Akifumi Tanaka

Relationship between eradication therapy and clarithromycin-resistant Helicobacter pylori in Japan

Background: Screening patients with columnar metaplasia of the oesophagus for adenocarcinoma is controversial owing to the low cancer incidence and diverging opinions as to whether screening improves the prognosis of these patients. Our aim was to evaluate a screening program for adenocarcinoma in patients with columnar metaplasia in the oesophagus, with focus on cancer incidence and costs. Methods: One hundred and ninety-nine patients with columnar metaplasia of the oesophagus were identified through an endoscopy database, and the original patient records were reviewed. Results: The patients were followed up for 797 years in total and during this time were subjected to 1071 upper gastrointestinal endoscopies. During the screening period 5 patients presented with adenocarcinoma; thus the cancer-incidence was 1 in 159 patient-years. The cost of detecting one cancer was 294,950 SEK (US

Efficacy of Clostridium butyricum preparation concomitantly with Helicobacter pylori eradication therapy in relation to changes in the intestinal microbiota

37,815). However, only four of the five patients were suitable for oesophagectomy, and of these, one patient turned out to have an advanced cancer. All patients developing cancer had columnar metaplasia of the oesophagus longer than 3 cm and specialized columnar epithelium (intestinal metaplasia/Barrett oesophagus). Conclusions: Low cancer incidence, high costs, and the doubtful prognosis for the patients with identified cancer question the benefits and cost-effectiveness of cancer screening among patients with columnar metaplasia in the oesophagus.Since clarithromycin is expected to be widely used to treat Helicobacter pylori infection in the near future, it is important to investigate the relationship between resistance to clarithromycin and the regimens of eradication therapy. We investigated: (1) the usefulness of susceptibility tests prior to eradication therapy, and (2) the rate of acquisition of H. pylori resistance to clarithromycin after treatment failure. Drug susceptibility tests to clarithromycin and amoxicillin were conducted by Dry Plate Test or E-test. The subjects in the first part of this study included 112 patients with H. pylori infection who received triple therapy with various combinations of drugs, including clarithromycin. The eradication rate in patients with clarithromycin-susceptible H. pylori was significantly higher than that in patients with clarithromycin-resistant H. pylori. The second part of this study included 21 patients in whom H. pylori was not eradicated by triple therapy and 12 patients in whom H. pylori was not eradicated with dual therapy including clarithromycin. Of the 33 patients showing non-eradication, 90.9% of those treated with dual therapy and 35.7% of those treated with triple therapy acquired secondary resistance of H. pylori to clarithromycin. We conclude that it is important to conduct drug susceptibility tests prior to treatment of H. pylori infection. Since the incidence of acquiring clarithromycin resistance was significantly higher in the patients showing non-eradication, it is important to choose a regimen with a higher eradication rate, such as triple therapy.Abstract: Since clarithromycin is expected to be widely used to treat Helicobacter pylori infection in the near future, it is important to investigate the relationship between resistance to clarithromycin and the regimens of eradication therapy. We investigated: (1) the usefulness of susceptibility tests prior to eradication therapy, and (2) the rate of acquisition of H. pylori resistance to clarithromycin after treatment failure. Drug susceptibility tests to clarithromycin and amoxicillin were conducted by Dry Plate Test or E-test. The subjects in the first part of this study included 112 patients with H. pylori infection who received triple therapy with various combinations of drugs, including clarithromycin. The eradication rate in patients with clarithromycin-susceptible H. pylori was significantly higher than that in patients with clarithromycin-resistant H. pylori. The second part of this study included 21 patients in whom H. pylori was not eradicated by triple therapy and 12 patients in whom H. pylori was not eradicated with dual therapy including clarithromycin. Of the 33 patients showing non-eradication, 90.9% of those treated with dual therapy and 35.7% of those treated with triple therapy acquired secondary resistance of H. pylori to clarithromycin. We conclude that it is important to conduct drug susceptibility tests prior to treatment of H. pylori infection. Since the incidence of acquiring clarithromycin resistance was significantly higher in the patients showing non-eradication, it is important to choose a regimen with a higher eradication rate, such as triple therapy.BACKGROUND Screening patients with columnar metaplasia of the oesophagus for adenocarcinoma is controversial owing to the low cancer incidence and diverging opinions as to whether screening improves the prognosis of these patients. Our aim was to evaluate a screening program for adenocarcinoma in patients with columnar metaplasia in the oesophagus, with focus on cancer incidence and costs. METHODS One hundred and ninety-nine patients with columnar metaplasia of the oesophagus were identified through an endoscopy database, and the original patient records were reviewed. RESULTS The patients were followed up for 797 years in total and during this time were subjected to 1071 upper gastrointestinal endoscopies. During the screening period 5 patients presented with adenocarcinoma; thus the cancer-incidence was 1 in 159 patient-years. The cost of detecting one cancer was 294,950 SEK (US

Evaluation of Helicobacter pylori stool antigen test before and after eradication therapy

37,815). However, only four of the five patients were suitable for oesophagectomy, and of these, one patient turned out to have an advanced cancer. All patients developing cancer had columnar metaplasia of the oesophagus longer than 3 cm and specialized columnar epithelium (intestinal metaplasia/Barrett oesophagus). CONCLUSIONS Low cancer incidence, high costs, and the doubtful prognosis for the patients with identified cancer question the benefits and cost-effectiveness of cancer screening among patients with columnar metaplasia in the oesophagus.

