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P Sipponen

Publications and source records attributed to P Sipponen.

At least 55 records · Page 3Linked to original sources
PubMed2000

Significant increase in antigastric autoantibodies in a long-term follow-up study of H. pylori gastritis.

In 30% of H. pylori-infected patients a certain type of antigastric autoantibodies, reacting against canalicular structures within human parietal cells, is detectable. Furthermore, it has been shown that these autoantibodies are correlated with atrophy of the mucosa in the corpus. The aim of this study was to analyse the prevalence of these anticanalicular autoantibodies (ACAB) and their significance for development of gastric mucosa atrophy in a 12-year follow-up period. Gastric biopsy specimens from 62 persons in Saaremaa Island, Estonia, were collected in 1997 and assessed independently by two pathologists in accordance with the updated Sydney system. The sera of these persons were immunohistochemically screened for ACAB and for classic parietal cell antibodies (PCA). In addition, for 37 of the 62 persons, gastric biopsies and sera collected 12 years earlier (1985) were investigated in an analogous manner. ACAB increased significantly, from 8 out of 37 in 1985 to 17 out of 37 in 1997 (P=0.004; McNemar test). In 1997 a significant correlation existed between the presence of ACAB and corpus mucosa atrophy (19 out of 30 versus 10 out of 32 without atrophy; P=0.01; odds ratio (OR)=3.8, 95% CI 1.4-10.6). However, no correlation was found between ACAB and development of atrophy in the period from 1985 to 1997. All 37 persons were PCA negative in 1985, whereas in 1997, 2 turned out to be PCA positive. ACAB increased significantly with duration of H. pylori gastritis. The correlation between ACAB and presence of gastric corpus atrophy was confirmed. However, it is possible that ACAB are the consequence of and not a causative factor in gastric mucosa atrophy, insofar as the association of ACAB with progression of corpus atrophy was not significant.

Aged↗
PubMed2000

Gastritis and gastric cancer. Western countries.

Helicobacter pylori infection is the cause of chronic gastritis that progresses to atrophic gastritis over years and decades in more than half of affected individuals. H. pylori gastritis and, particularly, subsequent atrophic gastritis increase the risk for gastric cancer on multifactorial basis. Largely unknown cascades of manifold reactions result in gene errors of epithelial cells in gastric and atrophic stomach, which raise the likelihood of gastric neoplasias and cancer among people infected by H. pylori. The prevalences and incidences of gastric cancer and H. pylori are similarly decreased during the past decades in western countries, supporting the view that H. pylori infection is a key event and a trigger of the phenomena that result in cancer in some of the infected subjects.

Carcinoma↗
PubMed2000

Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland)

BACKGROUND: Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and beta-carotene might be associated with reduced risk of colorectal cancer. METHODS: We tested the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled trial among 29,133 50-69-year-old male cigarette smokers. Participants were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models. RESULTS: Colorectal cancer incidence was somewhat lower in the alpha-tocopherol arm compared to the no alpha-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.55-1.09; log-rank test p = 0.15). Beta-carotene had no effect on colorectal cancer incidence (RR = 1.05, 95% CI 0.75-1.47; log-rank test p = 0.78). There was no interaction between the two substances. CONCLUSION: Our study found no evidence of a beneficial or harmful effect for beta-carotene in colorectal cancer in older male smokers, but does provide suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk.

Aged↗
PubMed2000

Cure of Helicobacter pylori infection after failed primary treatment: one-center results from 120 patients.

