A single centre's 20 years' experience of columnar-lined (Barrett's) oesophagus diagnosis.

BACKGROUND: The pattern of oesophageal carcinoma type has been changing for some time in a number of countries, with adenocarcinoma becoming more frequent OBJECTIVE: To investigate the prevalence of columnar-lined (Barrett's) oesophagus and oesophageal adenocarcinoma in Barrett's oesophagus during a 20-year period in a single centre. METHODS: All upper gastrointestinal endoscopy and histology reports for the period January 1977 to December 1996 inclusive were reviewed. Data were analysed from patients who had histologically proven Barrett's oesophagus. The data were analysed as a single cohort and in five-year bands according to the date of diagnosis. RESULTS: Of 44,721 endoscopies, 636 Barrett's oesophagus cases were diagnosed; 508 (323 males 185 females; M:F ratio 1.7) were histologically proven. The frequency of Barrett's oesophagus detection increased steadily from 0.2% to 1.6% of all endoscopies per five-year band. The M:F ratio and the mean ages at diagnosis (61 years, range 60-63 for males and 69 years, range 68-79 for females) remained constant throughout. Barrett's oesophagus was diagnosed at a younger age in males (peak 60-69 years) compared to females (peak 70-79 years). The male oesophageal adenocarcinoma incidence (11.1%) was almost twice that in females (6.5%). In the majority (81%), the initial diagnosis of oesophageal adenocarcinoma and Barrett's oesophagus was made concurrently. CONCLUSIONS: The increasing Barrett's oesophagus frequency may reflect an increasing incidence or recognition of this condition or both. Barrett's oesophagus males are more likely to develop oesophageal adenocarcinoma than females.

Treatment of Helicobacter pylori infection.

Helicobacter pylori infection is now recognised as the major cause of chronic active gastritis and peptic ulcer disease and eradication of the infection will prevent recurrence of the majority of such ulcers. A large number of different treatment combinations have been tried, but 100% H pylori eradication has not been achieved due to the use of wrong drug combinations or dosages, non-compliance and development of primary or acquired bacterial resistant strains. However, consistent 95-96% H pylori eradication can now be achieved with triple therapy employing a high-dose proton pump inhibitor twice daily together with any two of the following drugs: nitroimidazole, clarithromycin, or amoxycillin in appropriate dosages taken two to three times daily and all concurrently for one week. The problem of resistant bacterial strains has to be addressed, as this development is one of the consequences of failed eradication treatment.

Overestimation of myocardial infarct size on two-dimensional echocardiograms due to remodelling of the infarct zone.

OBJECTIVE: To assess the effect of early regional diastolic shape distortion or bulging of infarct zones due to infarct expansion on estimates of regional left ventricular dysfunction and infarct size by two-dimensional echocardiographic imaging. DESIGN: Quantitative two-dimensional echocardiograms from patients with a first Q wave myocardial infarction and creatine kinase infarct size data, and normal subjects, were subjected to detailed analysis of regional left ventricular dysfunction and shape distortion in short-axis images by established methods. Regional left ventricular asynergy (akinesis and dyskinesis) and shape distortion indices (eg, peak [Pk]/radius [ri]) were measured on endocardial diastolic outlines of short-axis images in 43 postinfarction patients (28 anterior and 15 inferior, 5.9 h after onset) and 11 normal subjects (controls). In the infarction group, endocardial surface area of asynergy was calculated by three-dimensional reconstruction of the images and infarct size from serial creatine kinase blood levels. MAIN RESULTS: Diastolic bulging of asynergic zones was found in all infarction patients. The regional shape distortion indices characterizing the area between the 'actual' bulging asynergic segment and the derived 'ideal' circular segment (excluding the bulge) on indexed sections were greater in infarct than control groups (Pk/ri 0.31 versus 0, P < 0.001) and greater in anterior than inferior infarction subgroups (Pk/ri 0.39 versus 0.16, P > 0.001). Importantly, the degree of distortion correlated with overestimation of asynergy (r = 0.89, P < 0.001), and the relation between infarct size and total 'ideal' asynergy showed a leftward shift from that with 'actual' asynergy. CONCLUSIONS: Early regional diastolic bulging of the infarct zone results in overestimation of regional ventricular dysfunction, especially in patients with anterior infarction. This effect should be considered when assessing effects of therapy on infarct size, remodelling and dysfunction using tomographical imaging.

Early gastric cancer: follow-up after gastrectomy in 159 patients.

The postoperative course of 159 patients with early gastric cancer operated on between 1974 and 1987 was followed for a median of 7.3 years. The cumulative 10-year survival rate(s.e.) calculated using follow-up data to the end of 1989 was 90.6(2.7) per cent excluding operative death and that from causes other than gastric cancer, or 86.3(3.0) per cent when operative mortality was included. The overall 10-year survival rate(s.e.) was 77.3(3.7) per cent. Univariate analysis showed a significant difference in survival rates between cancers confined to the mucosa and those with submucosal invasion (P = 0.02), between patients with and without lymph node metastases (P = 0.05) and between those < or = 50 and > 50 years of age (P = 0.02). Using Cox multivariate analysis and a stepwise procedure for eight variables (sex, age, depth of invasion, lymph node metastases, presence of ulceration, location, histological type, type of surgery), age and histological type had the most significant effect on survival. Seven operative deaths were recorded. Eleven patients died from recurrent cancer and one is still alive with a gastric remnant recurrence. Other causes of death were metachronous primary cancer (six patients), cardiovascular disease (two), pneumonia (three), sepsis (one) and car accident (one). Although the prognosis of early gastric cancer is relatively good in western countries, patients should be carefully followed over a long period for late recurrence and for metachronous cancer, which has a high incidence.

