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The influence of gastroparesis on gastroesophageal reflux disease (GERD)
GASTROENTEROLOGYVol. 114, No. 4
AlaS AGA ABSTRACTS G0769 HAS ERADICATION OF HELICOBACTER PYLORI REALLY HAD NEGATIVE INFLUENCE ON THE PATIENTS CHRONICALLY TAKING NSAIDS? H. Kordecki, R. Kosik. Dept. of Gastroenterology M.Curie Hospital, Szczecin, Poland The majority of last reports connected with the role of COX-toxicity in the NSAIDs-users suggested the benifits of H.p. infection for the patients. On the contrary in our earlier presentation we noticed that eradication of H. pylori (H.p.) in persons with some mucosal changes being protractedly treated with NSAIDs may be more optimal and cheaper method in comparison with those continually taking prostaglandins (e.g. misoprostol) or H-2 blockers (famotidine) [GUT 1996,39,suppl.2, A27]. The aim of this study was to estimate the relapse rate of mucosal lesions two years after the end of therapy in persons chronically taking NSAIDs. Eradication of H.p. was carded out in all the patients. Additionally we attempted to find out if affinity to one of the COX-2 types was an essential element having influence on the sensfulness of H.p. eradication. Material and methods: Endoscopic examinations were performed (EVIS 100 Olympus equipment) in 194 patients receiving chronically NSAIDs. In 153 persons (79%) taking NSAIDs leasions were found: 124 patients stomach erosions, 75 stomach ulcers, 89 duodenal erosions and 71 duodenal ulcers. Thirty-nine were diagnosed to have multiple ulceration and erosions. In 106 (69%) out of this group H.p. infection was disclosed. However negative results were detected in 47 patients (29%). Patients who had mucosal lesions in stomach or/and duodenum were treated by one of these four methods: 1. colloidal bismuth with amoxicillin and metronidazole (CB+A+M) 2. omeprazole with amoxiciUin and metronidazole (O+A+M) 3. omeprazole with clarithromycin and tinidazole (O+C+T) After 24 months post mentioned therapy the endoscopic examination was repeated in 105 patients without any abdominal pain and treated as formerly with NSAIDs. Results: Method of eradication therapy CB+A+M O+A+M O+C+T
No of patients before after H.p. eradicat, 51 18 66 55 36 32
one month after therapy two years after therapy healings eradicat. healings eradicat. rate rate rate rate 38 (75%) 11 (22%) 8 (44%) 5 (28%) 58 (88%) 38 (58%) 49 (89%) 27 (49%) 34 (94%) 29 (81%) 30 (94%) 26 (81%)
Conclusions: 1. The best method resulting in long-term-healing end eradication of H.p. was the Bazzoli regimen. 2. Our further investigation confirms earlier opinion about the value of H.p. eradication in patients protratractedly treated with NSAIDs. 3. Moreover, the majority of patients were taking drugs from both groups of COX-toxicity, therefore it was not possible to answer if the difference between them has any influence on H.p. status. G0770 THE INFLUENCE OF HELICOBACTER PYLORI ON GASTRIC AND DUODENAL MUCOSA INJURED BY ACETYLSALICYLIC ACID. Kordecki H., Kurowski M.*, Kosik R., Pilecka D. Dept. of Gastrology & Cardiology* M.Curie Hospital, Szczecin, Poland In our previous studies we showed significantly higher percentage of Helicobacter pylori (H.p.) infection and higher incidence of mucosal lesions in upper digestive tract in patients suffering from ischaemic heart disease (IHD) and chronically treated with acetylsalicylic acid (ASA). However, experimental studies published by Konturek et al showed mucosa adaptation to repeated doses of ASA. This phenomenon can be explained by pathological reaction of gastric mucosa in the presence of Helicobacter pylori. The aim of our study was to estimate the relation between the frequency of m.1. in both stomach and duodenum and the daily dose of ASA as well as the influence of H.p. eradication on m.1. occurrence during eontinous treatment with ASA. Patients were taking ASA in doses: 75 or 150 or 300 mg per day for at least four weeks prior to the first endoscopy.Eradication was conducted according to Bazzoli regimen and its efficancy was about 90%. In refractory patients the quadriple-therapy was used. Seventy eight patients agreed to repeat the endoscopy during the period of 18 months. Results:
