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Helicobacter pylori and non-Helicobacter pylori bacterial flora before and after eradication therapy for Helicobacter pylori
Abstracts /Netherlands
Journal of Medicine 48 (1996) Al -A42
0.03%, 87.5% :; 0.05%, 94.4% < 0.07%) and were considered to be “true negatives”. Two of the 4 patients with a breath test result in the grey zone underwent repeat endoscopy which showed them to be H. pylon’-negative in CLO, histology and culture of antral and corpus biopsies. They were therefore considered to have had a “false positive” breath test result. The other two still need to be endoscoped. Conclusion: In this first Dutch long term follow-up study the great majority of successfully treated ulcer patients have remained free of infection, thus demonstrating that H. pylon’ eradication is a.stable phenomenon over time. In the follow-up period of more then 2 years the recurrence rate of H. pykwi was found to be at most 2/72 (30/o), demonstrating that re-infections a:re rare in Holland. The 2 patients we consider positive, however, could have had a false-positive breath test result and they can only be classified properly after repeat endoscopy. No difference in recurrence rate was found in patients initially treated with 1 week versus 2 weeks of quadruple therapy. This observation substantiates the claim that 1 week of quadruple therapy is sufficient to cure ulcer patients. Only 4 days of quadruple therapy can effectively cure Helicobu&r pylon’ infkction. W.A. de Boer ‘, W.M.M. Driessen 2. Departments of Internal Medicine, ’ Sint Anna Ziekenhuis, Oss and ’ Sint Joseph Ziekenhuis, Veldhoven, Netherlands.
We have promoted 7 days of quadruple therapy (bismuth, tetracycline, metronidazole and omeprezole) as the optimal anti-Helicobaaer treatment because it is highly effective ( > 95% cure), is independent of metronidazole resistance, and has good patient tolerability. In this study we investigated whether treatment duration can be reduced to 4 days. Fiftyfour patients [34 men, 20 women, 21 (39%) smokers with functional dyspepsia or peptic ulcer disease ad biopsy-proven H. pylon’ infection] received omeprazole 20 mg b.d. days l-7, colloidal bismuth subcitrate 120 mg q.i.d. days 4-7, tetracycline 500 mg q.i.d. days 4-7 and metronidazole 500 mg days 4-7. At least .5 weeks after therapy a second endoscopy was performed in all with 10 biopsies: 2 (antrum) for CL0 test, 2 (antrum) for culture and 6 (2 antrum, 2 cardia, 2 corpus) for histology (Giemsa stain). A patient was considered cured if all 3 tests were negative. All patient,5 finished the treatment but two had a 14C-urea breath test instead of endoscopy to confirm cure. Side-effects did not interfere with compliance. 49/54 patients (91%, 95% confidence inlerval SO-97%) were cured of their H. pylon’ infection. In 43/54 patients pre-treatment metronidazole resistance was known; of these 38/40 (95%) with a metronidazole-sensitive strain and 1 of 3 with a metronidazole-resistant strain were cured. Conclusion: We found 4 days of quadruple therapy after omeprazole pretreatment to be a well-tolerated but above all effective treatment for H. pylon’ infection, especially in those carrying a me:tronidazole-sensitive strain. Our results need confirmation to allow recommendation, but for patients suffering from side-effects on the 7-day quadruple regimen it seems possible to interrupt treatment after 4 days. Moreover,
Al5
these data suggest that for 7-day quadruple therapy, comphante is less critical than for other regimens.