BACKGROUND: Treatment with a proton pump inhibitor (PPI) and antimicrobials cures Helicobacter pylori infection in about 90% of patients. This is a retrospective overview of our studies aiming to cure the infection in all compliant patients with failed initial therapy. METHODS: We retreated 120 (19% of 644) H. pylori-infected patients whose initial therapy had failed. The retreatments included (i) triple therapy (TT): colloidal bismuth subcitrate, metronidazole, amoxicillin (or tetracycline); (ii) quadruple therapy (QT): TT and a PPI; or (iii) high doses of both a PPI and clarithromycin combined with a further 1-3 individually selected antimicrobials. The eradication results were determined after 6-12 months. RESULTS: The 1st retreatment was successful in 70 of 120 patients. The 2nd retreatment cured 25 of the remaining 42 patients, the 3rd 13 of 17, and the 4th the last 4 patients. The cumulative eradication rate (ITT) was 93% (95% CI: 88.9%-97.9%; 8 patients withdrew after a failed 1st retreatment) and the rate was 100% in the remaining 112 patients who accepted several retreatments. The 1st retreatment with TT cured 23% (95% CI: 12%-34%) of 57 patients and QT 85% (95% CI: 74%-96%) of 41 patients who had initially undergone a failed metronidazole-based treatment. All retreatments were well tolerated. CONCLUSIONS: In this study, high doses of a PPI and clarithromycin combined with 1-3 antimicrobials according to susceptibility data proved to be the best drug combination in the cure of H. pylori infection after failed primary treatment. Giving imidazole- and bismuth-based QT (without clarithromycin) as the first-line treatment of H. pylori infection ensures that the number of failures remains low.

Anti-Bacterial Agents↗
PubMed2000

Implications of serum pepsinogen I in early endoscopic diagnosis of gastric cancer and dysplasia. Helsinki Gastritis Study Group.

BACKGROUND AND AIMS: The risk of gastric cancer (GCA) is increased in atrophic gastritis. A low serum pepsinogen group I (SPGI) level is a good serologic indicator of atrophic gastritis of the gastric corpus and fundus, and can be used for diagnosis of subjects with atrophic gastritis and of increased risk for GCA. The present study was undertaken to investigate whether SPGI assay and a diagnostic gastroscopy could enable the diagnosis of GCA at an early stage. MATERIAL AND METHODS: The study was carried out as part of the Alpha-Tocopherol, Beta-Carotene Cancer prevention study (ATBC study) in Finland, in which 22,436 male smokers aged 50-69 years were screened by SPGI. Low SPGI levels (< 25 microg/l) were found in 2196 (9.8%) men. Upper GI endoscopy (gastroscopy) was performed in 1344 men (61%) and 78% of these had moderate or severe atrophic corpus gastritis in endoscopic biopsies. A control series of 136 men from the ATBC study cohort with abdominal symptoms, but with SPGI > or = 50 microg/l were similarly endoscopied, and 2.2% of these had corpus atrophy. RESULTS: Neoplastic alterations were found in 63 (4.7%; 95% CI: 3.6%-5.8%) of the 1344 endoscopied men with low SPGI levels. Of these, 42 were definite dysplasias of low grade, 7 dysplasias of high grade, 11 invasive carcinomas, of which 7 were 'early' cancers, and 3 carcinoid tumors. In the control series, 1 man (0.7%) of the 136 men had a definite low-grade dysplasia. Thus, 18 (1.3%; 95% CI 0.7%-2.0%) cases with 'severe' neoplastic lesions (4 advanced cancers, 7 early cancers and 7 dysplasias of high grade) were found in the low SPGI group, but there were none in the control group. All four patients with advanced cancer died from the malignancy within 5 years (mean survival time 2.5 years), whereas surgical treatment in all those with early cancer or high-grade dysplasia was curative. One of the seven patients with early cancer and two of the seven with high-grade dysplasia died within 5 years, but none died from the gastric cancer. Thus, curative treatment was given to 14 of 18 men in whom a malignant lesion was found in gastroscopy. This is about 15% of all gastric cancer cases (92 cases) which were diagnosed within 5 years after SPGI screening in the 22,436 men. Among the gastric cancer cases of the main ATBC study, the 5-year survival rate was 33% (85% of the non-survivors died from gastric cancer). CONCLUSIONS: We conclude that assay of SPGI followed by endoscopy is an approach which can enable the early diagnosis of gastric cancer at a curable stage.

Aged↗
PubMed2000

Evaluation of blood tests to predict normal gastric mucosa.