Total number of ASA users patients taking: 300 mg ASA per day 150 mg ASA per day 75 mg ASA per da~¢ Patients not taking AS.~ Control group
Mucosal lesions before therapy
Mucosal lesions I0 months after therap)'
No. of patients before/after therapy
Hp positive before therapy
163/78
110 (68%)
93 (57%)
24 (31%)
21110 53/21 89/47 80 50
15 (71%) 42 (79%) 53 (74%) 38 (47%) 13 (26%)
19 (90%) 38 (72%) 36 (40%) 33 (41%) 4 (8%)
6 (60%) 10 (48%) 8 (17%)
Conclusion: 1. Decreasing the daily dose of ASA from 300 to 75 mg decreased the frequency of mucosal lesions occurrence but had no influence on the frequency of Hp infection. 2. The results of our study confirm the views that H.p. eradication is an effective method in prevention of m.1. development in patients chronically treated with ASA. 3. Our results do not
confirm the opinion that H.p.-LPS can induce gastroprotection by increasing cyclooxygenase 2 activity and prostaglandin synthesis. • G0771 EFFECTS OF H. PYLORI AND INTERLEUKIN-8 ON HISTAMINE RELEASE FROM ISOLATED HUMAN GASTRIC MUCOSAL MAST CELLS. M Kovana~,i, K Yakabi, T Arimura, Y Uehigashi, N Wada, T Nakamura. The Third Department of Internal Medicine, Surgery, Teikyo University School of Medicine Ichihara hospital, Chiba, Japan Background; Helicobacter pylori(H, pylori) is now recognized as the main cause of peptic ulcer and Type B gastritis. However the details of the pathophysiology of the infection are not fully elucidated. In H. pylori infection, redness and edema of gastric mucosa were seen in the endoscopic examination for which chemokines such as histamine, leukotriene B4 and PAF might be responsible. In this study, we undertook to elucidate effects of H. pylori and interleukin8(IL-8) on histamine release from isolated human gastric mucosal mast cells. Methods; Human fundic mucosa from the resected stomach for gastric cancer was digested with collagenase and EDTA. Isolated gastric mucosal cells were separated by Beckman elutriator rotor followed by Nycodenz density gradient centrifugation. Mast cells were finally enriched to 50% which were identified by toluidine blue staining, immnnostainings with anti histamine antibody and anti mast cell tryptase antibody and electron microscopy. Enriched mast cells were incubated in the EBSS medium with H. pylori sonicate, water extract and IL-8 for 15rain at 37°C. Contents of histamine were assayed by histamine RIA Kit(IMMUNO TECK). Results; The second small cells fraction (mast cell enriched fraction) released the greatest amount of histamine in all cell fractions. Sonicate and water extract of H. pylori increased histamine release from mast cells by 115%(P < 0.01) and 97%(P < 0.01) above the basal state. IL-8(50ng/ml) also increased histamine release by 57% above the basal state. Dose-dependent stimulation on histamine release by the concentrations(20~100ng/ml) of IL-8 were seen. The maximal stimulation on histamine release was seen at the concentration of 50ng/ml of IL-8. Conclusion; The results indicated that H. pylori and IL-8 had stimulatory effects on histamine release from human gastric mucosal mast cells. Soluble factors of H. pylori and IL-8 might accelerate the inflammation of gastric mucosa via histamine release from mast cells. G0772 THE INFLUENCE OF GASTROPARESIS ON GASTROESOPHAGEAL REFLUX DISEASE (GERD). S. Kress, D. Dorlars, A. Buttmann, P. Schauwecker, J.F. Riemann Dept. of Gastroenterology, Klinikum Ludwigshafen, Germany Aim: GERD's current hypothesis of pathogenesis is multifactorial. Gastroparesis is one cause, but it's influence on GERD is