Effects of eradicating H. pylon’ on symptoms in non-ulcer dyspepsia patients. M.L. Verhulst, W.P.M. Hopman, J.B.M.J. Jansen. Department of Gastroenterology and Hepatology, University Hospital, Nijmegen, Netherlands. The effects of eradicating H. pylon (Hp) on symptoms in
patients with non-ulcer dyspepsia (NUD) remains unclear. Some studies have shown a decrease in symptom scores after eradicating Hp, whereas others did not find such a decrease. The follow-up period in most studies is unfortunately very short. We therefore studied the effects of eradicating Hp on upper abdominal complaints in NUD patients. Thirty-nine HP-positive, NUD patients (25M, 14F) were studied. Before, immediately after 1 month after and > 1 year after Hp eradication therapy, symptoms like epigastric pain, nausea vomiting, pyrosis, belching, bloating and bad smell were scored on a visual analog scale. One month after eradication therapy endoscopy was performed and biopsies for HP culture, CL0 test and histology were taken. One month after eradication therapy Hp was eradicated in 21 of 39 patients (54%). The overall symptom scores significantly (p < 0.001) decreased from 24*2 before therapy to 8+ 2 immediately after therapy to 11 + 1 at 1 month after therapy and to 11+2 at 1 year after therapy in patients where HP was eradicated. In patients where Hp was not eradicated the overall symptom scores also gradually decreased, from 24+3 to 18f4 immediately after therapy (p = 0.08), form 24+3 to 15k2 at 1 month after therapy (p < O.OOS),and from 24*3 to 13 &-3 at > 1 year after therapy (p < 0.001). The differences in symptom scores between the patients in whom Hp was eradicated and in whom Hp was not eradicated were only significant (p < 0.05) immediately after eradication therapy. Conclusions: This study demonstrates that symptoms related to NUD significantly decrease in response to eradication therapy for Hp, not only in patients where Hp was eradicated, but also in those where Hp was not eradicated. Symptom scores in patients where Hp was eradicated were only significantly better than symptom scores in patients in whom eradication therapy had failed, immediately after therapy. Thereafter, no differences between the two groups were observed during a follow-up period of more than 1 year.
Hekcobader pylon’ and non- Hehwbader pybi bacterial flora before and after eradication therapy for Helicobucrer pylori. D.
Jonkers ‘, P. Houben ‘, A. de Bruine ‘, E. Stobberingh 3, R. Stockbriigger ‘. Departments of I Gastroenterology, 2 Pathology, and 3 Microbiology, University Hospital, Maastricht, Netherlands. Eradication of H. pylori by gastric acid inhibition in com-
bination with antibiotics can result in overgrowth of non-H. pykwi bacterial flora. This may confound the detection of H.
pylori. To assessthe intragastric bacterial flora, in 18 patients treated with amoxycillin (2 weeks) and omeprazole (6 weeks),
A16
Abstracts/Netherlands
Journal
gastric juice was cultured and two biopsies each of duodenum. antrum and corpus were obtained before and at the end of eradication therapy for culture and for histology by modified Giemsa (MG) and immunohistochemistry (IMM) against H. pylon’, respectively. Numbers of patients with H. pylori-positive and non-H. pylon’ positive biopsies by each method are shown in the table. Culture showed a significant increase in amount of oral flora (p < 0.05) in gastric juice, duodenal, antral and body mucosa after therapy. After therapy with culture as standard, sensitivity and specificity of MG were 60.7 and 80.9%, and of IMM 80.3 and 89.4%, respectively. Specimen
Before therapy Culture IMM HP HP non-HP
G. juice * Corpus Antrum Duod.
1 15 15 14
0 3 7 2
13 16 10
After therapy MG HP 11 17 5
Culture IMM HPP HP non-HP
MG HP
0 9 7 1
5 6 2
11 13 13 15
9 6 0
* Mean pH gastric juice: 1.4 (n = 18) before and 5.1 (n = 17) after eradication therapy, still on omeprazole 20 mg b.i.d. Conclusion: IMM is superior to MG for the detection of H. pylon’. Because of the possible presence of non-H. pylon’ flora after eradication therapy the use of IMM is recommended in this situation. Helicobacter pylori in gastric MALT lymphoma. I. Gisbertz lX3,
D. Jonkers ‘x2, J.W. Arends 3, R. Stockbriigger ‘, H.C. Schouten ‘. Departments of ’ Internal Medicine, ‘Microbiology and 3 Pathology, University Hospital, Maastricht, Netherlands.