BACKGROUND: To determine the accuracy of blood tests in predicting normal gastric mucosa confirmed by histological examination of gastric biopsy specimens. METHODS: In total, 207 consecutive patients referred for upper endoscopy were included. Two biopsy specimens each from the antrum and corpus were assessed histologically for the presence of Helicobacter pylori, gastritis, and atrophy. Serum samples were studied for H. pylori antibodies by enzyme immunoassay (Pyloriset EIA-G and EIA-A) and by a rapid latex agglutination test (Pyloriset Dry); pepsinogen I was measured by an immunoenzymometric assay (Gastroset PGI), gastrin by radioimmunoassay, and parietal cell antibodies by indirect immunofluorescence. RESULTS: In 101 (49%) of 207 patients, the gastric mucosa on histologic examination was normal. In the 63 patients aged 45 years or less, H. pylori IgG serology was negative in all 47 patients with normal gastric mucosa and none had low serum pepsinogen I levels. Among 144 patients over age 45 years, 72 had negative H. pylori IgG serology. Combining the serum pepsinogen I assay with the results of H. pylori IgG serology, 12 patients with normal serology but low serum pepsinogen I were found. Thus, 60 patients, 52 of whom showed normal gastric histology, had normal IgG serology and serum pepsinogen 1. In the remaining eight patients with normal blood tests, the histologic changes were very mild. CONCLUSIONS: Although negative H. pylori IgG serology alone in younger patients, and in combination with normal serum pepsinogen I levels in older patients, reliably predicted the presence of normal gastric mucosa, gastroscopy is still recommended for patients over 45 years.

Adult↗
PubMed2000

Diagnosis of Helicobacter pylori infection in patients with atrophic gastritis: comparison of histology, 13C-urea breath test, and serology.

BACKGROUND: Atrophic gastritis, a risk factor for gastric cancer, is a late consequence of Helicobacter pylori infection in approximately one-third of the infected patients. It has been suggested that gastric cancer would develop less frequently if H. pylori were eradicated. However, the prevalence of H. pylori infection may be underestimated in patients with atrophic gastritis and intestinal metaplasia if only biopsy-based diagnostic methods are used. METHODS: We compared histology, 13C-urea breath test (13C-UBT), and serology in H. pylori diagnostics in 50 male patients with atrophic corpus gastritis. RESULTS: H. pylori was detected in 15 (30%) patients by histology and in 14 (28%) by 13C-UBT, whereas increased serum antibody levels indicating H. pylori infection were found in 41 (82%) patients (P < 0.0001 between serology and both histology and 13C-UBT). H. pylori infection was associated with atrophic corpus gastritis in 84% of the present patients (in one patient with normal antibody titres H. pylori was defined histologically). CONCLUSIONS: H. pylori infection would have been missed in most patients with atrophic gastritis without the analysis of H. pylori antibodies. Therefore, in patients with atrophic gastritis, the use of serology is encouraged in diagnosing H. pylori infection.

Aged↗
PubMed2000

Classical Barrett esophagus contrasted with Barrett-type epithelium at normal-appearing esophagogastric junction. Central Finland Endoscopy Study Group.

