Biomedical subjects
Publications and source records attributed to A T Axon.
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BACKGROUND: Both patients and government demand proof of quality of care and value for money. Our unit ist in a large teaching hospital, performing over 6000 procedures per year. We have designed and implemented a Quality Assurance (QA) program, the basis of which we believe could be a model for endoscopy QA. METHODS: A QA team was formed and a literature search undertaken. An initial 3 month audit was then performed into indications for, and complications of, all procedures. The results of this initial audit led us to concentrate on colonoscopy and ERCP. The specific items of data collected were based on the "Core Quality Indicators" developed by the American Society for Gastrointestinal Endoscopy (ASGE). We also analysed data relating to endoscope disinfection, equipment failure and carried out a patient satisfaction survey. The data were presented at 3-monthly QA meeting, and appropriate action taken. RESULT: We performed a detailed audit of ERCP (217 procedures) and colonoscopy (904 procedures). Patients risk was stratified using the American Society of Anaesthesiology (ASA) classification. Using these data we established our technical success and complication rates for colonoscopy and ERCP. Audit of equipment revealed that on average an endoscope was away for repair 9 % of the time. Contamination of endoscopes was frequent with glutaraldehyde disinfection; the rate of contamination fell dramatically when we changed our disinfection method. CONCLUSION: A QA program can be implemented in busy endoscopy units. There are significant problems, however, in ensuring that such a program is effective: these include inadequate funding/staffing, lack of suitable information technology and lack of clear guidelines for dealing with poor performance.
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Interleukin-18 (IL-18), a cytokine that promotes Th1 responses, is processed to the active mature protein by caspase-1. The effects of Helicobacter pylori infection on gastric IL-18 and caspase-1 were examined. In antral mucosa, IL-18 mRNA expression was greater (P<.01) in H. pylori-positive (n=40) than in H. pylori-negative patients (n=29) with normal mucosa. Inactive precursor (24 kDa) and mature (18 kDa) IL-18 were present in antral biopsy specimens from uninfected and infected subjects. In corpus mucosa, mature IL-18 and a 16-kDa protein, corresponding to inactive IL-18, were present. Active caspase-1 p20 subunit was detected in antral and corpus mucosa of infected and uninfected subjects. These data show that, although H. pylori infection is associated with increased antral IL-18 mRNA expression, mature IL-18 protein and active caspase-1 p20 are present in mucosa of both H. pylori-infected and -uninfected subjects. IL-18 may have an important role in promoting gastric Th1 responses in H. pylori infection.
BACKGROUND: Population Helicobacter pylori screening and treatment has been advocated as a means of reducing mortality from gastric cancer. The optimum Helicobacter pylori eradication therapy to use in this setting is uncertain. AIMS: To compare efficacy of seven days of omeprazole, clarithromycin and either metronidazole, or amoxycillin in Helicobacter pylori positive subjects detected by population screening. PATIENTS: Helicobacter pylori positive patients from the placebo group of a population screening and treatment trial were invited to take part in the investigation. METHODS: Patients were randomised to receive either omeprazole, clarithromycin and metronidazole or omeprazole, clarithromycin and amoxycillin, and Helicobacter pylori eradication was verified with a 13C-urea breath test at least four weeks after completion of therapy. RESULTS: A total of 221 patients took part in the study and 210 completed the protocol. Treatment was successful in 93/111 [84%) patients allocated to omeprazole, clarithromycin and metronidazole and in 96/110 (87%) allocated to omeprazole, clarithromycin and amoxycillin in an intention-to-treat analysis (p=0.46). Per protocol eradication rates were 93/107 (87%) in the metronidazole, and 96/103 (93%) amoxycillin group (p=0.129). CONCLUSIONS: There was no significant difference between the two regimens. The eradication rates achieved are comparable with previous studies in both dyspepsia and peptic ulcer patients.