Gastric mucosa-associated lymphoid tissue (MALT) tumours develop possibly in response to local infection by Helicobacter pylon’ (HP). We investigated the presence of Hp and non-HP intragastric bacterial flora in 26 patients with gastric MALT lymphoma, classified as low-grade (9 cases) or high-grade histology (17 cases). Serial sections were stained with haematoxylin-eosin, modified Giemsa, and immunohistochemically with a specific polyclonal antibody for Hp. Fourteen patients (54%) showed presence of Hp in the mucosa surrounding the tumour. In the tumour no presence of Hp was found. In 16 patients (61%), other bacteria (non-HP) were seen. The table shows the distribution of bacterial flora among low- and high-grade MALT lymphomas. The percentage of HP-positive cases in our study (54%) is lower than that reported in the literature (about 90%). This could be due to less specific staining methods, overestimating the presence of Hp or to the fact that those figures mainly represent low-grade MALT lymphomas. H. pylon’
Other bacteria
Low grade (n = 9) (mean age 58.5; 7 6,2? 1
6 (67%)
4 (44%)
High grade (n = 17) (mean age 61.9; 86,9?)
8 (47%)
12 (71%)
qf Medicine 48 (I9961 Al -A42 Conclusions: (1) Using a specific staining method for Hp, the prevalence of Hp in patients with gastric MALT lymphoma is probably not different from the normal population. (2) Hp is found in a similar frequency in low and high grade gastric MALT lymphomas. (3) Our results suggestthat non-Hip bacterial flora may play a role in the development of MALT. ca&4 status of Hehbacter
pylori in gastric MALT Iymphema.
D. de Jong ‘, H. Boot ‘, B.G. Taal’, W. van Dijk ‘, E. Kuipers 4, G. Pals ‘. Departments of ’ Pathology and ’ Gastroenterology, Antoni van Leeuwenhoek Ziekenhuis, Amsterdam; “Bacteriology, Sloteruaart Ziekenhuis, Amsterdam; 4 Gastroenterology and 5 Human Genetics, Free University, Amsterdam, Netherlands.
There is increasing evidence that persistent infection with Helicobacter pylon’ (HP) is a risk factor for development of
gastric adenocarcinoma as well as primary gastric non-Hodgkin’s lymphoma of mucosa-associated(MALT) type. Approximately 50% of HP isolates possess a gene, cagA, which encodes a high-molecular-weight protein of variable size that is highly associated with vacA expression. It has been shown that cagrl-positive strains are associated with enhanced acute inflammation and with peptic ulcer disease and therefore identify more aggressive strains. Also an increased risk for development of atrophic gastritis during long-term follow-up and a slightly increased risk for development of gastric cancer, especially of intestinal type, has been reported. In this study, we investigated the relation between cagA status and gastric MALT-NHL. Fifteen bacterial strains isolated from 10 patients with gastric MALT-NHL were analyzed using a cagA PCR assay. In 6 patients a cagrl-specific PCR-product was found. Four patients had a cad-negative strain. In 3 patients, multiple bacterial isolates, collected during follow-up, were analyzed. In all cases, consistent results were found (2 cagApos, 1 cagA-neg). As controls, 58 patients with chronic HP infection were analysed for serum antibodies to cagA using an ELISA assay. It has been shown that cagA status as determined by PCR and ELISA assays correlate to a very high extent. Due to infection with multiple strains, serum analysis may give somewhat higher cag,4-positive incidences. PCR analysis is more sensitive, however: 24/58 (41%) subjects were cagA-positive, 34/58 (59%) were cad-negative. During follow-up, 26 patients developed atrophic gastritis, of whom 60% were cag,4-positive;9/32 (30%) patients without atrophic gastritis were cagA-positive. Conclusions: These preliminary results indicate that similarly to gastric adenocarcinoma also gastric MALT-NHL is related to cagrl-positive HP strains. cagA-positive HP strains are reported to induce a significantly higher local and systemic immune reaction. The chronic local immune reaction can be recognized as induced MALT and is considered to harbour the precursor population of MALT-NHL. Helicobacter pylon’ eradication and gastric MALT lymphoma - early results. H. Boot ‘, D. de Jong ‘, P. van Heerde ‘, J.V.M. Burgers 3, B.G. Taal I. Departments of I Gastroenterology, 2 Pathology and 3 Radiotherapy, Netherlands Cancer Institute / Antoni van Leeuwenhoekhuis, Amsterdam, Netherlands.