BACKGROUND: Incomplete intestinal metaplasia or specialized columnar epithelium (SCE) is the histologic hallmark of Barrett esophagus (BE), but it may also occur at a normal-appearing gastroesophageal junction without BE. We studied whether differences occur between BE patients and those with SCE at the squamocolumnar junction but without BE (abbreviated JSCE), in terms of endoscopic and histologic signs of gastroesophageal reflux disease (GERD) and Helicobacter pylori gastritis. METHODS: A total of 1059 consecutive patients referred for endoscopy in one hospital district in Finland were enrolled in the study. Biopsy specimens (at least two from each site) were obtained from the gastric antrum and the corpus of the stomach and from the esophagogastric junction and distal esophagus. RESULTS: Classical BE was detected in 25 (2%) and JSCE in 99 (9%) patients. Dysplasia in the metaplastic mucosa was observed in six BE patients but in none of the JSCE patients (P < 0.001). In multivariate analysis the independent risk factors for BE were endoscopic erosive esophagitis (odds ratio (OR), 6.08; 95% confidence interval (CI), 2.50-14.82), male sex (OR, 3.02; 95% CI, 1.20-7.65), and age (OR, 1.02 per year; 95% CI, 1.00-1.06). The independent risk factors for JSCE were endoscopic erosive esophagitis (OR, 1.88; 95% CI, 1.08-3.29) and age (OR, 1.03; 95% CI, 1.02-1.05) but not H. pylori infection (OR, 1.57; 95% CI, 0.83-2.97) or chronic gastritis (OR, 0.88; 95% CI, 0.44-1.75). In univariate analysis, however, JSCE was associated with antral-predominant atrophic gastritis (77% H. pylori-positive). Unlike in JSCE patients, male sex strongly predominated among BE patients (P = 0.01). The mean ages of BE and JSCE patients did not differ. CONCLUSIONS: Both BE and JSCE without BE increase in prevalence with age, and both associate with endoscopic erosive esophagitis but not with H. pylori gastritis. However, because of the marked sex disparity, JSCE cannot be a direct precursor of BE, and some factors other than GERD alone also play a role in the pathogenesis of BE. Compared with BE, dysplasia is a rare finding in JSCE, and endoscopic surveillance with biopsy specimens from JSCE patients without dysplasia is not recommended.

Barrett Esophagus↗
PubMed2000

Gastric dysplasia: the Padova international classification.

A worldwide-accepted histologic, classification of the gastric carcinomatous and precancerous lesions is a prerequisite for a consistent recording of epidemiologic data and for both developing and evaluating primary and secondary preventive efforts. Different nomenclatures have been proposed for gastric precancerous lesions in eastern countries and in Japan. This article presents a classification of gastric precancerous lesions resulting from an international consensus conference involving pathologists of different countries. Five main diagnostic categories are identified. To allow comparisons with the nomenclature proposed by the Japanese Research Society for Gastric Cancer, each category was also assigned a numeric identification: 1 = normal, 2 = indefinite for dysplasia, 3 = noninvasive neoplasia, 4 = suspicious for invasive cancer, and 5 = cancer. The interobserver reproducibility of the histologic classification was tested in a series of 46 cases. By collapsing benign alterations (categories 1+2) versus noninvasive neoplasia (category 3) versus suspicious for invasive cancer and fully appearing carcinomatous lesions (categories 4+5), the general agreement value was 77.7%, whereas kappa coefficient was 0.63. By examining gastric precancerous lesions from diverse populations, the authors agreed that the gastric precancerous process is universal and the differences in nomenclatures are merely semantics. The international Padova classification of the gastric precancerous lesions is submitted to the attention of the international scientific community, which is invited to test and to improve on it.

Adenocarcinoma↗
PubMed2000

Atrophic gastritis and Helicobacter pylori infection in outpatients referred for gastroscopy.

BACKGROUND: Atrophic gastritis has been shown to be one of the long term sequelae of Helicobacter pylori infection. AIMS: To determine the prevalence of atrophic gastritis in outpatients, to study the accuracy of serological methods for revealing atrophy, and to define the association of H pylori infection with atrophic gastritis in these patients. PATIENTS/METHODS: A total of 207 consecutive outpatients referred for gastroscopy were included. Biopsy specimens from the antrum and corpus were assessed histologically according to the Sydney system. Serum samples were studied for H pylori IgG and IgA antibodies by enzyme immunoassay, CagA antibodies by immunoblot, pepsinogen I by an immunoenzymometric assay, gastrin by radioimmunoassay, and parietal cell antibodies by indirect immunofluorescence. RESULTS: Histological examination revealed atrophic gastritis in 52 (25%) of 207 patients. H pylori and CagA antibodies were strongly associated with atrophic antral gastritis but poorly associated with atrophic corpus gastritis. Low serum pepsinogen I was the most sensitive and specific indicator of moderate and severe atrophic corpus gastritis. All six patients with moderate atrophic corpus gastritis had H pylori infection but eight of 10 patients with severe atrophic corpus had increased parietal cell antibodies and nine had no signs of H pylori infection. CONCLUSIONS: Atrophic antral gastritis was strongly associated with CagA positive H pylori infection. Severe atrophic corpus gastritis was not determined by H pylori tests but low serum pepsinogen I, high gastrin, and parietal cell antibodies may be valuable in detecting these changes.

