- Email: [email protected]
Prolonged acid suppression therapy is associated with gastric intestinal metaplasia and proximal gastric Helicobacter pylori colonisation
GASTROENTEROLOGY Vol. 114, No. 4
A156 AGA ABSTRACTS G0637
VALIDATION OF A RAPID CAPILLARY W H O L E BLOOD FINGER STICK TEST FOR DIAGNOSING H. PYLORI INFECTION IN GENERAL PRACTICE. GJB Hurenkamp 1, RWM van der Hulst2, HGLM Grundmeyer l, GNJ Tytgat2, A van der Ende 3. Departments of General Practice 1, Gastroenterology2 and Histopathology3, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Screening dyspeptic patients for H. pylori might help the general practitioner(GP) in his decision to refer a patient for endoscopy or to judge the usefulness of H. pylori eradication therapy. At present, culture and histopathology of gastric biopsies are considered as the gold standard for diagnosing H. pylori infection. However, endoscopy is inconvenient for screening purposes because of its invasive character and high costs. Therefore we investigated the accuracy of a desktop whole blood serology test in GPpractice and compared the results to the gold standard. Consecutive dyspeptic patients who were on maintenance acid suppressant therapy were referred for upper GI endoscopy. Gastric biopsies from antrum and corpus were taken for culture and histopathological examination. Whole blood QuickVue One-Step H. pylori serology test (Quidel Corporation, San Diego) was performed in the GP practice. The serology reading was done according to the instructions of the manufacturer. Diagnostic upper Gl-endoscopy was performed in 122 patients. Whole blood desktop serology was done in all patients. In two patients the serology was positive whereas the gastric biopsies were negative for H. pylori. In these patients successful eradication had been performed two to three years before as confirmed by repetitive biopsies for culture and histopathology. Discarding these two patients, 120 patients were eligible for analysis. The combination of culture and histopathology revealed H. pylori infection in 60 patients. Sensitivity and specificity of detecting 1t. pylori by culture of gastric biopsies was 98.3% and 100% respectively. Histological examination revealed H. pylori in 58 of 60 patients resulting in a sensitivity and specificity of 96.7% and 100% respectively. The desktop whole blood analysis revealed H. pylori infection in 52 of 60 patients resulting in a sensitivity of 86.7% and a specificity of 100% as compared to the gold standard. In 8 patients a false negative desktop result was found. Of these 8 patients 7 were positive when reassessed by the desktop test in hospital. Desktop serology is a reliable easy way to screen chronic dyspeptic patients on maintenance acid suppressant therapy for H. pylori infection in GP practice. Serology may be false positive even 3 years after apparent succesful H. pylori eradication. Desktop analysis may avoid endoscopy for detection of H. pylori infection. • G0638
54 kDa PROTEIN, BUT NOT 116 kDa PROTEIN, MAY BE CONSIDERED A SEROLOGICAL MARKER OF HELICOBACTER PYLOR1 POSITIVE GASTRIC CARCINOMA. G. laouinto. N. Giardullo, L. Pasquale, V. D'Onofrio, C. Panicu, A. Andriulli 1, F. Perri 1, C. Rega2, A. Todisco2, G. De Chiara2, W. Taccone2. Division of Gastroenterology and 2Clinical Pathology Laboratory, "San G Moscati" Hospital, Avellino, Italy, 1Division of Gastroenterology, IRCSS, San Govanni Rotondo, Foggia, Italy. Western blot analysis of systemic IgG responses to Helicobacter pylori has shown the antigenicity of 110-120kDa, g9kDa, 61kDa, 54kDa and 31 kDa proteins. 116kDa protein (CagA) and 89 kDa protein (VacA) are frequently produced by strains of H. pylori isolated from patients with gastric cancer as well as with duodenal ulcer; for this reason these proteins don't seem to represent specific serological markers of patients with H. pyloti positive gastric carcinoma. 