not yet fully understood. Materials and Methods: A prospective study of 69 patients suffering from GERD was carded out, using the methods of endoscopy, esophagus-pHmonitoring (Normal value; Dig Dis Sci, 1992;37:849-856), solide-state esophageal manometry and measurement of gastric emptying time using either ultrasound (Dtsch Med Wschr 1994; 119:575-580) or Cl3-octanoic acid breath testing (Dig Dis Sci 1994; 39:104-106). The cut off for a normal gastric emptying was 40 min. (ultrasound testing) and 80 min. (C 13-octanoic acid breath testing). The results from Group 1, those with gastroparesis (n=46) were compared with those from Group 2, without gastroparesis (n=23) using Mann-Whitney U-test and chi-square testing. Results: The two groups show no statistical difference according to the following parameters; age, endoscopy reflux grading (Savary Miller), presence of hiatus hernia; manometric findings and almost all pH monitoring findings. Only the" Total refluxtime in an upright position in percent (pH < 4)" was significantly higher and in more cases pathologic, in group 1 than in group 2. Also more women were identified as suffering from gastroparesis. Gastroparesis Total reflux time in upright position # Pathologic (more than 8,1% < pH 4) # Physiologic (less than 8,1% < pH 4) Total
9 14 23
+
P
30 16 46
0,03933
Conclusion: Gastroparesis is only influential on refluxepisodes when the patient is in an upright position. Endocopic reflux grading is similar in patients with gastroparesis as in those without gastroparesis. G0773 LONG-TERM EFFECTS OF ACID SUPPRESSION ON Nd:YAG LASER TREATED BARRETT'S ESOPHAGUS: ONGOING STUDIES. B Krevsky, B Horwitz, S Cohen, RS Fisher. Temple University School of Medicine, Philadelphia, PA. Endoscopic Nd:YAG laser therapy (ELT) can convert Barrett's Esophagus (BE) to normal squamous epithelium - but will it last? This study was designed to determine whether long-term acid suppression can maintain the restoration of normal epithelium after treatment by ELT. Methods: Patients
AlaS AGA ABSTRACTS G0769 HAS ERADICATION OF HELICOBACTER PYLORI REALLY HAD NEGATIVE INFLUENCE ON THE PATIENTS CHRONICALLY TAKING NSAIDS? H. Kordecki, R. Kosik. Dept. of Gastroenterology M.Curie Hospital, Szczecin, Poland The majority of last reports connected with the role of COX-toxicity in the NSAIDs-users suggested the benifits of H.p. infection for the patients. On the contrary in our earlier presentation we noticed that eradication of H. pylori (H.p.) in persons with some mucosal changes being protractedly treated with NSAIDs may be more optimal and cheaper method in comparison with those continually taking prostaglandins (e.g. misoprostol) or H-2 blockers (famotidine) [GUT 1996,39,suppl.2, A27]. The aim of this study was to estimate the relapse rate of mucosal lesions two years after the end of therapy in persons chronically taking NSAIDs. Eradication of H.p. was carded out in all the patients. Additionally we attempted to find out if affinity to one of the COX-2 types was an essential element having influence on the sensfulness of H.p. eradication. Material and methods: Endoscopic examinations were performed (EVIS 100 Olympus equipment) in 194 patients receiving chronically NSAIDs. In 153 persons (79%) taking NSAIDs leasions were found: 124 patients stomach erosions, 75 stomach ulcers, 89 duodenal erosions and 71 duodenal ulcers. Thirty-nine were diagnosed to have multiple ulceration and erosions. In 106 (69%) out of this group H.p. infection was disclosed. However negative results were detected in 47 patients (29%). Patients who had mucosal lesions in stomach or/and duodenum were treated by one of these four methods: 1. colloidal bismuth with amoxicillin and metronidazole (CB+A+M) 2. omeprazole with amoxiciUin and metronidazole (O+A+M) 3. omeprazole with clarithromycin and tinidazole (O+C+T) After 24 months post mentioned therapy the endoscopic examination was repeated in 105 patients without any abdominal pain and treated as formerly with NSAIDs. Results: Method of eradication therapy CB+A+M O+A+M O+C+T