Amoxicillin resistance in Helicobacter pylori: studies from Tokyo, Japan from 1985 to 2003.

Antibiotic associated diarrhea due to human intestinal microbiota abnormalities is a side effect of H. pylori eradication therapy. We examined intestinal microbiota changes during H. pylori eradication therapy and the preventive effect of CBM588 as a probiotic agent. Nineteen patients with gastro‐duodenal ulcer were randomly divided into three groups: group A (without probiotics), group B (with regular doses of CBM588) and group C (with double doses of CBM588). The incidence of diarrhea and soft stools during H. pylori eradication therapy was 43% in group A and 14% in group B, while none of the patients in group C reported diarrhea or soft stools. Both bacterial counts and detection rates of bifidobacteria and/or obligate anaerobe were decreased by eradication therapy. However, bacterial counts of obligate anaerobes in group C were significantly higher than in group A (P < 0.05). Additionally, during eradication therapy C. difficile toxin A was detected in both group A and group B but not in group C.

Helicobacter pylori and acetylsalicylic acid synergistically accelerate apoptosis via Fas antigen pathway in rabbit gastric epithelial cells.

Background and Aim: The Helicobacter pylori stool antigen (HpSA) test is useful for initial diagnosis of H. pylori infection, but there is disagreement regarding its diagnostic accuracy after eradication therapy. The aim of the present study was to evaluate the diagnostic accuracy of the HpSA test before and after eradication therapy.

Alterations in gastric mucous cell kinetics. Part of the defense system against H. pylori infection in the regenerating zone

Background.  Previous reports revealed no resistant strains of amoxicillin (AMPC), which is usually used in eradication therapy for H. pylori infection. However, the frequency and evolution of natural AMPC‐resistant strains in the Japanese population remains unknown.

Detection of mixed clarithromycin-resistant and -susceptible Helicobacter pylori using nested PCR and direct sequencing of DNA extracted from faeces

The mechanism for gastric epithelial cellular apoptosis by both H. pylori and NSAIDs remains unknown. Normal gastric epithelial cells, collected from rabbit stomach, were cultured with viable H. pylori and/or an acetylsalicylic acid for 24 hr as an in vitro model of gastric epithelial cell injury. The Fas antigen expression rate in the gastric epithelial cells was measured using a FACScan. In group E, in which H. pylori inoculation of epithelial cells was followed by treatment with an NSAID, the rate of Fas antigen expression was significantly higher than the rate observed after treatment with either H. pylori or NSAID alone. Despite the fact that drug treatment alone did not significantly increase the Fas expression rate vs control cells. The results suggest that H. pylori and NSAID induce gastric cell injury as apoptosis via the Fas antigen pathway in a synergistic manner and that this effect is particularly strong when NSAID treatment follows H. pylori infection.

Lactobacillus reuteri tablets suppress Helicobacter pylori infection--a double-blind randomised placebo-controlled cross-over clinical study.

Background: Gastric mucosa has two types of mucous cells: surface mucous cells (SMCs) and gland mucous cells (GMCs). Hdicobacter pylori (li. pyIori) do not attach to GMCs and mucins from GMCs inhibit the movement of li, pylori in the gastric mucous gel layer. H. pylon increase the cell kinetics ot gastric epithelial cells. AIM: To examine the effect of li. IEvlori intection on gastric epithelial cell kinetics from the viewpoint of the phenotype of gastric mucous ceils. Methods: Gastric mucosal biopsy specimens obtained from 10 nonintectad volunteers and 20 H, pylori infected patients before and after eradication were used. Formalin-fixed and paraffin-embedded tissue sections were examined by a sequential staining consisting ot immunoalkaline phosphatase method for Ki67, immunopemxidase method with monoclonal antibody HIK1083, and histochemical staining for SMCs (periodic acid oxidation-thionine Schiff reaction: PA-TS), Ki-67 labeling indices (Lls) and phenotype of proliferating gastric mucous cells were analyzed. Results: SMCs, GMCs and proliferating cells were simultaneously visualized in histological specimens; SMCs were stained blue with PA-TS, GMCs were stained red with liIK1083, and nuclei of proliferating cells stained brown with Ki-67. Proliferating SMCs were distributed in lower part of gastric foveola and proliferating GMCs were localized in the lower part ot gastric lm, eola around the generating zone. Ki-67 LIs were higher in H. pylori infected patmnts (0.15 in the corpus and 0,21 in the antrum) than in vohinteers (0.06 and 0.11) (p<0.001). Ratios of Ki-67 LIs of GMC to those of SMC (GMC/SMC ratio) were higher in H. pylori infected patients (0.18 in the corpus and 0.26 in the antrum) than in volunteers (0.08 and 0.08) (p<0.05). After the eradicanon of H. pylonS, the increased Ki-67 Lls and the GMC/SMC ratio in gastric mucosa of H. pyloriintected patterns decreased to ahnost normal levels. Conclusion: H. pylori increased cell kinetics of gastric mucous cells and increased the GMC/SMC ratio. The increased number of GMCs in the gastric generating zone may act as part of the defense system against H. pylori intectinn in the generating zone