th nizatidine 150 mg (N), 95 with placebo (P). 155 with omeprazolo 20 mg each other day (O). O. R, N and S treated patients were proven to havc better clinical outcomes than NT and P (table 1), as well as males and subjects with positive PUFH were both proven to be more prone to relapse (table 2). Table 1. Remission rotes after 12 months/:SE):
There is continuing controversy regarding the relative importance of increased esophageal exposure to acid throughout or isolated to a part of the 24 hour study period. In particular the significance of isolated upright reflux has been questioned. 222 patients with symptoms of gastroesophageal reflux disease were studied with stationary manometxy, 24 hour esophageal pH monitoring and upper gastrointestinal endoscopy to investigate the relationship between patterns of reflux to manometric and endoscopic findings. Increased exposure to acid during both upright and supine periods defined the combined refluxer (N = 102). Upright (5I=27) or supine (N = 5 3 ) refluxers were those patients who had a percentage time < pH 4 during that period alone greater then the upper limit of normal defined from 50 normal volunteers. A defective lower esophageal sphincter was designated by either; overall length < 2 cm, abdominal length < I cm or pressure < 6 ram Hg. Patients were considered to have no injury when there was grade 0-1 esophagitis and to have injury for a higher grade esophagitis. Comparison between prevalence data was with the Chi squared test and between continuous data with the Kruskal-Wallis and Wilcoxon tests. Sigmficance was taken at the p < 0.05 level.
I 86.0a~3.4 R
S
NT
N
P
[
O
79.2--1:4.6 65.7:J:5.6 76.5--1:3.9 52.6:t:5.1 81.9-23.1
<0.PO001
"Fable 2, Remission rates in patients divided accordth~, to sex and PUFH ~±SE): males females [ PUFH +ve] PUIrit-ve ] 70.9"~-2.4 80.4-+-2.4 p=0.0075 [ 76.0"&2.6 [ 87.0"~.9 l p=0.01081
I
Conclusion: omeprazole, H2-bleekers and sucralfate were confirmed to signifieamb reduce GU relapses when compared with both no treatment and placebo. Male sex and positive PUFH must both be taken into account to predict GU relapse.
Sphi~r
H~rml at 16 cm at 21 cm ~ia~ % *(nun Hg) * ( m m H g ) pH<4 *(rain) Combined 70 79 65 52('32-75) 42(19-65) 28(17-46) Upright 66 48 45 64445-96) 44~'2g-74) 15(7.5~27) Supine 54 44 42 65(49-117) 63(4&-ST) 23(13-36) Leimecqumfie ranse m bcacgeta, t ' t ' m " e mem below the cn coidA defective sphincter was equally common in the three groups. Isolated refluxers had a similar prevalence of injury which was significantly lower than that of combined refuxers. Isolated supine refinxers had a significandy lower prevalence of hiatal hernia and had a higher c o n t r i t i o n amplitude in the diqal esophagus compared to combined reflnxers (p=0.01 at 16cm, p = 0 . 0 2 at 2tcm). The d u r a ~ n of the longnst reflux ephuxie was greatex in supine refluxe~ compared to upright refluxefs (p=0.04). Patients with combined reflux have more severe disease than patients with isolated reflux. However up to one half of the patients with isolated reflux have evidence of ~ injury and two thffds have a mechanically defective sphincter. O f intefeat isolated upright refluxess have lower distal esophageal contraction amplitudes than isolated supine refluxers. Given that upright refluxers have a high prevalence of a d ~ v e lower esophageal sphincter and often exhibit significant esophageal injury the reluctance to offer surgery to this group of patients may be unwarranted.
AGA ABSTRACTS
GASTROENTEROLOGY, VoI. IO8, No. 4
NEUTROPHILACFIVATIONINDUCEDBY H. PYLORIFXTRACT S. Iinuma, N. Yoshida, S. Takenaka, IC Sakamoto, T. Miyajima, Nakamura, T. Takemura, T. Yoshikawa, M. Kondo. First Department of Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602, Japan Gastric mucosal injury associated with H. pylori infecUon is characterized by neutrophil accumulation within the gastric mucosa. Our recent in vitro studies indicated that water extract of tI. pylori induced surface expression of C D l l / C D 1 8 adhesion molecules on neutrophils and promoted neutrophil adherence to endothelial cells. It has been known that there are many kinds of species in H.pylori organism. However, it has been unclear whether there is relationship bet~,een H.pylori strain and degree of inflammation with neutrophil infiltration. Thus, the objective of this study was to determine the effects of water extracts prepared from 6 kinds of strains of H. pylori on neutrophil activation, which is estimated by both expression of adhesion molecules on neutrophils and active oxygen species production from neutrophils. Neutrophils and endothelial cells were isolated from peripheral blood of healthy adults and human umbilical veins, respectively. All extracts of H. pylori from patients with gastric ulcers increased the surface expression of CD1 lb and CD18 on neutrophils, and promoted neutrophll a d h eren ce to endothelial cells. There were positive correlation between the degree of expression of C D l l b or CD18 and ratio of neutrophil adherence. In addition, all water extracts induced superoxlde production from human neutrophils, however, this activity was significantly different among H. pylori strains. These results suggest that there are significant difference in inflammation-promoting activity among H. pylori strains.