BACKGROUND & AIMS: Observational studies have suggested that Helicobacter pylori may protect against gastrointestinal reflux disease (GERD), but these results could be due to bias or confounding factors. We addressed this in a prospective, double blind, randomized, controlled trial. METHODS: H. pylori-positive patients with at least a 1-year history of heartburn with a normal endoscopy or grade A esophagitis were recruited. Patients were randomized to 20 mg omeprazole, 250 mg clarithromycin, and 500 mg tinidazole twice a day for 1 week or 20 mg omeprazole twice a day and identical placebos. A second concurrently recruited control group of H. pylori-negative patients were given open label 20 mg omeprazole twice a day for 1 week. All patients received 20 mg omeprazole twice a day for the following 3 weeks and 20 mg omeprazole once daily for a further 4 weeks. Omeprazole was discontinued at 8 weeks and patients were followed up for a further 10 months. A relapse was defined as moderate or severe reflux symptoms. H. pylori eradication was determined by 13C-urea breath test. RESULTS: The H. pylori-positive cases were randomized to antibiotics (n = 93) or placebo (n = 97). Relapse of GERD occurred in 83% of each of the antibiotic, placebo, and H. pylori-negative groups during the 12-month study period. Life tables revealed no statistical difference between the 2 H. pylori-positive groups (log rank test, P = 0.84) or between the 3 groups (log rank test, P = 0.94) in the time to first relapse. Two patients in each group developed grade B esophagitis at 12 months. CONCLUSIONS: H. pylori eradication therapy does not seem to influence relapse rates in GERD patients.
We are now finding more malignancies in their early stages than previously. Attempts to ablate these lesions are difficult and do not provide the histological information required to decide on further treatment. Surgery is difficult to justify, as only a minority of lesions are associated with lymph node metastases and lesions may not become clinically relevant within the lifetime of an elderly patient. Endoscopic mucosal resection allows cancers to be resected at minimal cost, morbidity and mortality. It is also the most reliable investigation when assessing lesions which are suspicious for containing early cancer. After endoscopic removal, histological assessment of depth of penetration and a search for invasion into lymphatics or venules allows the risk of microscopic lymph node metastases to be predicted. The risk of developing metastatic disease can then be balanced against the risks of surgery in view of the patient's age and health.
Variant Creutzfeldt-Jakob disease (vCJD) is a transmissible form of spongiform encephalopathy believed to be contracted from the consumption of bovine spongiform encephalopathy (BSE) infected beef products. To date over 100 individuals have developed this incurable disease. There have been no documented cases of iatrogenic infection, but there is a theoretical risk that surgical procedures could transmit the disease. This review describes the background of the disease and assesses the possible risks of transmission through endoscopic procedures. The risk of transmission by endoscopy is small and probably negligible if suitable procedures are followed. The greatest potential danger arises from healthy individuals who are incubating the disease. Pathological prions (PrP(sc)) may be found in lymphatic tissue of these individuals (particularly tonsils), but smaller amounts have been identified in the appendix and Peyer's patches. These prions are resistant to all forms of conventional sterilization. There is a theoretical risk that biopsy forceps and the operating channel of endoscopes could become contaminated. This review gives recommendations as to how these small risks can be minimized. They include the employment of single-use forceps for biopsies taken from the terminal ileum, greater attention to the maintenance of endoscopic equipment and accessories, more rigorous manual cleaning of endoscopic equipment and the use of well designed, disposable cleaning brushes for the operating channel of the endoscope.
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BACKGROUND: There is increasing evidence that reflux of bile plays a part in the pathogenesis of Barrett's oesophagus. Bile injury to the gastric mucosa results in a "chemical" gastritis in which oedema and intestinal metaplasia are prominent. AIM: To determine if patients with Barrett's oesophagus have more bile related changes in antral mucosa than patients with uncomplicated gastro-oesophageal reflux disease (GORD) or non-ulcer dyspepsia (NUD). PATIENTS AND METHODS: Patients were identified by a retrospective search of pathology records and those with a clinically confirmed diagnosis of either Barrett's oesophagus or reflux oesophagitis who had oesophageal and gastric biopsies taken at the same endoscopy and had no evidence of Helicobacter pylori infection entered the study. Control biopsies were taken from H pylori negative NUD patients. Antral biopsies were examined "blind" to clinical group and graded for a series of histological features from which the "reflux gastritis score" (RGS) and "bile reflux index" (BRI) could be calculated. The reproducibility of these histological scores was tested by a second pathologist. RESULTS: There were 100 patients with Barrett's, 61 with GORD, and 50 with NUD. The RGSs did not differ between groups. BRI values in the Barrett's group were significantly higher than those in GORD subjects (p=0.014) which in turn were higher than those in NUD patients (p=0.037). Similarly, the frequency of high BRI values (>14) was significantly greater in the Barrett's group (29/100; 29%) than in the GORD (9/61; 14.8%) or NUD (4/50; 8%) group. However, agreement on BRI values was "poor", indicating limited applicability of this approach. CONCLUSION: Patients with Barrett's oesophagus have more evidence of bile related gastritis than subjects with uncomplicated GORD or NUD. The presence of bile in the refluxate could be a factor in both the development of "specialised" intestinal metaplasia and malignancy in the oesophagus.