Adult↗
PubMed2000

The Vienna classification of gastrointestinal epithelial neoplasia.

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

Adenoma↗
PubMed2000

Gastroesophageal reflux disease: prevalence, clinical, endoscopic and histopathological findings in 1,128 consecutive patients referred for endoscopy due to dyspeptic and reflux symptoms.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) reportedly has increased in prevalence while Helicobacter pylori infection and peptic ulcer disease have been on the decrease. The aim of the present study was to examine the prevalence of GERD as well as the clinical, endoscopic and histologic variables that associate with GERD in patients referred for endoscopy. PATIENTS AND METHODS: The study population was drawn from 1,562 consecutive patients referred for endoscopy. The exclusion criteria were previous H. pylori eradication, gastric surgery, anemia and weight loss. Thus 1,128 patients were enrolled in the present study. RESULTS: Of the 1,128 patients, 199 (18%) were referred for endoscopy due to heartburn and/or regurgitation. GERD, defined as chronic (>6 months) heartburn and/or regurgitation with or without erosive esophagitis, Barrett's esophagus, esophageal ulcer or stricture, was detected in 248 (22%) patients. Of the 248 GERD patients, 81 (33%) had endoscopy-negative GERD, but of those aged <50 years (n = 67), 57 (85%) were endoscopy-negative. The overall incidence of GERD was 307 per 100,000 population/year and that of endoscopy-positive GERD 207/100,000/year. The positive and negative predictive values of heartburn and regurgitation for endoscopy-positive GERD were 0.37 (95% CI 0.31-0.44) and 0.90 (95% CI 0.88-0.92), respectively. Independent risk factors for GERD were male sex (OR 1.9, 95% CI 1.3-2.7), previous medication for upper gastrointestinal symptoms (OR 2.7, 95% CI 1.7-4.1), the use of nonsteroidal anti-inflammatory drugs (NSAIDs; OR 2.0, 95% CI 1.3-3. 0), histologic esophagitis (OR 2.2, 95% CI 1.5-3.2) and incomplete intestinal metaplasia at the gastroesophageal junction (OR 1.7, 95% CI 1.0-3.1). Chronic gastritis was protective against GERD (OR 0.7, 95% CI 0.5-0.9). No association was observed between GERD and H. pylori infection. The risk of patients aged <50 years (n = 407) of having major lesion (Barrett's esophagus, esophageal stricture, peptic ulcer, esophageal/gastric carcinoma) was significantly lower than that of patients aged >50 years (n = 721; OR 0.5, 95% CI 0.3-0. 9, p = 0.01). CONCLUSIONS: The correlation between reflux symptoms and endoscopy-positive GERD is poor and most GERD patients aged <50 years have endoscopy-negative GERD. The use of NSAIDs is a risk factor for GERD, whereas chronic gastritis, but not H. pylori infection, may protect against GERD. Incomplete intestinal metaplasia at the gastroesophageal junction is associated with GERD.

Adenocarcinoma↗
PubMed1999

The DU-MACH study: eradication of Helicobacter pylori and ulcer healing in patients with acute duodenal ulcer using omeprazole based triple therapy.