• IS ESOPHAGEAL BILE REFLUX ASSOCIATED WITH ALKAUNE REFLUX ? A 24-HR INTRAESOPHAGEALRIM-, PH-, AND MANOMETRYSTUDYIN PATIENTS WITH GASTROESOPHAGEALREFLUXDISEASEAND HEALTHYCONTROLS. W. Inauen B. Loosli, S. Hudimann, F. Halter, W. Schwizer. Depts. of Gastroenterology, University Hospitals of Bern and Zurich, Switzerland. Bile reflux appears to be a major factor in the development of complications in gastroesophageal reflux disease (GERD). Whether alkaline reflux (measured by pH-metry) does reflect bile reflux is still under debate. Since accurate determination of bile reflux is essential for long-term studies, we tested the association between esophageal bile and alkaline reflux in patients with GERD and healthy controls. Methods: Combined 24-hr measurements of intraesophagaal bilirubin concentration, pH, and pressure were performed in 10 patients with endoscopically proven reflux esophagitis and 10 healthy controls. Measurements were performed after a drug free period of at least 1 week. Reflux of bilirubin was monitored 5 cm above the lower esophageal sphincter (LES) using a fiberoptic miniprobe. Bilirubin concentration was calculated based on the difference in the absorption of the refluate at 470 and 565 nm (absorption peak of bilirubin 453 nm). In vitro-expedments with human bile showed a high accuracy of this method for a wide range of bilirubin concentrations. Alkaline and acid reflux was determined with a glass electrode, also located 5 cm above the LES. For identification of the LES and monitoring of intraesophageal pressure, a catheter with 4 microtransducers was used. All parameters were studied for 24 hrs under ambulatory conditions. Bile reflux, alkaline reflux, and acid reflux were analyzed with computerized programs. Results: Patients with GERD had markedly higher values for bile reflux and acid reflux (Table). Alkaline reflux was not different in patients and controls. No correlation was found between bile reflux and alkaline reflux (r=0.183, n=20). Healthy Controls GERD-Patients Bile reflux Alkaline reflux (pH > 7.0) Acidreflux (pH<4.0)
% % %
3.1 (0.2-26.6) 3.7 (1.6-19.6) 1.1 (0.2- 4.6)
27.7 (4.9-69.8)" 0.6 (0-14.1) 13.8(9.6-72.5)*"
Median (range); n=10; *p<0.02, **p<0.001 (Wilcoxon signed rank test). Conclusions: Our results indicate that alkaline reflux does not predict bile reflux. For an accurate determination of bile reflux, the use of specific photometric probes appears mandatory.
RISK FACTORS OF GASTRIC ULCER (GU) RELAF~E. A STUDY ON 626 CONSECUTIVE PATIENTS FOLLOVCED-UP FOR 12 MONTHS• G.LS.U. (Interdisciplinary Stud5" Group for Ulcer study). Italy.
RELATIONSMIP OF UPRIGHT AND SUPINE GASTROESOPtlAGEAL R E l ~ U X T O E N D O S C O P I C A N D M A N O M K r l d C F I N D I N G S . A~rian P. Ireland , Werner Kauer, Geoff W.B. Clark, Jeffrey H. Peters, Cedric G. Brenmer. Tom R. DeMeester. USC Department of Surgery, Los Angeles, CA.
