Early gastric cancer: disease or pseudo-disease?
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Humans↗
Biomedical subjects
A T Axon
Publications and source records attributed to A T Axon.
Relevance of antibiotic sensitivities in predicting failure of omeprazole, clarithromycin, and tinidazole to eradicate Helicobacter pylori.
Omeprazole 20 mg once (o.d.) or twice daily (b.d.), clarithromycin 250 mg b.d., and tinidazole 500 mg b.d. for 7 days (OCT) is an effective regimen against Helicobacter pylori, but the effect of 5-nitroimidazole resistance is unclear. We aimed to evaluate this using the disc diffusion technique (Mast Diagnostics, Bootle, UK) and E-test (Cambridge Diagnostics Services, Cambridge, UK) to assess 5-nitroimidazole resistance. H. pylori was cultured from antral biopsies of infected patients, as determined by 13C-urea breath test (13C-UBT), histology, and/or rapid urease test. Patients were prescribed OCT and H. pylori eradication was assessed by 13C-UBT at least 4 weeks after completion of therapy. Antibiotic sensitivities to metronidazole and clarithromycin were evaluated by the disc diffusion method and by the measurement of minimum inhibitory concentration (MIC) using the E-test. One hundred and forty-one H. pylori-infected patients were enrolled in the study and the organism was successfully cultured from 119 patients (84%). The overall eradication rate was 125/141 (89%). OCT was successful in 62/69 (90%) patients harboring fully sensitive strains of H. pylori, compared with 42/45 (93%) of patients with strains that were resistant to metronidazole alone (P = 0.74, Fisher's exact test). MIC was assessed in 22 samples. Using a cut-off point of >32 microg/ml to define metronidazole resistance eradication rates were higher against sensitive (9/12; 75%) than resistant (3/10; 30%) strains (P = 0.08, Fisher's exact test). 5-Nitroimidazole resistance assessed by the disc diffusion technique is not helpful in predicting OCT failure, but the E-test may be of value.
Adult↗
Omeprazole is more effective than cimetidine in the prevention of recurrence of GERD-associated heartburn and the occurrence of underlying oesophagitis.
BACKGROUND: There is documentation of the long-term use of omeprazole 10 mg o.d. in patients with reflux oesophagitis but not in the large number of gastrooesophageal reflux disease (GERD) patients without oesophagitis. There is also a paucity of data on the long-term use of cimetidine in GERD patients. METHODS: One hundred and fifty-six patients (100 male) who previously had symptomatic non-ulcerative oesophagitis (81%) or symptoms without oesophagitis (19%), were recruited. All patients were in symptomatic remission following 4 weeks of omeprazole 20 mg o.d. or cimetidine 400 mg q.d.s. and, if required, a further 4 weeks of omeprazole 20 mg o.d. Patients were randomized to receive, double-blind, either omeprazole 10 mg o.m. (n = 77) or cimetidine 800 mg nocte (n = 79) for 24 weeks. RESULTS: A greater proportion of patients receiving omeprazole, compared with cimetidine, were in symptomatic remission after 12 (69 vs. 27%) and 24 weeks (60 vs. 24%) (each P < 0.0001). The median time to symptomatic relapse was longer for patients receiving omeprazole (169 vs. 15 days) (P = 0.0001). Of patients leaving the study in symptomatic remission, a greater proportion receiving omeprazole, compared with cimetidine, was free of oesophagitis (84 vs. 53%) (P < 0.05). CONCLUSION: Omeprazole 10 mg o.m. is more effective than cimetidine 800 mg nocte in the prevention of recurrence of GERD-associated heartburn and the occurrence of underlying oesophagitis.
Administration, Oral↗
The Leeds Dyspepsia Questionnaire: a valid tool for measuring the presence and severity of dyspepsia.