AIM: To investigate the efficacy of two omeprazole triple therapies for the eradication of Helicobacter pylori, ulcer healing and ulcer relapse during a 6-month treatment-free period in patients with active duodenal ulcer. METHODS: This was a double-blind, randomized study in 15 centres across Canada. Patients (n = 149) were randomized to omeprazole 20 mg once daily (O) or one of two 1-week b. d. eradication regimens: omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (OMC) or omeprazole 20 mg, amoxycillin 1000 mg and clarithromycin 500 mg (OAC). All patients were treated for three additional weeks with omeprazole 20 mg once daily. Ulcer healing was assessed by endoscopy after 4 weeks of study therapy. H. pylori eradication was determined by a 13C-urea breath test and histology, performed at pre-entry, at 4 weeks after the end of all therapy and at 6 months. RESULTS: The intention-to-treat (intention-to-treat) analysis contained 146 patients and the per protocol (per protocol) analysis, 114 patients. The eradication rates were (intention-to-treat/per protocol): OMC-85% and 92%, OAC-78% and 87% and O-0% (O). Ulcer healing (intention-to-treat) was greater than 90% in all groups. The differences in the eradication and relapse rates between O vs. OMC and O vs. OAC were statistically significant (all, P < 0.001). Treatment was well tolerated and compliance was high. CONCLUSION: The OMC and OAC 1-week treatment regimens are safe and effective for eradication, healing and the prevention of relapse in duodenal ulcer patients.

Acute Disease↗
PubMed1999

The GU-MACH study: the effect of 1-week omeprazole triple therapy on Helicobacter pylori infection in patients with gastric ulcer.

AIMS: To study the efficacy of omeprazole triple therapy in the eradication of Helicobacter pylori in patients with active gastric ulcer, and to assess healing and relapse of gastric ulcer. METHODS: A double-blind, randomized study was carried out in 18 centres in Germany, Hungary and Poland. Patients (n = 160) with gastric ulcer and a positive H. pylori screening test were randomized to a 7-day twice daily treatment with omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1000 mg (OAC) or omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg (OMC), or with omeprazole 20 mg once daily (O). After completion of this 1-week treatment, patients were treated with omeprazole until healing (maximum 12 weeks), and followed for 6 months. H. pylori was assessed by urea breath test (UBT) and histology. RESULTS: Eradication rates ITT were OAC 79% (95% CI: 65-90%), OMC 86% (95% CI: 73-94%) and O 4% (95% CI: 0-14%). Eradication rates PP were OAC 83% (95% CI: 68-93%), OMC 93% (95% CI: 80-98%) and O 3% (95% CI: 0-13%). Gastric ulcer relapses occurred in 5, 0 and 11 patients in the groups, respectively. CONCLUSIONS: The results from the study demonstrate that OMC and OAC 1-week regimens are safe and effective for eradication of H. pylori in gastric ulcer patients, and that ulcer relapse is infrequent after successful eradication.

Adult↗
PubMed1999

Efficacy of two different dosage regimens of omeprazole, amoxycillin and metronidazole for the cure of Helicobacter pylori infection.

BACKGROUND: While addition of metronidazole to the omeprazole-amoxycillin combination has been shown to be advantageous, the optimal dosage and drug distribution of the antimicrobials has not been sufficiently evaluated. AIM: To investigate the efficacy of two different regimens of omeprazole, amoxycillin and metronidazole for the cure of Helicobacter pylori infection. METHODS: Two hundred and fifty-five patients with H. pylori associated duodenal ulcers were randomly treated with either a 1-week regimen of omeprazole 20 mg b.d., amoxycillin 1000 mg b.d. and metronidazole 800 mg b.d. (OAM b.d.) or a combination of omeprazole 40 mg o.d., amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. (OAM t.d.s.). All patients subsequently received omeprazole 20 mg o.d. for an additional 3 weeks. H. pylori status was assessed by histology and 13C-UBT prior to treatment and 8 weeks after randomization. Additional biopsies were obtained for H. pylori culture to determine primary and secondary resistance to metronidazole by agar dilution. RESULTS: Two hundred and thirty-seven patients were included in the intention-to-treat analysis and 198 patients in the per protocol analysis. With intention-to-treat analysis, the cure rate was 77% after treatment with OAM b.d. (95% CI, 69%-85%) and 76% after OAM t. d.s. therapy (95% CI, 67%-83%). Ulcer healing (intention-to-treat analysis) was documented in 95% of patients in the OAM b.d. group (n=122) and in 97% of patients in the OAM t.d.s. group (n=115). Adverse events were reported in 26 (20%) and in 18 (14%) patients in the OAM b.d. and OAM t.d.s. groups, respectively. None resulted in discontinuation of treatment. Overall primary resistance of H. pylori against metronidazole was found in 22 of 116 strains (19%). CONCLUSIONS: The combination of omeprazole, amoxycillin and metronidazole achieves about an 80% cure rate of H. pylori infection even in active ulcers. The total daily dose, and the choice of twice or three times daily dosing does not seem critical with this regimen.