Journal of Medicine 48 (1996) Al -A42
0.03%, 87.5% :; 0.05%, 94.4% < 0.07%) and were considered to be “true negatives”. Two of the 4 patients with a breath test result in the grey zone underwent repeat endoscopy which showed them to be H. pylon’-negative in CLO, histology and culture of antral and corpus biopsies. They were therefore considered to have had a “false positive” breath test result. The other two still need to be endoscoped. Conclusion: In this first Dutch long term follow-up study the great majority of successfully treated ulcer patients have remained free of infection, thus demonstrating that H. pylon’ eradication is a.stable phenomenon over time. In the follow-up period of more then 2 years the recurrence rate of H. pykwi was found to be at most 2/72 (30/o), demonstrating that re-infections a:re rare in Holland. The 2 patients we consider positive, however, could have had a false-positive breath test result and they can only be classified properly after repeat endoscopy. No difference in recurrence rate was found in patients initially treated with 1 week versus 2 weeks of quadruple therapy. This observation substantiates the claim that 1 week of quadruple therapy is sufficient to cure ulcer patients. Only 4 days of quadruple therapy can effectively cure Helicobu&r pylon’ infkction. W.A. de Boer ‘, W.M.M. Driessen 2. Departments of Internal Medicine, ’ Sint Anna Ziekenhuis, Oss and ’ Sint Joseph Ziekenhuis, Veldhoven, Netherlands.
We have promoted 7 days of quadruple therapy (bismuth, tetracycline, metronidazole and omeprezole) as the optimal anti-Helicobaaer treatment because it is highly effective ( > 95% cure), is independent of metronidazole resistance, and has good patient tolerability. In this study we investigated whether treatment duration can be reduced to 4 days. Fiftyfour patients [34 men, 20 women, 21 (39%) smokers with functional dyspepsia or peptic ulcer disease ad biopsy-proven H. pylon’ infection] received omeprazole 20 mg b.d. days l-7, colloidal bismuth subcitrate 120 mg q.i.d. days 4-7, tetracycline 500 mg q.i.d. days 4-7 and metronidazole 500 mg days 4-7. At least .5 weeks after therapy a second endoscopy was performed in all with 10 biopsies: 2 (antrum) for CL0 test, 2 (antrum) for culture and 6 (2 antrum, 2 cardia, 2 corpus) for histology (Giemsa stain). A patient was considered cured if all 3 tests were negative. All patient,5 finished the treatment but two had a 14C-urea breath test instead of endoscopy to confirm cure. Side-effects did not interfere with compliance. 49/54 patients (91%, 95% confidence inlerval SO-97%) were cured of their H. pylon’ infection. In 43/54 patients pre-treatment metronidazole resistance was known; of these 38/40 (95%) with a metronidazole-sensitive strain and 1 of 3 with a metronidazole-resistant strain were cured. Conclusion: We found 4 days of quadruple therapy after omeprazole pretreatment to be a well-tolerated but above all effective treatment for H. pylon’ infection, especially in those carrying a me:tronidazole-sensitive strain. Our results need confirmation to allow recommendation, but for patients suffering from side-effects on the 7-day quadruple regimen it seems possible to interrupt treatment after 4 days. Moreover,
Al5
these data suggest that for 7-day quadruple therapy, comphante is less critical than for other regimens.