BACKGROUND: There is currently no validated questionnaire that assesses both the presence and severity of dyspepsia. AIM: To develop the Leeds Dyspepsia Questionnaire (LDQ) as a measure of the presence and severity of dyspepsia, and to assess the validity, reliability and responsiveness of this instrument. METHODS: Unselected patients attending either a hospital dyspepsia clinic or a general practice surgery were interviewed by a trained gastroenterologist or a general practitioner on the presence and severity of dyspepsia. This opinion was compared with the results of the nurse-administered LDQ. Test-retest reliability was assessed by the same research nurse re-administering the LDQ 4-7 days after the initial visit in a subgroup of hospital patients. In a further subgroup of patients one researcher interviewed the patients and a second researcher re-administered the LDQ within 30 min to evaluate inter-rater reliability. The responsiveness of the LDQ was measured by repeating it in patients with endoscopically proven peptic ulcer or oesophagitis 1 month after receiving appropriate therapy. RESULTS: The LDQ was administered to 99 general practice and 215 hospital patients. In the GP population 41/98 (42%) had dyspepsia according to the GP and the LDQ had a sensitivity of 80% (95% CI: 65-91%) and a specificity of 79% (95% CI: 66-89%). The weighted kappa statistic for the agreement between the LDQ and the clinician for the severity of dyspepsia was 0.58 in the GP population and 0.49 in hospital patients. The kappa statistic for test-retest reliability was 0.83 in 107 patients. The LDQ had excellent inter-rater reliability with a kappa statistic of 0.90 in 42 patients. The median LDQ score fell from 22.5 (range 9-36) to 4.5 (range 0-27) in 12 patients 1 month after receiving appropriate therapy (Wilcoxon signed rank test, P < 0.0001). CONCLUSION: The LDQ is a valid, reliable and responsive instrument for measuring the presence and severity of dyspepsia.
Adolescent↗
Flat adenomas in the United Kingdom: are treatable cancers being missed?
BACKGROUND AND STUDY AIMS: The recognized pathway for colorectal malignancies is the adenoma-carcinoma sequence. It is estimated that up to two-thirds of colorectal carcinomas arise from adenomatous polyps. In recent years, Japanese workers have suggested that early colorectal malignancies may arise as "flat" or "depressed" rather than as polypoid lesions. Such flat or depressed adenomas and adenocarcinomas have not been widely recognized in the West. A prospective study was carried out to search for flat and depressed adenomas in a British population, using Japanese colonoscopic techniques. PATIENTS AND METHODS: In this prospective study at a British centre, 210 consecutive patients attending for routine colonoscopy were examined for flat or depressed lesions. The examinations were carried out using Japanese techniques by an experienced Japanese endoscopist (T.F.). RESULTS: Overall, 68 adenomas were found, of which 40 (59%) were polypoid, 26 (38%) were flat, and two (3%) appeared depressed. The majority of the adenomas contained areas of mild or moderate dysplasia, but four were severely dysplastic. Two of these were large polypoid tubulovillous adenomas, the third was a 7-mm protruding polyp, and the fourth was a depressed adenoma 6 mm in diameter. Three Dukes' stage A adenocarcinomas were also found. Of these, one was a 20-mm polyp, one a 15-mm flat elevation of the mucosa with a central depression, and the third a 6-mm depression of the mucosa. Finally, four Dukes' B or more advanced adenocarcinomas were found. CONCLUSIONS: The polyp-carcinoma hypothesis prompts colonoscopists to search only for polypoid lesions when screening for malignancy. A significant proportion of early colorectal neoplasms may therefore be missed. European colonoscopists require training in the recognition of flat elevated and depressed lesions in order to detect colorectal malignancies in their early stages.
Adenocarcinoma↗
UK-Japan exchange programme: Japanese endoscopists in the general infirmary at Leeds.
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Endoscopy↗
Is there a rationale for eradication of Helicobacter pylori? Cost-benefit: the case for.
Screening and treating the community for Helicobacter pylori would have seemed inconceivable 5 years ago. This has now become a real possibility given that H. pylori is a major risk factor for gastric carcinoma. Screening should not be introduced, however, before the costs and benefits of the programme are established. It has been estimated that 1:30-1:60 of the UK population die from an H. pylori related disease. If treating H. pylori were to reduce premature mortality, then this would be a persuasive argument for a screening strategy. The financial costs of screening and treating H. pylori are significant but this would be partially offset by savings that would accrue from reducing dyspepsia in the community. Indeed, decision analysis models suggest H. pylori screening is cost-effective. The potential benefits are enormous and prospective randomised trials are urgently required to establish whether such a programme is worthwhile.
Breath Tests↗
Granulocyte apheresis in inflammatory bowel disease: possible mechanisms of effect.
We have studied the effects of granulocyte apheresis in 18 patients with ulcerative colitis and 6 with Crohn's disease who had failed to respond to conventional therapy. Patients were treated with weekly apheresis using a granulocyte removal column (GI, Otsuka Pharmaceutical Co., Ltd., London, U.K.). We found a mean reduction in circulating granulocytes of 1.29 x 10(9) cells/L with no significant alterations in red blood cell monocyte, total lymphocyte, absolute T-helper, or T-cytotoxic lymphocyte counts. There were no significant changes in complement levels or immunoglobulin subclasses. There was a significant increase in granulocyte adhesion and a reduction in L-selectin expression. The removal of granulocytes is unlikely to explain the effect of granulocytapheresis. The markedly increased expression of alpha(m) integrin/Mac-1 and low L-selectin expression alter the capability of granulocytes to migrate to sites of inflammation and may be responsible for the improvement observed in patients treated with granulocyte apheresis.