54kDa protein has been considered one of the outer membrane proteins of H. pylori. Aim: To study the serological recognition of 116kDa, 89kDa and 54kDa proteins in H. pylori Giemsa positive patients with gastric carcinoma, duodenal ulcer and non ulcer dypepsia (NHD). Methods: 28 patients with gastric carcinoma (20 intestinal type, 8 diffuse type), 30 duodenal ulcer patients and 40 NUD were included in the study. Serum samples obtained from all patients were tested for IgG antibodies to 116kDa, 89kDa and 54 kDa proteins of H. pylori by Western blot technique Results: 26/28 (92.8%) patients with gastric carcinoma, 29•30 (96.7%) with duodenal ulcer and :30/40 (75.0%) with NUD were seropositive for 116 kDa protein. Serum IgG antibody to 116kDa protein in the cancer patients was not significantly higher than in both duodenal ulcer and NUD patients. Moreover, the detection of 89 kDa protein did not result significantly different between gastric carcinoma and NUD. Conversely, the serological responses to 54 kDa protein were significantly more prevalent in gastric cancer patients than in duodenal ulcer (p < 0.001) or NUD patients (p < 0.05). Protein
Gastric carcinoma
Duodenal ulcer
(%) (%) 116 kDa 92.8 96.7* 89 kDa 57.1 83.3** 54 kDa 78.6 36.7*** *p = ns vs Gastnc carcinoma; ** p < 0.05 vs Gastric carcinoma; *** p < 0.001 vs Gastric carcinoma
NUD
(%)
75.0* 60.0* 52.5**
Conclusions: In our study 1) the percentage of 116 kDa protein in the gastric
cancer was not significantly higher than in duodenal ulcer and NUD patients;
2) 54 kDa protein was almost always expressed in patients with gastric carcinoma; 3) 54 kDa protein, but not 116 kDa protein may be considered a serological marker distinguishing the gastric carcinoma from benign gastroduodenal diseases. G0639 PROLONGED ACID SUPPRESSION THERAPY IS ASSOCIATED WITH GASTRIC INTESTINAL METAPLASIA AND PROXIMAL GASTRIC HELICOBACTER PYLORI COLONISATION. H Ihmaldat, JJ Going*, H Kasem, C MacKay, RC Stuart. University Departments of Surgery & Pathology*, Glasgow Royal Infirmary, Scotland. Acid suppression therapy in the presence of Helicobacter pylori has been implicated in the development of chronic gastritis and glandular atrophy in the body of the stomach. The proposed mechanism is a proximal colonisation of the stomach by Helicobaeter pylori. It remains unclear whether this process can also affect the gastric mucosa at the squarnocolumnar junction where a high prevalence of intestinal metaplasia has been identified. AIMS: To investigate the relationship between duration of acid supression therapy and the presence of either Helicobacter pylori or intestinal rnetaplasia in the gastric mucosa at the squamocolumanr junction. PATIENTS: 169 consecutive dyspeptic patients attending for diagnostic upper gastro-intestinal endoscopy. METHODS: 3 biopsies were obtained from within 5cm of the pylorus and 3 from within 2cm of the squamocolumnar junction. Haematoxylin & Eosin, Alcian Blue pH2.5 - PAS, cresyl violet and immunohistochemistry for Helicobacter pylori were performed on all biopsies. Full drug histories were obtained and the duration of use of either proton pump inhibitors or 1-12receptor antagonists noted. Comparisons were calculated using the Mann-Whitney U test for nonparametric data. RESULTS: 48% (81) of patients were noted to have Helicobacter Pylori. 72% (58) of these individuals were noted to have both proximal and distal gastric colonisation while 18% (23) only had distal colonisation. The median length of time on acid suppression therapy in the 58 patients with dual colonisation was significantly greater than in the 23 with only distal infection (36, range 0-324 months vs 6, range 0-180 months: P < 0.05). 52% (88) were Helicbacter pylori negative. 68% of these had intestinal metaplasia within the stomach. The median length of time on acid suppression therapy in the Helicbacter pylori negative patients with intestinal metaplasia was significantly longer than in those without intestinal metaplasia (18, range 0216 months vs 9.5, range 0-192 months: P < 0.05). CONCLUSION: Prolonged acid suppresion therapy is associated with the proximal colonisation of the stomach by Helicobacter pylori. Interestingly, duration of acid suppresion therapy also appears to be an important independant factor in the development of intestinal metaplasia in the gastric mucosa at the squamocolumnar junction. • G0640