Aged↗
PubMed1999

Observer agreement on the grading of gastric atrophy.

AIMS: Assessment of lesser or doubtful degrees of gastric atrophy can be difficult, especially in the antrum, since well established criteria are lacking. At the Houston Working Party on Gastritis in 1994 a visual analogue scale was designed for the grading of histopathological parameters. This was done to promote uniformity in grading by acting as a reference. The purpose of the present study was to measure interobserver variation between pathologists familiar with the Houston visual analogue scale in a specifically selected set of biopsies from patients with lesser or doubtful degrees of atrophy. METHODS AND RESULTS: Thirty cases with biopsies of the antrum and corpus from a long-term follow-up study on Helicobacter pylori gastritis comprised the current study material. The cases were selected from that study because there had been uncertainty or disagreement on the presence of gastric atrophy. The study set of haematoxylin and eosin (H & E) slides was circulated amongst gastrointestinal pathologists familiar with the visual analogue scale who were unaware of the source of the study set nor had any other clinical information. Interobserver variability was analysed using kappa statistics. The overall agreement for the grade of atrophy in antral biopsies was 0.461; the kappa value was 0.18 (95% confidence limits 0.12-0.24), which is considered poor agreement. The kappa value was nevertheless statistically significant (P < 0. 01). The overall agreement on the grade of atrophy in the corpus biopsies was apparently good (0.833), but the kappa which adjusts for chance agreement was only moderate (0.48; 95% confidence limits 0.42-0.55; P < 0.001). CONCLUSION: The studied series comprised a self-selected sample in which there was doubt about the grade of atrophy and such a sample will produce lower kappa values than a random sample of gastric biopsies. The results nevertheless confirm that better guidelines and firm criteria are needed to properly diagnose and grade gastric atrophy. It is suggested that the use of two grades, low- and high-grade atrophy, akin to that in use for grading inflammatory bowel disorder (IBD)- associated dysplasia, could improve agreement. Furthermore optimal biopsy quality with full thickness mucosa and proper orientation appears important for grading gastric atrophy.

Atrophy↗
PubMed1999

An 18-year follow-up study of chronic gastritis and Helicobacter pylori association of CagA positivity with development of atrophy and activity of gastritis.

BACKGROUND: We wanted to evaluate the course of chronic gastritis and its association with Helicobacter pylori and CagA seropositivity in an adult sample from Saaremaa (Estonia) during an 18-year follow-up. METHODS: Seventy persons (31 men, 39 women; median age, 57.5 years) from a primary sample of 304 subjects endoscoped in 1979 were reinvestigated by endoscopy and biopsy in 1997. The state of the gastric mucosa and the presence of H. pylori in histologic sections from the antrum and corpus were assessed both in 1979 and 1997 in 66 subjects in accordance with the Sydney system, and H. pylori status in all 70 subjects was determined with the enzyme-linked immunosorbent assay (ELISA). Anti-CagA IgGs were determined with the ELISA, using the recombinant fragment of CagA. RESULTS: During an 18-year follow-up 11% of the subjects developed atrophy in the antrum, whereas 35% developed it in the corpus. Development of atrophy in the corpus and the appearance of intestinal metaplasia in the antrum were associated with increased activity of gastritis both in the initial and last follow-up biopsies. Anti-CagA positivity was found in 71% of H. pylori-seropositive persons (94% of subjects). There was a significant association between CagA positivity and the activity of gastritis, the presence of atrophy or damage to surface epithelial cells in the antrum and in corpus mucosal biopsy specimens at the last follow-up endoscopy. CONCLUSION: The CagA-positive strains of H. pylori enhance the development of atrophic gastritis compared with CagA-negative strains.

Antigens, Bacterial↗