With the aim to disclose risk factors of relapse, we evaluated all GU patients consecutively referred to GISU centers between 1987 and 1991 concluding follow-up studies in either open or double--blind fashion. Exclusion criteria were as follows. 5toni < ulcer > 30ram, concomitant daedcoal ulcer, previous major UGI surgeD:, pregnancy or lactation, predictable low compliance, drug addiction, alcoholism, gastric neoplasms, severe concomitant diseases, healing phase longer than 12 weeks. All patients, with healed GU at the endoscopic control, repeated endoscopy at 3rd, 6th, 12th month and at every' symplomatic relapse lasting more than three days. At least 6 biopsies on ulcer edge or sear were taken at each control to exclude maliguancv. The following parameters were taken into account: treatment carried out, sex, age. height, weight, peptic ulcer family history (PUFH), smoking habit, alcohol intake, ulcer number, ulcer size. timing to obtain healing of active lesion. Statistics: results were evahialed on Per Protocol basis using likelihcod-mtio chi square test and life tables (Mantel-Cox) with BMDP Statistical Software. Results: 626 patients were evaluated; 107 treated with ranitidine 150 mg (R), 77 with sucralfate 2 g (S), 73 with no treatment (NT). 119 ~5th nizatidine 150 mg (N), 95 with placebo (P). 155 with omeprazolo 20 mg each other day (O). O. R, N and S treated patients were proven to havc better clinical outcomes than NT and P (table 1), as well as males and subjects with positive PUFH were both proven to be more prone to relapse (table 2). Table 1. Remission rotes after 12 months/:SE):
There is continuing controversy regarding the relative importance of increased esophageal exposure to acid throughout or isolated to a part of the 24 hour study period. In particular the significance of isolated upright reflux has been questioned. 222 patients with symptoms of gastroesophageal reflux disease were studied with stationary manometxy, 24 hour esophageal pH monitoring and upper gastrointestinal endoscopy to investigate the relationship between patterns of reflux to manometric and endoscopic findings. Increased exposure to acid during both upright and supine periods defined the combined refluxer (N = 102). Upright (5I=27) or supine (N = 5 3 ) refluxers were those patients who had a percentage time < pH 4 during that period alone greater then the upper limit of normal defined from 50 normal volunteers. A defective lower esophageal sphincter was designated by either; overall length < 2 cm, abdominal length < I cm or pressure < 6 ram Hg. Patients were considered to have no injury when there was grade 0-1 esophagitis and to have injury for a higher grade esophagitis. Comparison between prevalence data was with the Chi squared test and between continuous data with the Kruskal-Wallis and Wilcoxon tests. Sigmficance was taken at the p < 0.05 level.
I 86.0a~3.4 R
S
NT
N
P
[
O
79.2--1:4.6 65.7:J:5.6 76.5--1:3.9 52.6:t:5.1 81.9-23.1
<0.PO001
"Fable 2, Remission rates in patients divided accordth~, to sex and PUFH ~±SE): males females [ PUFH +ve] PUIrit-ve ] 70.9"~-2.4 80.4-+-2.4 p=0.0075 [ 76.0"&2.6 [ 87.0"~.9 l p=0.01081
I
Conclusion: omeprazole, H2-bleekers and sucralfate were confirmed to signifieamb reduce GU relapses when compared with both no treatment and placebo. Male sex and positive PUFH must both be taken into account to predict GU relapse.
Sphi~r
H~rml at 16 cm at 21 cm ~ia~ % *(nun Hg) * ( m m H g ) pH<4 *(rain) Combined 70 79 65 52('32-75) 42(19-65) 28(17-46) Upright 66 48 45 64445-96) 44~'2g-74) 15(7.5~27) Supine 54 44 42 65(49-117) 63(4&-ST) 23(13-36) Leimecqumfie ranse m bcacgeta, t ' t ' m " e mem below the cn coidA defective sphincter was equally common in the three groups. Isolated refluxers had a similar prevalence of injury which was significantly lower than that of combined refuxers. Isolated supine refinxers had a significandy lower prevalence of hiatal hernia and had a higher c o n t r i t i o n amplitude in the diqal esophagus compared to combined reflnxers (p=0.01 at 16cm, p = 0 . 0 2 at 2tcm). The d u r a ~ n of the longnst reflux ephuxie was greatex in supine refluxe~ compared to upright refluxefs (p=0.04). Patients with combined reflux have more severe disease than patients with isolated reflux. However up to one half of the patients with isolated reflux have evidence of ~ injury and two thffds have a mechanically defective sphincter. O f intefeat isolated upright refluxess have lower distal esophageal contraction amplitudes than isolated supine refluxers. Given that upright refluxers have a high prevalence of a d ~ v e lower esophageal sphincter and often exhibit significant esophageal injury the reluctance to offer surgery to this group of patients may be unwarranted.