RECOVERY OF GASTRIC ACID SECRETION AND MUCOSAL ATROPHY AFTER H. PYLORI ERADICATION IN SEVERE ATROPHIC GASTRITIS. Katsunori Iijima, Shuichi Ohara, Hitoshi Sekine, Tomoyuki Koike, Yuji Kubota, Katsuaki Kato, Shigeru Asaki, T~tkayoshi Toyota. Internal Medicine(III), Tohoku University School of Medicine, Miyagi, Japan Backgrounds and Aims: H. pylori (HP) eradication has been reported to
improve gastric acid secretion in patients with corpus gastritis. However, such investigations referred to acid secretory movement after HP eradication have not been adequately supported by histological examination. Therefore, the present study aimed to evaluate the relation between restoration o f acid secretion and change of histological findings after HP eradication in patients with severe atrophic gastritis. Subjects and methods: 10 HP-positive patients (9 men, mean age 60 +_.11 y) treated intestinal-typed early gastric cancer with endoscopic mucosal resection were subject. Evaluation of stimulated acid output was performed by endoscopic gastrin test (EGT) which was a new endoscopic method of gastric secretory testing described in (Gastroenterology 112: A155, 1997) previously. The mean values of EGT in HP negative healthy men and women were 4.1_+1.5 and 2.6_+1.0 mEq/10min respectively. Biopsy specimens were taken endoscopically from upper gastric body. Histological evaluation was performed on the basis of Updated Sydney system and the degrees of inflammation, activity, and atrophy were scored from 0 to 3 respectively. All patients underwent HP eradication therapy and were successfully cured. EGT and endoscopic biopsy were performed during every endoscopy before and at 1 and 7 months after eradication. HP infection status was determined by histology, RUT, and t3C-UBT.
A156 AGA ABSTRACTS G0637
VALIDATION OF A RAPID CAPILLARY W H O L E BLOOD FINGER STICK TEST FOR DIAGNOSING H. PYLORI INFECTION IN GENERAL PRACTICE. GJB Hurenkamp 1, RWM van der Hulst2, HGLM Grundmeyer l, GNJ Tytgat2, A van der Ende 3. Departments of General Practice 1, Gastroenterology2 and Histopathology3, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Screening dyspeptic patients for H. pylori might help the general practitioner(GP) in his decision to refer a patient for endoscopy or to judge the usefulness of H. pylori eradication therapy. At present, culture and histopathology of gastric biopsies are considered as the gold standard for diagnosing H. pylori infection. However, endoscopy is inconvenient for screening purposes because of its invasive character and high costs. Therefore we investigated the accuracy of a desktop whole blood serology test in GPpractice and compared the results to the gold standard. Consecutive dyspeptic patients who were on maintenance acid suppressant therapy were referred for upper GI endoscopy. Gastric biopsies from antrum and corpus were taken for culture and histopathological examination. Whole blood QuickVue One-Step H. pylori serology test (Quidel Corporation, San Diego) was performed in the GP practice. The serology reading was done according to the instructions of the manufacturer. Diagnostic upper Gl-endoscopy was performed in 122 patients. Whole blood desktop serology was done in all patients. In two patients the serology was positive whereas the gastric biopsies were negative for H. pylori. In these patients successful eradication had been performed two to three years before as confirmed by repetitive biopsies for culture and histopathology. Discarding these two patients, 120 patients were eligible for analysis. The combination of culture and histopathology revealed H. pylori infection in 60 patients. Sensitivity and