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Biomedical subjects

M F Dixon

Publications and source records attributed to M F Dixon.

At least 37 records · Page 2Linked to original sources
PubMed2001

Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease.

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.

Adult↗
PubMed2001

Bile reflux gastritis and Barrett's oesophagus: further evidence of a role for duodenogastro-oesophageal reflux?

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.

Adult↗
PubMed2001

Influence of smoking and alcohol on gastric chemokine mRNA expression in patients with Helicobacter pylori infection.

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.

Alcohol Drinking↗
PubMed2000

Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK.

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.

Adenocarcinoma↗
PubMed2000

A comparison of microsatellite instability in early onset gastric carcinomas from relatively low and high incidence European populations.

We have investigated the genetic basis of gastric carcinomas occurring in patients aged under 40 years from a Portuguese population with a relatively high incidence of gastric cancer. We analysed a panel of 12 microsatellite loci in DNA extracted from gastric carcinomas arising in 16 patients aged 24-39 years from Braga, Portugal. Overall, microsatellite instability (MI) in at least 1 locus was detected in 44% (7 of 16) of carcinomas. A single patient demonstrated a mutator phenotype suggestive of the hereditary nonpolyposis colorectal cancer syndrome with instability in 82% of loci. This carcinoma showed loss of expression of the hMLH1 mismatch repair protein. In a previous study, we found no evidence of MI among 10 cases of early onset gastric carcinomas from an English population, which has a relatively low incidence of gastric cancer. Comparing the 2 series, we found that there was a significant difference (p = 0.04) in the prevalence of MI (at least 1 marker affected). This geographical difference in low-level MI may be related to a significantly higher prevalence of background chronic atrophic gastritis (8 of 16 vs. 0 of 8) and Helicobacter pylori infection (15 of 16 vs. 2 of 8) in Portuguese carcinomas compared with English cases. Genetic mechanisms underlying the hereditary non-polyposis colorectal cancer syndrome may play a role in a small number of early onset gastric carcinomas. The difference in prevalence of low-level MI between these relatively high and low incidence European populations requires further investigation.

Adult↗
PubMed2000

Changing patterns of Helicobacter pylori gastritis in long-standing acid suppression.

BACKGROUND: Helicobacter pylori colonization and associated inflammation are influenced by local acid output. Infected subjects with acid-related diseases, such as gastroesophageal reflux disease (GERD) are likely to have an antral-predominant gastritis. We hypothesized that long-term acid suppression would result in relatively greater bacterial colonization in the corpus leading to diffuse or corpus-predominant gastritis and that this would be prevented by prior H. pylori eradication. MATERIALS AND METHODS: To investigate this, we conducted a prospective, double-blind trial of the effect on gastric histology of 12-month maintenance treatment with omeprazole in H. pylori-positive GERD patients randomly assigned to either an eradication or omeprazole-alone regime. A control group of 20 H. pylori-negative GERD patients also received omeprazole throughout the study period. Biopsies taken at baseline and at 12 months were graded "blind" by a single observer according to the updated Sydney System. The 41 H. pylori-positive subjects with grade B or C esophagitis were randomly assigned (20 to omeprazole alone, 21 to eradication) and 33 subjects completed the 12-month study. RESULTS: There was a significant decline in antral chronic inflammation in initially positive patients between baseline and end in both the eradication group (p =.035) and the omeprazole-alone group (p =.008). However, corpus chronic inflammation increased in the omeprazole-alone group (p =.0156) but decreased in the eradication group. The change toward corpus predominance between baseline and end for the omeprazole-alone group is highly significant (p =.0078). Furthermore, 5 of 11 in the omeprazole-alone group developed mild corpus atrophy, compared to 0 of 8 who had undergone H. pylori eradication. The change in frequency of corpus atrophy between the two groups is significant (p =.02). CONCLUSION: In H. pylori-positive subjects with GERD, long-term acid suppression leads to a shift from antral- to corpus-predominant gastritis that can be prevented by prior eradication. The shift is accompanied by an increase in corpus atrophy. H. pylori infection should be eradicated prior to long-term acid suppression with proton pump inhibitors.