Effects of eradicating H. pylon’ on symptoms in non-ulcer dyspepsia patients. M.L. Verhulst, W.P.M. Hopman, J.B.M.J. Jansen. Department of Gastroenterology and Hepatology, University Hospital, Nijmegen, Netherlands. The effects of eradicating H. pylon (Hp) on symptoms in
patients with non-ulcer dyspepsia (NUD) remains unclear. Some studies have shown a decrease in symptom scores after eradicating Hp, whereas others did not find such a decrease. The follow-up period in most studies is unfortunately very short. We therefore studied the effects of eradicating Hp on upper abdominal complaints in NUD patients. Thirty-nine HP-positive, NUD patients (25M, 14F) were studied. Before, immediately after 1 month after and > 1 year after Hp eradication therapy, symptoms like epigastric pain, nausea vomiting, pyrosis, belching, bloating and bad smell were scored on a visual analog scale. One month after eradication therapy endoscopy was performed and biopsies for HP culture, CL0 test and histology were taken. One month after eradication therapy Hp was eradicated in 21 of 39 patients (54%). The overall symptom scores significantly (p < 0.001) decreased from 24*2 before therapy to 8+ 2 immediately after therapy to 11 + 1 at 1 month after therapy and to 11+2 at 1 year after therapy in patients where HP was eradicated. In patients where Hp was not eradicated the overall symptom scores also gradually decreased, from 24+3 to 18f4 immediately after therapy (p = 0.08), form 24+3 to 15k2 at 1 month after therapy (p < O.OOS),and from 24*3 to 13 &-3 at > 1 year after therapy (p < 0.001). The differences in symptom scores between the patients in whom Hp was eradicated and in whom Hp was not eradicated were only significant (p < 0.05) immediately after eradication therapy. Conclusions: This study demonstrates that symptoms related to NUD significantly decrease in response to eradication therapy for Hp, not only in patients where Hp was eradicated, but also in those where Hp was not eradicated. Symptom scores in patients where Hp was eradicated were only significantly better than symptom scores in patients in whom eradication therapy had failed, immediately after therapy. Thereafter, no differences between the two groups were observed during a follow-up period of more than 1 year.
Hekcobader pylon’ and non- Hehwbader pybi bacterial flora before and after eradication therapy for Helicobucrer pylori. D.
Jonkers ‘, P. Houben ‘, A. de Bruine ‘, E. Stobberingh 3, R. Stockbriigger ‘. Departments of I Gastroenterology, 2 Pathology, and 3 Microbiology, University Hospital, Maastricht, Netherlands. Eradication of H. pylori by gastric acid inhibition in com-
bination with antibiotics can result in overgrowth of non-H. pykwi bacterial flora. This may confound the detection of H.
pylori. To assessthe intragastric bacterial flora, in 18 patients treated with amoxycillin (2 weeks) and omeprazole (6 weeks),
A16
Abstracts/Netherlands
Journal
gastric juice was cultured and two biopsies each of duodenum. antrum and corpus were obtained before and at the end of eradication therapy for culture and for histology by modified Giemsa (MG) and immunohistochemistry (IMM) against H. pylon’, respectively. Numbers of patients with H. pylori-positive and non-H. pylon’ positive biopsies by each method are shown in the table. Culture showed a significant increase in amount of oral flora (p < 0.05) in gastric juice, duodenal, antral and body mucosa after therapy. After therapy with culture as standard, sensitivity and specificity of MG were 60.7 and 80.9%, and of IMM 80.3 and 89.4%, respectively. Specimen
Before therapy Culture IMM HP HP non-HP
G. juice * Corpus Antrum Duod.
1 15 15 14
0 3 7 2
13 16 10
After therapy MG HP 11 17 5
Culture IMM HPP HP non-HP
MG HP
0 9 7 1
5 6 2
11 13 13 15
9 6 0
* Mean pH gastric juice: 1.4 (n = 18) before and 5.1 (n = 17) after eradication therapy, still on omeprazole 20 mg b.i.d. Conclusion: IMM is superior to MG for the detection of H. pylon’. Because of the possible presence of non-H. pylon’ flora after eradication therapy the use of IMM is recommended in this situation. Helicobacter pylori in gastric MALT lymphoma. I. Gisbertz lX3,
D. Jonkers ‘x2, J.W. Arends 3, R. Stockbriigger ‘, H.C. Schouten ‘. Departments of ’ Internal Medicine, ‘Microbiology and 3 Pathology, University Hospital, Maastricht, Netherlands.