specificity of detecting 1t. pylori by culture of gastric biopsies was 98.3% and 100% respectively. Histological examination revealed H. pylori in 58 of 60 patients resulting in a sensitivity and specificity of 96.7% and 100% respectively. The desktop whole blood analysis revealed H. pylori infection in 52 of 60 patients resulting in a sensitivity of 86.7% and a specificity of 100% as compared to the gold standard. In 8 patients a false negative desktop result was found. Of these 8 patients 7 were positive when reassessed by the desktop test in hospital. Desktop serology is a reliable easy way to screen chronic dyspeptic patients on maintenance acid suppressant therapy for H. pylori infection in GP practice. Serology may be false positive even 3 years after apparent succesful H. pylori eradication. Desktop analysis may avoid endoscopy for detection of H. pylori infection. • G0638
54 kDa PROTEIN, BUT NOT 116 kDa PROTEIN, MAY BE CONSIDERED A SEROLOGICAL MARKER OF HELICOBACTER PYLOR1 POSITIVE GASTRIC CARCINOMA. G. laouinto. N. Giardullo, L. Pasquale, V. D'Onofrio, C. Panicu, A. Andriulli 1, F. Perri 1, C. Rega2, A. Todisco2, G. De Chiara2, W. Taccone2. Division of Gastroenterology and 2Clinical Pathology Laboratory, "San G Moscati" Hospital, Avellino, Italy, 1Division of Gastroenterology, IRCSS, San Govanni Rotondo, Foggia, Italy. Western blot analysis of systemic IgG responses to Helicobacter pylori has shown the antigenicity of 110-120kDa, g9kDa, 61kDa, 54kDa and 31 kDa proteins. 116kDa protein (CagA) and 89 kDa protein (VacA) are frequently produced by strains of H. pylori isolated from patients with gastric cancer as well as with duodenal ulcer; for this reason these proteins don't seem to represent specific serological markers of patients with H. pyloti positive gastric carcinoma. 54kDa protein has been considered one of the outer membrane proteins of H. pylori. Aim: To study the serological recognition of 116kDa, 89kDa and 54kDa proteins in H. pylori Giemsa positive patients with gastric carcinoma, duodenal ulcer and non ulcer dypepsia (NHD). Methods: 28 patients with gastric carcinoma (20 intestinal type, 8 diffuse type), 30 duodenal ulcer patients and 40 NUD were included in the study. Serum samples obtained from all patients were tested for IgG antibodies to 116kDa, 89kDa and 54 kDa proteins of H. pylori by Western blot technique Results: 26/28 (92.8%) patients with gastric carcinoma, 29•30 (96.7%) with duodenal ulcer and :30/40 (75.0%) with NUD were seropositive for 116 kDa protein. Serum IgG antibody to 116kDa protein in the cancer patients was not significantly higher than in both duodenal ulcer and NUD patients. Moreover, the detection of 89 kDa protein did not result significantly different between gastric carcinoma and NUD. Conversely, the serological responses to 54 kDa protein were significantly more prevalent in gastric cancer patients than in duodenal ulcer (p < 0.001) or NUD patients (p < 0.05). Protein
Gastric carcinoma
Duodenal ulcer
(%) (%) 116 kDa 92.8 96.7* 89 kDa 57.1 83.3** 54 kDa 78.6 36.7*** *p = ns vs Gastnc carcinoma; ** p < 0.05 vs Gastric carcinoma; *** p < 0.001 vs Gastric carcinoma
NUD
(%)
75.0* 60.0* 52.5**
Conclusions: In our study 1) the percentage of 116 kDa protein in the gastric
cancer was not significantly higher than in duodenal ulcer and NUD patients;
2) 54 kDa protein was almost always expressed in patients with gastric carcinoma; 3) 54 kDa protein, but not 116 kDa protein may be considered a serological marker distinguishing the gastric carcinoma from benign gastroduodenal diseases. G0639 PROLONGED ACID SUPPRESSION THERAPY IS ASSOCIATED WITH GASTRIC INTESTINAL METAPLASIA AND PROXIMAL GASTRIC HELICOBACTER PYLORI COLONISATION. H Ihmaldat, JJ Going*, H Kasem, C MacKay, RC Stuart. University Departments of Surgery & Pathology*, Glasgow Royal Infirmary, Scotland. Acid suppression therapy in the presence of Helicobacter pylori has been implicated in the development of chronic gastritis and