Adolescent↗
PubMed2000

Patterns of inflammation linked to ulcer disease.

Peptic ulcers are accompanied by different patterns of chronic gastritis and duodenitis that generally run parallel to the topography of colonization by Helicobacter pylori (H. pylori). Duodenal ulcers arise on a background of a gastroduodenitis; the gastritis is antrum-predominant while the duodenitis requires acid-induced gastric metaplasia in the duodenal mucosa before bacterial colonization can occur. The colonized and inflamed metaplastic areas in the duodenum (and inflamed pre-pyloric antrum) are the initial sites of ulceration. Proximal gastric ulcers arise in a diffuse (pan-) gastritis or a corpus-predominant H. pylori gastritis when the weakened gastric mucosa (especially in the antrum-body transitional zone) is susceptible to ulceration even in the presence of subnormal acid production. These distinctive patterns of gastritis are sufficiently consistent for them to be used to predict ulcer risk.

Duodenal Ulcer↗
PubMed2000

Gastroduodenal ulcers in the Helicobacter pylori era.

The aim of the study was to evaluate the current spectrum of gastroduodenal ulcers in children referred to a regional paediatric unit in the United Kingdom. During a 5-y period (1994-98), all children with a visibly discrete gastric and/or duodenal ulcer diagnosed at endoscopy were prospectively identified. Patients with ulcers associated with Helicobacter pylori gastritis underwent repeat endoscopy 2-3 mo after medical treatment. Thirty-seven children, 21 boys and 16 girls of median age 11 y (range 7 mo to 16 y), had gastric and/or duodenal ulceration. Specific aetiological factors were identified in 21 of 22 with H. pylori negative ulcers, including Crohn's disease (n = 6), coeliac disease (n = 4) and treatment with ulcerogenic drugs (n = 4). Fifteen children (41%) had ulcers associated with H. pylori gastritis, including all 10 children with a chronic ulcer. Endoscopically confirmed ulcer healing was achieved in 14 of these using a 1 wk triple therapy regimen (omeprazole and a combination of two antibiotics). In conclusion, the recognized spectrum and the management of gastroduodenal ulceration have changed during the last decade. Although H. pylori gastritis is an important aetiological factor, a wide range of other conditions needs to be considered. Surgical intervention is only rarely necessary.

Acute Disease↗
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

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

Histological identification of Helicobacter pylori: comparison of staining methods.

AIM: To determine whether two recently described staining methods (the modified McMullen's and the Helicobacter pylori silver stain HpSS methods) used for the histological identification of H pylori organisms are superior to two established techniques (the modified Giemsa and anti-H pylori antibody immunostain) in terms of availability, reproducibility, rapidity, sensitivity, and cost. METHODS: Histological sections from 63 paired gastric biopsies from adult patients previously investigated for dyspepsia were stained with the four methods and these were assessed blindly and independently by two observers. Of the 63 patients, 30 were originally negative in all tests for H pylori infection, 30 were positive, and the remaining three cases had discordant results using a combination of five tests (rapid biopsy urease test, urea breath test, culture, serology, and histology). RESULTS: Interobserver agreement was best with the antibody method (98%), followed by the McMullen's (90%), Giemsa (87%), and HpSS (85%). Of the 60 "gold standard" positive and negative cases, 30 were positive by the modified Giemsa stain, 29 by the McMullen's method, 29 by HpSS, and 30 by the antibody stain. However, there were two false positives with the HpSS method. The modified Giemsa is the cheapest and easiest to perform technically. CONCLUSIONS: When H pylori are present, careful examination will almost always reveal them, whichever of these stains is used. However, the modified Giemsa stain is the method of choice because it is sensitive, cheap, easy to perform, and reproducible.

