Alimentary Pharmacology & Therapeutics Symposium Series最新文献

Summary

Background

Although resistance of Helicobacter pylori to metronidazole had been reported to be associated with mutations in the rdxA or the frxA gene, recent studies have indicated that they may contribute little to metronidazole resistance.

Aim

To clarify the roles of these genes in metronidazole resistance, we examined them in strains that were not eradicated by first-line eradication therapy.

Patients and methods

A total of 132 patients (92 males, 40 females, average age: 53.8 years old) who underwent upper gastrointestinal endoscopy after unsuccessful first-line H. pylori eradication were enrolled. Antibiotic susceptibility to metronidazole was investigated using the agar dilution method. The H. pylorirdxA and frxA genes were then sequenced.

Results

In the metronidazole-resistant strains, the sensitivity of detection of frameshift mutations in the rdxA gene was 44%. A significant association between the presence of frameshift mutations in the rdxA gene and resistance to metronidazole was observed. No significant association between frameshift mutations in the frxA gene and resistance to metronidazole was observed.

Conclusion

Mutation in the rdxA gene was sufficient, but not necessary to confer resistance to metronidazole in H. pylori. Mutation in the frxA gene was not necessary for resistance to metronidazole in H. pylori.

Summary

Aim

To systematically determine the usefulness of Helicobacter pylori IgG antibody titer decline as a predictor of treatment success after H. pylori eradication in large patient samples.

Patients and Methods

Serum samples from 258 H. pylori positive patients (52.8 yrs, 65% males) were retrospectively collected from five medical centers, and H. pylori titers were quantitatively determined by ELISA. Serial serum samples were collected at baseline and for up to 4.9 years after treatment. 169 patients underwent successful eradication while 89 remained infected. The median total observation period was 635 days (range, 51 to 1,800 days). Chronological changes in H. pylori titers were analyzed and compared between cured and infection persistent subjects.

Results

The proportion of infection persistent patients who developed negative H. pylori IgG antibody titers was below 5%. A receiver operating characteristic (ROC) curve for the confirmation of successful eradication according to the percent decline over baseline at each time-point showed that a 60% decline at 1 year or more after eradication treatment strongly correlated with successful eradication (sensitivity = 90% and specificity = 87%).

Conclusion

A 60% decline in H. pylori IgG titers (HEL-p kit) from baseline to one year or greater is a reliable predictor of successful H. pylori eradication.

Summary

Aim

To conduct a retrospective multicentre study at 31 medical centres in Japan, to investigate the association between the eradication of Helicobacter pylori and the development of new gastric cancer after endoscopic mucosal resection (EMR) for early gastric cancer.

Methods

Patients included those in whom early gastric cancer had been removed by EMR, and who had received follow-up endoscopic treatment. All patients underwent follow-up endoscopic treatment at least once a year after the initial EMR. The rate of new gastric cancer development was compared among those patients for whom H. pylori had been successfully eradicated and those with persistent H. pylori infection.

Results

The study included 2835 patients with a median follow-up period of 2 years (range 0.5–12 years). Helicobacter pylori was eradicated in 356 patients (13%). Metachronous gastric cancers developed in eight (2%) patients among those who had been successfully treated for H. pylori, compared with 129 patients (5%) among those with persistent H. pylori infection (P = 0.021; OR = 0.42; 95% CI = 0.20–0.86).

Conclusion

Although longer term, prospective randomized controlled trials are needed to better estimate the extent and sustainability of possible benefits, this study suggests that the eradication of H. pylori may help reduce the incidence of metachronous gastric cancer.

Summary

Background

Gastro-oesophageal flap valve (GEFV) grade correlated with endoscopic reflux oesophagitis (RE) prevalence.

Aim

To investigate relationships among gastro-oesophageal reflux disease (GERD) symptoms, RE and/or non-erosive reflux disease (NERD) and GEFV grades in subjects undergoing endoscopy.

Methods

We enrolled 1305 subjects from whom endoscopic results and the results of a self-administered questionnaire (QUEST) were available. Subjects were evaluated for GERD symptoms (QUEST score), GEFV grade, RE and gastric mucosal atrophy.

Results

Total GERD prevalence, including symptomatic GERD (QUEST score ≥ 4) and/or RE, was 27%. RE grade and prevalence increased with GEFV grade. QUEST scores and GEFV grades showed a positive correlation. NERD prevalence was 14% and increased with GEFV grade, but the relationship was weaker than that between RE and GEFV. Comparing RE-negative subjects by GEFV grade, GERD symptoms were noted in 10%, 19%, 36% and 52% with GEFV grades I, II, III and IV, respectively. Neither type of gastric mucosal atrophy correlated with GEFV grade.