AIM: Chemokines that play a primary role in active inflammation are increased in gastric mucosa infected with Helicobacter pylori. Cigarette smoking increases the risk of peptic ulcer disease and gastric cancer, whereas alcohol might exert an antibacterial role. The aim of this study was to examine the association between smoking or alcohol consumption and mucosal chemokine mRNA expression in H pylori associated gastritis. METHODS: Gastric biopsy specimens were obtained from 46 patients with dyspepsia who were infected with H pylori, and total RNA was extracted. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed to quantify the mRNA expression of three C-X-C chemokines (interleukin 8 (IL-8), growth related oncogene alpha (GRO alpha), epithelial neutrophil activating protein 78 (ENA-78)) and two C-C chemokines (regulated on activation normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein 1 (MCP-1)). RESULTS: GRO alpha and ENA-78 mRNA expression was significantly increased (p < 0.05) in 22 smokers compared with 24 non-smokers; however, no difference was seen in the expression of IL-8, RANTES, and MCP-1 mRNA. No differences were observed in chemokine mRNA expression in relation to alcohol consumption. CONCLUSIONS: The increased C-X-C chemokine mRNA expression seen in smokers might play a role in inducing enhanced inflammatory activity in gastritis and the consequent severe diseases associated with H pylori infection.
Helicobacter pylori infection is associated with elevated gastric mucosal concentrations of the lipid peroxidation product malondialdehyde and reduced gastric juice vitamin C concentrations. Malondialdehyde can react with DNA bases to form the mutagenic adduct malondialdehyde-deoxyguanosine (M(1)-dG). We aimed to determine gastric mucosal levels of M(1)-dG in relation to H. pylori infection and malondialdehyde and vitamin C concentrations. Patients (n = 124) attending for endoscopy were studied. Levels of antral mucosal M(1)-dG were determined using a sensitive immunoslot-blot technique; antral mucosal malondialdehyde was determined by thiobarbituric acid extraction, and gastric juice and antral mucosal ascorbic acid and total vitamin C were determined by high-performance liquid chromatography. Sixty-four H. pylori-positive patients received eradication therapy, and endoscopy was repeated at 6 and 12 months. Levels of M(1)-dG did not differ between subjects with H. pylori gastritis (n = 85) and those with normal mucosa without H. pylori infection (n = 39; 56.6 versus 60.1 adducts/10(8) bases) and were unaffected by age or smoking habits. Malondialdehyde levels were higher (123.7 versus 82.5 pmol/g; P < 0.001), gastric juice ascorbic acid was lower (5.7 versus 15.0 micromol/ml; P < 0.001), and antral mucosal ascorbic acid was unchanged (48.0 versus 42.7 micromol/g) in H. pylori gastritis compared with normal mucosa. Multiple regression analysis revealed that M(1)-dG increased significantly with increasing levels of malondialdehyde, antral ascorbic acid, and total antral vitamin C. M(1)-dG levels were unchanged 6 months (63.3 versus 87.0 adducts/10(8) bases; P = 0.24; n = 38) and 12 months (66.7 versus 77.5 adducts/10(8) bases; P = 0.8; n = 13) after successful eradication of H. pylori. M(1)-dG thus is detectable in gastric mucosa, but is not affected directly by H. pylori.
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A number of risk factors have been linked epidemiologically with gastric cancer, but studies of DNA damage in gastric epithelial cells are limited. The comet assay is a simple technique for determining levels of DNA damage in individual cells. In this study, we have validated the comet assay for use in epithelial cells derived directly from human gastric biopsies, determined optimal conditions for biopsy digestion and investigated the effects of oxidative stress and digestion time on DNA damage. Biopsies taken at endoscopy were digested using combinations of pronase and collagenase, ethylenediaminetetra-acetic acid (EDTA) and vigorous shaking. The resultant cell suspension was assessed for cell concentration and epithelial cell and leukocyte content. A score for DNA damage, the comet %, was derived from the cell suspension, and the effect of various digestion conditions was studied. Cells were incubated with H(2)O(2) and DNA damage was assessed. Pronase and collagenase provided optimum digestion conditions, releasing 1. 12x10(5) cells per biopsy, predominantly epithelial. Of the 23 suspensions examined, all but three had leukocyte concentrations of less than 20%. The comet assay had high inter-observer (6.1%) and inter-assay (4.5%) reproducibility. Overnight storage of the biopsy at 4 degrees C had no significant effect on DNA migration. Comet % increased from a median of 46% in untreated cells to 88% in cells incubated for 45 min in H(2)O(2) (p=0.005). Serial 25-min digestions were performed on biopsies from 13 patients to release cells from successively deeper levels in the crypt. Levels of DNA migration were significantly lower with each digestion (r=-0.94, p<0.001), suggesting that DNA damage is lower in younger cells released from low in the gastric crypt. The comet assay is a reproducible measure of DNA damage in gastric epithelial cells. Damage accumulates in older, more superficial cells, and can be induced by oxidative stress.