No of patients before after H.p. eradicat, 51 18 66 55 36 32
one month after therapy two years after therapy healings eradicat. healings eradicat. rate rate rate rate 38 (75%) 11 (22%) 8 (44%) 5 (28%) 58 (88%) 38 (58%) 49 (89%) 27 (49%) 34 (94%) 29 (81%) 30 (94%) 26 (81%)
Conclusions: 1. The best method resulting in long-term-healing end eradication of H.p. was the Bazzoli regimen. 2. Our further investigation confirms earlier opinion about the value of H.p. eradication in patients protratractedly treated with NSAIDs. 3. Moreover, the majority of patients were taking drugs from both groups of COX-toxicity, therefore it was not possible to answer if the difference between them has any influence on H.p. status. G0770 THE INFLUENCE OF HELICOBACTER PYLORI ON GASTRIC AND DUODENAL MUCOSA INJURED BY ACETYLSALICYLIC ACID. Kordecki H., Kurowski M.*, Kosik R., Pilecka D. Dept. of Gastrology & Cardiology* M.Curie Hospital, Szczecin, Poland In our previous studies we showed significantly higher percentage of Helicobacter pylori (H.p.) infection and higher incidence of mucosal lesions in upper digestive tract in patients suffering from ischaemic heart disease (IHD) and chronically treated with acetylsalicylic acid (ASA). However, experimental studies published by Konturek et al showed mucosa adaptation to repeated doses of ASA. This phenomenon can be explained by pathological reaction of gastric mucosa in the presence of Helicobacter pylori. The aim of our study was to estimate the relation between the frequency of m.1. in both stomach and duodenum and the daily dose of ASA as well as the influence of H.p. eradication on m.1. occurrence during eontinous treatment with ASA. Patients were taking ASA in doses: 75 or 150 or 300 mg per day for at least four weeks prior to the first endoscopy.Eradication was conducted according to Bazzoli regimen and its efficancy was about 90%. In refractory patients the quadriple-therapy was used. Seventy eight patients agreed to repeat the endoscopy during the period of 18 months. Results:
Total number of ASA users patients taking: 300 mg ASA per day 150 mg ASA per day 75 mg ASA per da~¢ Patients not taking AS.~ Control group
Mucosal lesions before therapy
Mucosal lesions I0 months after therap)'
No. of patients before/after therapy
Hp positive before therapy
163/78
110 (68%)
93 (57%)
24 (31%)
21110 53/21 89/47 80 50
15 (71%) 42 (79%) 53 (74%) 38 (47%) 13 (26%)
19 (90%) 38 (72%) 36 (40%) 33 (41%) 4 (8%)
6 (60%) 10 (48%) 8 (17%)
Conclusion: 1. Decreasing the daily dose of ASA from 300 to 75 mg decreased the frequency of mucosal lesions occurrence but had no influence on the frequency of Hp infection. 2. The results of our study confirm the views that H.p. eradication is an effective method in prevention of m.1. development in patients chronically treated with ASA. 3. Our results do not
confirm the opinion that H.p.-LPS can induce gastroprotection by increasing cyclooxygenase 2 activity and prostaglandin synthesis. • G0771 EFFECTS OF H. PYLORI AND INTERLEUKIN-8 ON HISTAMINE RELEASE FROM ISOLATED HUMAN GASTRIC MUCOSAL MAST CELLS. M Kovana~,i, K Yakabi, T Arimura, Y Uehigashi, N Wada, T Nakamura. The Third Department of Internal Medicine, Surgery, Teikyo University School of Medicine Ichihara hospital, Chiba, Japan Background; Helicobacter pylori(H, pylori) is now recognized as the main cause of peptic ulcer and Type B gastritis. However the details of the pathophysiology of the infection are not fully elucidated. In H. pylori infection, redness and edema of gastric mucosa were seen in the endoscopic examination for which chemokines such as histamine, leukotriene B4 and PAF might be responsible. In this study, we undertook to elucidate effects of H. pylori