Conclusions

Total GERD, NERD and RE prevalences increased with GEFV grade. Subjects with high GEFV grades often complain of GERD symptoms, even without RE. Our findings suggest that endoscopic GEFV evaluation provides a useful clinical index for diagnosing GERD.

Summary

Background

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a transcriptional factor induced by ischaemic crisis in many tissues. Vascular endothelial growth factor (VEGF) is an important growth factor that plays a major role in angiogenesis.

Aim

We examined the aetiology and pathophysiology of human ischaemic colitis and ulcerative colitis from the viewpoint of the expression of these two ischaemic factors.

Methods

Thirty-two patients with ischaemic colitis, 16 with ulcerative colitis and 25 normal controls underwent colonoscopy. Biopsy samples were taken from a colitis lesion and a normal region in the same patient. In the normal controls, four biopsy samples were obtained from each subject. Biopsy samples were subjected to real-time polymerase chain reaction.

Results

Hypoxia-inducible factor and VEGF were overexpressed in ischaemic colitis lesions and quickly decreased to normal levels in the healing phase. In contrast, HIF but not VEGF was overexpressed in active ulcerative colitis lesions. In the remission phase of ulcerative colitis, VEGF decreased to low levels, although HIF was continuously overexpressed.

Conclusions

Overexpression of HIF and VEGF contribute to the tolerance of ischaemia in patients with active ischaemic colitis. The inconsistency in their expression might be associated with the chronic intestinal damage characteristic of ulcerative colitis.

Summary

Background

The only authorized second-line Helicobacter pylori regimen in Japan is proton pump inhibitor + amoxycillin + clarithromycin. However, it has been reported that this second-line regimen is not effective. In this study, we evaluated the efficacy of dual and triple eradication therapies using rabeprazole as second-line H. pylori eradication regimens.

Aim

To evaluate the efficacy of dual and triple eradication therapies using rabeprazole as second-line H. pylori eradication therapy.

Methods

Sixty-two H. pylori-positive patients with first-line eradication failure were randomly assigned to two groups. The RAM group was administered rabeprazole 20 mg + amoxycillin 1500 mg + metronidazole 500 mg daily for 1 week. The RA group was administered rabeprazole 40 mg + amoxycillin 2000 mg daily for 2 weeks. Eradication of H. pylori infection was determined by ¹³C-urea breath testing at 8 weeks after completion of treatment. Prior to treatment, amoxycillin, clarithromycin and metronidazole susceptibility, and CYP2C19 phenotype status were determined.

Results

Eradication rates for the RAM and RA groups were 97% and 74%, respectively. Eradication rates were not influenced by CYP2C19 phenotype in either group. Eradication rates for clarithromycin-resistant patients were 100% in the RAM group and 77% in the RA group.

Conclusions

One week with RAM therapy and 2 weeks with RA therapy were effective as second-line eradication therapy for H. pylori infection; moreover, RAM was more effective than RA therapy.

Summary

Background

Atrophic and inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia. However, detailed data regarding the correlation between the severity of these changes and the symptoms of functional dyspepsia are not available.

Aim

To evaluate grading scales of gastric atrophy and inflammation, severity of clinical symptoms, and gastric emptying in patients with functional dyspepsia.

Methods

Ninety-three patients with dyspepsia were enrolled. The severity of gastric atrophy was graded through serological and histological examination, and gastric inflammation was evaluated histologically. Clinical symptoms were evaluated on the Gastrointestinal Symptoms Rating Scale, including subscales for abdominal pain, acid reflux, diarrhoea, indigestion and constipation. Gastric emptying half-time was measured using a radioisotope technique.

Results

Helicobacter pylori infection and gastric inflammation influenced neither clinical symptoms nor gastric emptying time. However, a correlation was observed between gastric atrophy as graded by serological examination and indigestion (R = 0.31, P = 0.01). Histological examination also showed a correlation between gastric atrophy and abdominal pain and indigestion (R = 0.31, P = 0.04 and R = 0.35, P = 0.02 respectively).

Conclusion

Gastric atrophy associated with H. pylori infection may be partly responsible for the clinical symptoms experienced by patients with functional dyspepsia.