Gastric mucosa-associated lymphoid tissue (MALT) tumours develop possibly in response to local infection by Helicobacter pylon’ (HP). We investigated the presence of Hp and non-HP intragastric bacterial flora in 26 patients with gastric MALT lymphoma, classified as low-grade (9 cases) or high-grade histology (17 cases). Serial sections were stained with haematoxylin-eosin, modified Giemsa, and immunohistochemically with a specific polyclonal antibody for Hp. Fourteen patients (54%) showed presence of Hp in the mucosa surrounding the tumour. In the tumour no presence of Hp was found. In 16 patients (61%), other bacteria (non-HP) were seen. The table shows the distribution of bacterial flora among low- and high-grade MALT lymphomas. The percentage of HP-positive cases in our study (54%) is lower than that reported in the literature (about 90%). This could be due to less specific staining methods, overestimating the presence of Hp or to the fact that those figures mainly represent low-grade MALT lymphomas. H. pylon’
Other bacteria
Low grade (n = 9) (mean age 58.5; 7 6,2? 1
6 (67%)
4 (44%)
High grade (n = 17) (mean age 61.9; 86,9?)
8 (47%)
12 (71%)
qf Medicine 48 (I9961 Al -A42 Conclusions: (1) Using a specific staining method for Hp, the prevalence of Hp in patients with gastric MALT lymphoma is probably not different from the normal population. (2) Hp is found in a similar frequency in low and high grade gastric MALT lymphomas. (3) Our results suggestthat non-Hip bacterial flora may play a role in the development of MALT. ca&4 status of Hehbacter
pylori in gastric MALT Iymphema.
D. de Jong ‘, H. Boot ‘, B.G. Taal’, W. van Dijk ‘, E. Kuipers 4, G. Pals ‘. Departments of ’ Pathology and ’ Gastroenterology, Antoni van Leeuwenhoek Ziekenhuis, Amsterdam; “Bacteriology, Sloteruaart Ziekenhuis, Amsterdam; 4 Gastroenterology and 5 Human Genetics, Free University, Amsterdam, Netherlands.
There is increasing evidence that persistent infection with Helicobacter pylon’ (HP) is a risk factor for development of
gastric adenocarcinoma as well as primary gastric non-Hodgkin’s lymphoma of mucosa-associated(MALT) type. Approximately 50% of HP isolates possess a gene, cagA, which encodes a high-molecular-weight protein of variable size that is highly associated with vacA expression. It has been shown that cagrl-positive strains are associated with enhanced acute inflammation and with peptic ulcer disease and therefore identify more aggressive strains. Also an increased risk for development of atrophic gastritis during long-term follow-up and a slightly increased risk for development of gastric cancer, especially of intestinal type, has been reported. In this study, we investigated the relation between cagA status and gastric MALT-NHL. Fifteen bacterial strains isolated from 10 patients with gastric MALT-NHL were analyzed using a cagA PCR assay. In 6 patients a cagrl-specific PCR-product was found. Four patients had a cad-negative strain. In 3 patients, multiple bacterial isolates, collected during follow-up, were analyzed. In all cases, consistent results were found (2 cagApos, 1 cagA-neg). As controls, 58 patients with chronic HP infection were analysed for serum antibodies to cagA using an ELISA assay. It has been shown that cagA status as determined by PCR and ELISA assays correlate to a very high extent. Due to infection with multiple strains, serum analysis may give somewhat higher cag,4-positive incidences. PCR analysis is more sensitive, however: 24/58 (41%) subjects were cagA-positive, 34/58 (59%) were cad-negative. During follow-up, 26 patients developed atrophic gastritis, of whom 60% were cag,4-positive;9/32 (30%) patients without atrophic gastritis were cagA-positive. Conclusions: These preliminary results indicate that similarly to gastric adenocarcinoma also gastric MALT-NHL is related to cagrl-positive HP strains. cagA-positive HP strains are reported to induce a significantly higher local and systemic immune reaction. The chronic local immune reaction can be recognized as induced MALT and is considered to harbour the precursor population of MALT-NHL. Helicobacter pylon’ eradication and gastric MALT lymphoma - early results. H. Boot ‘, D. de Jong ‘, P. van Heerde ‘, J.V.M. Burgers 3, B.G. Taal I. Departments of I Gastroenterology, 2 Pathology and 3 Radiotherapy, Netherlands Cancer Institute / Antoni van Leeuwenhoekhuis, Amsterdam, Netherlands.