Adult↗
Reactive oxygen species activity and lipid peroxidation in Helicobacter pylori associated gastritis: relation to gastric mucosal ascorbic acid concentrations and effect of H pylori eradication.
BACKGROUND: Helicobacter pylori is an independent risk factor for gastric cancer, and this association may be due to the bacterium causing reactive oxygen species mediated damage to DNA in the gastric epithelium. High dietary ascorbic acid intake may protect against gastric cancer by scavenging reactive oxygen species. AIMS: To assess reactive oxygen species activity and damage in gastric mucosa in relation to gastric pathology and mucosal ascorbic acid level, and to determine the effect of H pylori eradication on these parameters. PATIENTS: Gastric biopsy specimens were obtained for analysis from 161 patients undergoing endoscopy for dyspepsia. METHODS: Reactive oxygen species activity and damage was assessed by luminol enhanced chemiluminescence and malondialdehyde equivalent estimation respectively. Ascorbic acid concentrations were measured using HPLC. RESULTS: Chemiluminescence and malondialdehyde levels in gastric mucosa were higher in patients with H pylori gastritis than in those with normal histology. Successful eradication of the bacterium led to decreases in both parameters four weeks after treatment was completed. Gastric mucosal ascorbic acid and total vitamin C concentrations were not related to mucosal histology, but correlated weakly with reactive oxygen species activity (chemiluminescence and malodialdehyde levels). CONCLUSIONS: Data suggest that reactive oxygen species play a pathological role in H pylori gastritis, but mucosal ascorbic acid is not depleted in this condition.
Adult↗
Treatment of Helicobacter pylori: future therapeutic and prophylactic perspectives.
Helicobacter is one of the most widespread, chronic infections in the world and causes a serious disease with a significant mortality. The organism is difficult to eradicate using antibiotic therapy and to date no vaccine is available for use in humans. The most successful treatments comprise acid suppression in combination with two antibiotics and a series of seven day courses will reliably cure around 85% of infected individuals. Further modifications of these regimens via the introduction of newer and more effective antibiotics and acid suppressants may enable the treatment to be simplified, made more effective and cause fewer side effects. However, the major challenge is to develop a specific monotherapy targeted against Helicobacter pylori. The H pylori genome has now been sequenced and this provides an opportunity both to identify specific targets for drug therapy, and to facilitate the identification and production of antigens that may be helpful in manufacturing a vaccine. This paper discusses the future of helicobacter therapy and vaccination.
Anti-Bacterial Agents↗
Clinical and histological associations of cagA and vacA genotypes in Helicobacter pylori gastritis.
AIMS: To determine the relation among the cytotoxin associated gene (cagA) and vacuolating cytotoxin gene (vacA) status of Helicobacter pylori isolates, the associated clinical diseases, and the severity and pattern of chronic gastritis. METHODS: Helicobacter pylori was cultured from gastric biopsies obtained from dyspeptic patients. DNA was extracted from the isolates and the cagA and vacA status determined by the polymerase chain reaction (PCR). The prevalence of the different cagA and vacA genotypes in three clinical groups, duodenal ulcer, gastric ulcer, and non-ulcer dyspepsia was compared. The histological features in sections from two antral and two corpus biopsies were graded by one blinded observer. The grades were compared with age and sex matched groups with different cagA and vacA genotypes, and with duodenal ulcers, or non-ulcer dyspepsia. RESULTS: Isolates from 161 patients were included. One hundred and nine (68%) harboured a cagA+ strain and 143 (89%) harboured a vacA s1 strain. The prevalence of cagA+ strains in duodenal ulcer patients (94%) was highly significantly greater than in those with non-ulcer dyspepsia (56%). However, of the patients infected with a cagA+ strain, almost equal numbers had non-ulcer dyspepsia or peptic ulceration. Chronic inflammation, polymorph activity, surface epithelial degeneration, atrophy, and intestinal metaplasia were all significantly more severe in the cagA+ than in the cagA- group, whereas only corpus epithelial degeneration was significantly more severe in the vacA s1 group compared with the vacA s2 group. Patients infected with cagA+ strains were almost four times more likely to have antral intestinal metaplasia than cagA- patients. An antral predominant gastritis was present in duodenal ulcer patients compared with matched non-ulcer dyspepsia patients, but this was not attributable to cagA or vacA status. CONCLUSIONS: Helicobacter pylori strains showing cagA positively and the vacA s1 genotype are associated with more severe gastritis but these virulence factors do not appear to determine the overall pattern. The pattern is closely linked to clinical disease. Therefore, it is likely that the nature of the disease complicating chronic infection is determined by host and environmental factors, while bacterial factors determine the magnitude of the risk of developing such disease.