glandular atrophy in the body of the stomach. The proposed mechanism is a proximal colonisation of the stomach by Helicobaeter pylori. It remains unclear whether this process can also affect the gastric mucosa at the squarnocolumnar junction where a high prevalence of intestinal metaplasia has been identified. AIMS: To investigate the relationship between duration of acid supression therapy and the presence of either Helicobacter pylori or intestinal rnetaplasia in the gastric mucosa at the squamocolumanr junction. PATIENTS: 169 consecutive dyspeptic patients attending for diagnostic upper gastro-intestinal endoscopy. METHODS: 3 biopsies were obtained from within 5cm of the pylorus and 3 from within 2cm of the squamocolumnar junction. Haematoxylin & Eosin, Alcian Blue pH2.5 - PAS, cresyl violet and immunohistochemistry for Helicobacter pylori were performed on all biopsies. Full drug histories were obtained and the duration of use of either proton pump inhibitors or 1-12receptor antagonists noted. Comparisons were calculated using the Mann-Whitney U test for nonparametric data. RESULTS: 48% (81) of patients were noted to have Helicobacter Pylori. 72% (58) of these individuals were noted to have both proximal and distal gastric colonisation while 18% (23) only had distal colonisation. The median length of time on acid suppression therapy in the 58 patients with dual colonisation was significantly greater than in the 23 with only distal infection (36, range 0-324 months vs 6, range 0-180 months: P < 0.05). 52% (88) were Helicbacter pylori negative. 68% of these had intestinal metaplasia within the stomach. The median length of time on acid suppression therapy in the Helicbacter pylori negative patients with intestinal metaplasia was significantly longer than in those without intestinal metaplasia (18, range 0216 months vs 9.5, range 0-192 months: P < 0.05). CONCLUSION: Prolonged acid suppresion therapy is associated with the proximal colonisation of the stomach by Helicobacter pylori. Interestingly, duration of acid suppresion therapy also appears to be an important independant factor in the development of intestinal metaplasia in the gastric mucosa at the squamocolumnar junction. • G0640
RECOVERY OF GASTRIC ACID SECRETION AND MUCOSAL ATROPHY AFTER H. PYLORI ERADICATION IN SEVERE ATROPHIC GASTRITIS. Katsunori Iijima, Shuichi Ohara, Hitoshi Sekine, Tomoyuki Koike, Yuji Kubota, Katsuaki Kato, Shigeru Asaki, T~tkayoshi Toyota. Internal Medicine(III), Tohoku University School of Medicine, Miyagi, Japan Backgrounds and Aims: H. pylori (HP) eradication has been reported to
improve gastric acid secretion in patients with corpus gastritis. However, such investigations referred to acid secretory movement after HP eradication have not been adequately supported by histological examination. Therefore, the present study aimed to evaluate the relation between restoration o f acid secretion and change of histological findings after HP eradication in patients with severe atrophic gastritis. Subjects and methods: 10 HP-positive patients (9 men, mean age 60 +_.11 y) treated intestinal-typed early gastric cancer with endoscopic mucosal resection were subject. Evaluation of stimulated acid output was performed by endoscopic gastrin test (EGT) which was a new endoscopic method of gastric secretory testing described in (Gastroenterology 112: A155, 1997) previously. The mean values of EGT in HP negative healthy men and women were 4.1_+1.5 and 2.6_+1.0 mEq/10min respectively. Biopsy specimens were taken endoscopically from upper gastric body. Histological evaluation was performed on the basis of Updated Sydney system and the degrees of inflammation, activity, and atrophy were scored from 0 to 3 respectively. All patients underwent HP eradication therapy and were successfully cured. EGT and endoscopic biopsy were performed during every endoscopy before and at 1 and 7 months after eradication. HP infection status was determined by histology, RUT, and t3C-UBT.