BACKGROUND: Infection with Helicobacter pylori is the main cause of peptic-ulcer disease. Treatment of this infection might lower the prevalence of dyspepsia in the community and improve quality of life. We investigated this possibility in a double-blind randomised controlled trial. METHODS: Individuals aged 40-49 years were randomly selected from the lists of 36 primary-care centres. A researcher interviewed participants with a validated dyspepsia questionnaire and the psychological general wellbeing index (PGWB). H. pylori status was assessed by the carbon-13-labelled urea breath test. Infected participants were randomly assigned active treatment (omeprazole 20 mg, clarithromycin 250 mg, and tinidazole 500 mg, each twice daily for 7 days) or identical placebo. Participants were followed up at 6 months and 2 years. FINDINGS: Of 32,929 individuals invited, 8455 attended and were eligible; 2324 were positive for H. pylori and were assigned active treatment (1161) or placebo (1163). 1773 (76%) returned at 2 years. Dyspepsia or symptoms of gastro-oesophageal reflux were reported in 247 (28%) of 880 in the treatment group and 291 (33%) of 871 in the placebo group (absolute-risk reduction 5% [95% CI 1-10]). H. pylori treatment had no significant effect on quality of life (mean difference in PGWB score between groups 0.86 [-0.33 to 2.05]). INTERPRETATION: Community screening and treatment for H. pylori produced only a 5% reduction in dyspepsia. This small benefit had no impact on quality of life.
BACKGROUND: Flat and depressed colorectal tumours were originally thought to be unique to the Japanese population. Recently there have been reports of flat and depressed lesions in western countries but they have been thought to be uncommon. METHODS: In this prospective study, 1000 consecutive patients attending for routine colonoscopy were examined for flat or depressed lesions. The examinations were done by one European colonoscopist using methods developed in Japan. FINDINGS: 321 adenomas were found: 202 (63%) were polypoid, 36% (117) were flat and 2 (0.6%) appeared depressed. Most adenomas contained areas of mild or moderate dysplasia but 10% (31) were severely dysplastic. Six Dukes' A adenocarcinomas were identified together with 25 more advanced adenocarcinomas. The likelihood of Dukes' A cancer or severe dysplasia increased from 4% (3/70) in small flat lesions, to 6% (9/154) in small polyps, 16% (8/50) in larger polyps, 29% (14/49) in large flat lesions, and 75% (3/4) in depressed lesions. 54% (20/37) lesions containing severe dysplasia or Dukes' A carcinoma were flat or depressed. INTERPRETATION: The polyp-carcinoma hypothesis prompts colonoscopists to search only for polypoid lesions when screening for cancer, and many early colorectal neoplasms may therefore be missed. Colonoscopists require training in the recognition of flat and depressed lesions to detect colorectal tumours in the early stages.
Helicobacter pylori is recognized to be a serious pathogen, but there is still controversy as to who should be treated. There is consensus for treatment of Helicobacter-positive peptic ulcer and B-cell lymphoma. Lymphocytic gastritis and giant-fold gastritis (Ménétrièr's disease) may also respond to treatment. Patients with func-tional dyspepsia have a 20% placebo response with a 5-10% 'eradication' response, results not dissimilar from empirical treatment with a proton pump inhibitor. A 'test and treat' policy for patients with uninvesti-gated dyspepsia remains controversial. Some have suggested that eradication may increase the risk of GERD, or predispose to adenocarcinoma at the gastro-oesophageal junction. However, PPI treatment without Helicobacter eradication induces greater inflammation in the gastric corpus, the phenotype associated with non-cardia gastric cancer. A minority believe that Helicobacter should be eradicated in all individuals. When choosing treatment it is logical to start with a combination of antibiotics that, in the event of failure, will allow a second combination to be used without overlap.