Adolescent↗
Chemokine mRNA expression in gastric mucosa is associated with Helicobacter pylori cagA positivity and severity of gastritis.
AIM: To investigate the association between the quantity of gastric chemokine mRNA expression, severity of gastritis, and cagA positivity in Helicobacter pylori associated gastritis. METHODS: In 83 dyspeptic patients, antral and corpus biopsies were taken for semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and histological grading of gastritis. Gastritis was evaluated by visual analogue scales. Quantities of chemokine (IL-8, GRO alpha, ENA-78, RANTES, MCP-1) RT-PCR products were compared with G3PDH products. Each sample was also evaluated for the presence of cagA and ureA mRNA by RT-PCR. RESULTS: mRNA expression of all five chemokines was significantly greater in H pylori positive than in H pylori negative mucosa. In H pylori positive patients, in the antrum C-X-C chemokine mRNA expression was significantly greater in cagA positive patients than in cagA negative patients, but there were no significant differences in C-C chemokine mRNA expression. In H pylori positive patients, chemokine mRNA expression in the corpus was less than in the antrum. In contrast to the antrum, only GRO alpha mRNA expression was significantly greater in cagA positive infection. Polymorphonuclear cell infiltration was correlated with C-X-C chemokine mRNA expression. Significant correlations were also found between bacterial density and C-X-C chemokine mRNA expression. CONCLUSIONS: In H pylori infection, C-X-C chemokines may play a primary role in active gastritis. Infection with cagA positive H pylori induces greater gastric chemokine mRNA expression in the antral mucosa, which may be relevant to the increased mucosal damage associated with cagA positive H pylori infection.
Antigens, Bacterial↗
Relevance of antibiotic sensitivities in predicting failure of omeprazole, clarithromycin, and tinidazole to eradicate Helicobacter pylori.
Omeprazole 20mg once (od) or twice daily (bd), clarithromycin 250mg bd, and tinidazole 500 mg bd for 7 days (OCT) is an effective regimen against Helicobacter pylori, but the effect of 5-nitroimidazole resistance is unclear. We aimed to evaluate this using the disc diffusion technique and E-test to assess 5-nitroimidazole resistance. H. pylori was cultured from antral biopsies of infected patients as determined by 13C-urea breath test (13C-UBT), histology, and/or rapid urease test. Patients were prescribed OCT, and H. pylori eradication was assessed by 13C-UBT at least 4 weeks after completion of therapy. Antibiotic sensitivities to metronidazole and clarithromycin were evaluated by the disc diffusion method and by minimum inhibitory concentration (MIC) using the E-test. One hundred and forty-one H. pylori-infected patients were enrolled into the study and the organism was successfully cultured in 119 patients (84%). The overall eradication rate was 125/141 (89%). OCT was successful in 62/69 (90%) patients harboring fully sensitive strains of H. pylori compared with 42/45 (93%) of patients with strains that were resistant to metronidazole alone (P = 0.74, Fisher's exact test). MIC was assessed in 22 samples. Using a cut-off point of > 32 microg/ml to define metronidazole resistance, eradication rates were higher against sensitive (9/12; 75%) compared with resistant (3/10; 30%) strains (P = 0.08, Fisher's exact test). 5-Nitroimidazole resistance assessed by the disc diffusion technique is not helpful in predicting OCT failure, but the E-test may be of value.
Adult↗
Randomised double blind controlled study of recurrence of gastric ulcer after treatment for eradication of Helicobacter pylori infection.