Adult↗
PubMed2000

Small bowel haemangioma with local lymph node involvement presenting as intussusception.

Gastrointestinal haemangiomas make up 0.05% of all intestinal neoplasms. They are sometimes multiple and usually present with pain, bleeding, and obstruction. An associated haemangiomatous change in regional lymph nodes has not been reported previously. A woman of 21 years presented with abdominal pain and vomiting. Abdominal ultrasound and computed tomography scan showed a lower abdominal mass. Laparotomy revealed a small bowel tumour causing an intussusception together with enlarged mesenteric lymph nodes. Pathological examination revealed a small bowel haemangioma with mesenteric node involvement. The pathogenesis of haemangiomatous involvement of lymph nodes is discussed. Hamartomatous change is the likely cause in this patient.

Adult↗
PubMed2000

International comparability of the pathological diagnosis for early cancer of the digestive tract: Munich meeting.

Large differences have been found between Western and Japanese pathologists' diagnosis of adenoma/dysplasia versus early carcinoma for gastric, esophageal. and colorectal epithelial neoplastic lesions. In this study we examined whether differences in experience in gastrointestinal pathology can to some extent explain these differences in diagnostic practice. Three Japanese, one British, and two German pathologists with much experience and one North American pathologist with less experience in routine diagnostic work reviewed 52 microscopic slides: 16 gastric, 24 esophageal, and 12 colorectal biopsy and resection specimens obtained from patients with lesions ranging from early carcinoma to adenoma, dysplasia, and regenerative epithelium. The extent of agreement between the diagnoses of the four individual Western pathologists and the most common Japanese diagnoses was assessed by kappa statistics. For the 16 gastric lesions, a diagnosis of suspected or definite carcinoma was made by the Japanese pathologists in 69%-75% of the slides, by three experienced Western pathologists in 56%-63% (high kappa values: 0.61, 0.64, 0.65), and by the less experienced Western pathologist in only 31% of the slides (low kappa value: 0.10). For the 24 specimens of esophageal squamous lesions, carcinoma in situ and suspected or definite carcinoma were diagnosed by the Japanese in 96%-100% and by the Western pathologists in 63%-88% of the slides (low kappa values: 0.17, 0.25, 0.25, 0.27). For the 12 colorectal lesions, the Japanese diagnosed suspected or definite carcinoma in 58%-83%, whereas all Western pathologists followed the World Health Organization definition of colorectal carcinoma and diagnosed suspected or definite carcinoma in only 0-42% of the slides (kappa values: 0.04, 0.10,0.12, 0.49). In conclusion, there were few differences in diagnoses between experienced Western and Japanese pathologists for gastric lesions but considerable differences for esophageal and colorectal lesions. The differences in the diagnosis of adenoma/dysplasia versus early carcinoma between Western and Japanese pathologists found in previous studies may in large part be attributable to differences in experience with regard to gastric neoplasia and to differences in interpretation and nomenclature with regard to esophageal and colorectal neoplasia.

Biopsy↗
PubMed1999

The gastric transitional zones: neglected links between gastroduodenal pathology and helicobacter ecology.

The gastric transitional zones are the junctional zones between the different types of mucosa: antral-body, body-cardia, and antrum-duodenum. In this article, the importance of the transitional zone in determining disease outcome, specifically duodenal ulcer, gastric ulcer, and possibly gastric cancer, is reviewed. Both gastric ulcers and duodenal ulcers are located immediately adjacent to the transitional zones. The transitional zones are dynamic rather than static areas. Local acid levels determine the behavior of Helicobacter pylori at the antral-body transitional zone and, as a consequence, the geographic distribution of gastritis in the stomach and the formation of duodenal ulcer and gastric ulcer. This review also explains that diffuse antral gastritis and multifocal atrophic gastritis are part of the same disease and not separate entities.

Atrophy↗
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↗