and interleukin8(IL-8) on histamine release from isolated human gastric mucosal mast cells. Methods; Human fundic mucosa from the resected stomach for gastric cancer was digested with collagenase and EDTA. Isolated gastric mucosal cells were separated by Beckman elutriator rotor followed by Nycodenz density gradient centrifugation. Mast cells were finally enriched to 50% which were identified by toluidine blue staining, immnnostainings with anti histamine antibody and anti mast cell tryptase antibody and electron microscopy. Enriched mast cells were incubated in the EBSS medium with H. pylori sonicate, water extract and IL-8 for 15rain at 37°C. Contents of histamine were assayed by histamine RIA Kit(IMMUNO TECK). Results; The second small cells fraction (mast cell enriched fraction) released the greatest amount of histamine in all cell fractions. Sonicate and water extract of H. pylori increased histamine release from mast cells by 115%(P < 0.01) and 97%(P < 0.01) above the basal state. IL-8(50ng/ml) also increased histamine release by 57% above the basal state. Dose-dependent stimulation on histamine release by the concentrations(20~100ng/ml) of IL-8 were seen. The maximal stimulation on histamine release was seen at the concentration of 50ng/ml of IL-8. Conclusion; The results indicated that H. pylori and IL-8 had stimulatory effects on histamine release from human gastric mucosal mast cells. Soluble factors of H. pylori and IL-8 might accelerate the inflammation of gastric mucosa via histamine release from mast cells. G0772 THE INFLUENCE OF GASTROPARESIS ON GASTROESOPHAGEAL REFLUX DISEASE (GERD). S. Kress, D. Dorlars, A. Buttmann, P. Schauwecker, J.F. Riemann Dept. of Gastroenterology, Klinikum Ludwigshafen, Germany Aim: GERD's current hypothesis of pathogenesis is multifactorial. Gastroparesis is one cause, but it's influence on GERD is not yet fully understood. Materials and Methods: A prospective study of 69 patients suffering from GERD was carded out, using the methods of endoscopy, esophagus-pHmonitoring (Normal value; Dig Dis Sci, 1992;37:849-856), solide-state esophageal manometry and measurement of gastric emptying time using either ultrasound (Dtsch Med Wschr 1994; 119:575-580) or Cl3-octanoic acid breath testing (Dig Dis Sci 1994; 39:104-106). The cut off for a normal gastric emptying was 40 min. (ultrasound testing) and 80 min. (C 13-octanoic acid breath testing). The results from Group 1, those with gastroparesis (n=46) were compared with those from Group 2, without gastroparesis (n=23) using Mann-Whitney U-test and chi-square testing. Results: The two groups show no statistical difference according to the following parameters; age, endoscopy reflux grading (Savary Miller), presence of hiatus hernia; manometric findings and almost all pH monitoring findings. Only the" Total refluxtime in an upright position in percent (pH < 4)" was significantly higher and in more cases pathologic, in group 1 than in group 2. Also more women were identified as suffering from gastroparesis. Gastroparesis Total reflux time in upright position # Pathologic (more than 8,1% < pH 4) # Physiologic (less than 8,1% < pH 4) Total
9 14 23
+
P
30 16 46
0,03933
Conclusion: Gastroparesis is only influential on refluxepisodes when the patient is in an upright position. Endocopic reflux grading is similar in patients with gastroparesis as in those without gastroparesis. G0773 LONG-TERM EFFECTS OF ACID SUPPRESSION ON Nd:YAG LASER TREATED BARRETT'S ESOPHAGUS: ONGOING STUDIES. B Krevsky, B Horwitz, S Cohen, RS Fisher. Temple University School of Medicine, Philadelphia, PA. Endoscopic Nd:YAG laser therapy (ELT) can convert Barrett's Esophagus (BE) to normal squamous epithelium - but will it last? This study was designed to determine whether long-term acid suppression can maintain the restoration of normal epithelium after treatment by ELT. Methods: Patients