OBJECTIVE: To determine whether eradication of Helicobacter pylori infection reduces recurrence of benign gastric ulceration. DESIGN: Randomised, double blind, controlled study. Patients were randomised in a 1:2 ratio to either omeprazole 40 mg once daily for eight weeks or the same treatment plus amoxycillin 750 mg twice daily for weeks 7 and 8. A 12 month untreated follow up ensued. SETTING: Teaching and district general hospitals between 1991 and 1994. SUBJECTS: 107 patients with benign gastric ulcer associated with H pylori. MAIN OUTCOME MEASURES: Endoscopically confirmed relapse with gastric ulcer (analysed with life table methods), H pylori eradication, and healing of gastric ulcers (Mantel-Haenszel test). RESULTS: 172 patients were enrolled. Malignancy was diagnosed in 19; 24 were not infected with H pylori; four withdrew because of adverse events; and 18 failed to attend for start of treatment, leaving 107 patients eligible for analysis (35 omeprazole alone; 72 omeprazole plus amoxycillin). In the omeprazole/amoxycillin group 93% (67/72; 95% confidence interval 84% to 98%) of gastric ulcers healed and 83% (29/35; 66% to 94%) in the omeprazole group (P = 0.103). Eradication of H pylori was 58% (42/72; 46% to 70%) and 6% (2/35; 1% to 19%) (P < 0.001) and relapse after treatment was 22% (16/72) and 49% (17/35) (life table analysis, P < 0.001), in the two groups, respectively. The recurrence rates were 7% (3/44) after successful H pylori eradication and 48% (30/63) in those who continued to be infected (P < 0.001). CONCLUSIONS: Eradication of H pylori reduces relapse with gastric ulcer over one year. Eradication rates achieved with this regimen, however, are too low for it to be recommended for routine use.
Amoxicillin↗
Validation of a rapid whole blood test for diagnosing Helicobacter pylori infection.
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Adult↗
Patient factors that predict failure of omeprazole, clarithromycin, and tinidazole to eradicate Helicobacter pylori.
Omeprazole (20 mg od/b.d.), clarithromycin (250 mg b.d.) and tinidazole (500 mg b.d. for 7 days) [OCT] is an effective regimen against Helicobacter pylori. However, treatment fails in 5%-10% of patients and the reasons for this are not clear. We investigated patient factors that independently predicted failure of this regimen. H. pylori-positive patients were prescribed OCT and the success of treatment was evaluated by the 13C-urea breath test at least 4 weeks after completion of therapy. Patients were prospectively interviewed on past medical history of peptic ulcer and H2-receptor antagonist (H2RA) pre-treatment, smoking history, and alcohol intake. Data were also collected on age, gender, and endoscopic diagnosis to determine factors predicting failure of OCT. H. pylori eradication was achieved in 238 of 273 patients [87%-95% confidence intervals (CI), 83%-91%]. Age, alcohol intake, past medical history of peptic ulcer and peptic ulcer at endoscopy were not independently associated with treatment failure. H. pylori eradication with OCT was less successful in women (P = 0.02), in patients who had received H2RA pre-treatment (P = 0.02), and in smokers (P = 0.02) when evaluated by multiple logistic regression. These findings indicate that OCT is less effective in smokers and in patients who receive H2RA pre-treatment suggesting that these agents should be avoided, if possible, before the patient commences therapy. H. pylori eradication was less successful in women; this result needs further evaluation.
Adult↗
Helicobacter pylori infection is related to atheroma in patients undergoing coronary angiography.
OBJECTIVES: Helicobacter pylori infection has been related to an increased risk of ischaemic heart disease (IHD) possibly by raising plasma fibrinogen. The evidence for this association is conflicting. Furthermore, no attempt has been made to distinguish between an effect on atheroma and thrombosis. We have determined the association of H. pylori status with IHD assessed by coronary angiography. We have also evaluated the influence of H. pylori infection on haemostatic factors. METHODS: Caucasian patients undergoing coronary angiography for suspected IHD were recruited. H. pylori status was determined by serology (Helico G). Plasma fibrinogen was measured by the Clauss assay. Coronary angiograms were assessed and significant atheroma defined as > or = 50% stenosis. A history of myocardial infarction was ascertained by WHO criteria. RESULTS: 292 patients were recruited (median age 59, 95 female); 204 (70%) patients had IHD and 185 (64%) of all patients were H. pylori-positive; 68% patients with IHD were H. pylori-positive compared with 50% without IHD (P = 0.003). When adjusted for other risk factors by logistic regression, H. pylori remained significantly associated with IHD (odds ratio = 2.4, 95% CI = 1.2-5.1, P = 0.02). H. pylori status was not related to a history of myocardial infarction. Circulating levels of PAI-1, vWF, Factor VII and fibrinogen were not related to H. pylori status. CONCLUSION: This study suggests that infection with H. pylori is associated with coronary atheroma, but that this relationship is unlikely to be mediated through raised plasma fibrinogen.
Adult↗
Chronic dyspepsia: who needs endoscopy?
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Barrett Esophagus↗