Changing pattern of oesophageal cancer in a general hospital in the UK.

Reports in the literature indicate that there is a change in the pattern of oesophageal cancer. This prompted us to retrospectively examine 15 years of endoscopy records in this district general hospital to identify all patients with oesophageal cancer and to determine whether data from our area were similar to other reported series. Examination of 22,789 consecutive endoscopy records identified 199 oesophageal cancer cases. Overall 50% of these were adenocarcinomas, an even higher percentage than that reported in series based on cancer registry information. The number of squamous cell carcinomas in females was noted to be rising and this was associated with an increase in the age of female patients. Female patients were also significantly older than males. The cancer origins tended to be lower in the oesophagus in males than in females. These results support a rise in the percentage of oesophageal adenocarcinomas. Absolute numbers of cancers detected rose over the 15-year study, but this was in direct proportion to the number of endoscopies carried out annually and probably reflects an increased usage of endoscopy services during the period of study.

Effect of ascorbic acid on the intragastric environment in patients at increased risk of developing gastric cancer.

Ascorbic acid has been shown to decrease nitrosation in vivo, and epidemiological data suggest that the consumption of foods rich in this vitamin is associated with a reduced risk for gastric cancer. In order to study this suggestion further, fasting gastric juice samples were obtained from 62 high-risk patients (seven with atrophic gastritis, ten with pernicious anaemia, ten with partial gastrectomy, 21 with vagotomy and drainage and 14 with highly selective vagotomy), before, during four weeks' treatment with 1 g ascorbic acid four times daily, and four weeks after treatment. Samples were analysed for pH, total and nitrate-reducing bacterial counts, nitrite and N-nitroso compounds. Treatment with ascorbic acid lowered the median pH only in the vagotomized patients (p less than 0.001) but resulted in a reduction in median nitrate-reducing bacterial counts and in nitrite and N-nitroso compound concentrations in all groups, except for an increase in the nitrate-reducing bacterial count in atrophic gastritis patients and in nitrite in those with pernicious anaemia. These data suggest that treatment with a high dose of ascorbic acid reduces the intragastric formation of nitrite and N-nitroso compounds.

An enzyme-linked immunosorbent assay for the serodiagnosis of Campylobacter pylori-associated gastritis.

An ELISA system, using an acid extractable cell surface C. pylori antigen, has been used to detect anti-C. pylori antibodies in 176 endoscoped patients. The antibody concentration was related to histological diagnosis and colonisation with Campylobacter-like organisms. The criteria for sero-positivity was determined from the median antibody concentration in a group of 368 non-endoscoped control patients. The specificity and sensitivity of the sero-diagnostic assay for histological gastritis in antral biopsies was 83.0% and 95.6% respectively. The positive (79.3%) and negative predictive values (94.3%) indicate that such a sero-diagnostic assay could be used to screen patients prior to endoscopy.

Prevalence of Campylobacter pylori in duodenal and gastric mucosa--relationship to inflammation.

Endoscopic biopsies from 310 patients were studied for the presence of Campylobacter pylori (Cp). In the first group of 150 patients duodenal and antral biopsies were obtained and in the second (160 patients) biopsies were taken from various sites in the stomach including the antrum, incisura, body and fundus. In the duodenum there was a strong association with active inflammation and the presence of gastric metaplasia. Cp were never seen in the normal duodenum. In the stomach Cp presence was associated with gastritis irrespective of severity and site, but was absent in areas showing intestinal metaplasia. Cp were seen in histologically normal biopsies from all areas of the stomach but were significantly more common in normal fundal than normal antral mucosa.

Campylobacter like organisms in duodenal and antral endoscopic biopsies: relationship to inflammation.

In 66 endoscopic duodenal biopsies studied retrospectively and in 84 paired duodenal and antral biopsies assessed prospectively campylobacter like organisms were seen in 22 (33%) of the retrospectively examined duodenal biopsies and in 61 (73%) examined prospectively, and in 70 (83%) of antral biopsies. In the duodenum the organisms were mostly confined to the surface epithelium in areas showing gastric metaplasia, while in the antrum they were also found within superficial glands. A strong association was shown between the presence of campylobacter like organisms and histological active duodenal inflammation.

Dose-response curve analysis of gastric secretory responses in the dog and man to impromidine: a new histamine-H2-receptor agonist.

The new histamine-H2-receptor agonist, impromidine, was assessed for its effect on gastric acid secretion using a dose-response format. Maximal acid output and ED50 were calculated for infusions of impromidine in the Heidenhain pouch dog (0.05-1.6 x 10(-8) mol/kg/hr) and in man (0.39-6.22 x 10(-8) mol/kg/hr). Analysis of the responses was carried out by nonlinear regression using the logistic function. This allowed the data to be analyzed without making assumptions about the steepness of the curve which in man was almost twice that found in the dog (1.8:1). The ED50 in the dog was 0.26 +/- 0.029 x 10(-8) mol/kg/hr. The control dose-responses could be inhibited in a competitive manner by histamine-H2-receptor antagonists. Analysis of the control curve and three curves in the presence of increasing doses of antagonist was carried out by fitting all the curves simultaneously to calculate an in vivo ID50. In the dog, the antagonist was tiotidine (0.05, 0.1 and 0.2 x 10(-6) mol/kg/hr) and the ID50 was 0.012 +/- 0.002 x 10(-6) mol/kg/hr. In man, cimetidine (1.05, 2.10 and 4.2 x 10(-6) mol/kg/hr) was used to inhibit secretion. The calculated ID50 was 0.63 +/- 0.085 x 10(-6) mol/kg/hr. Comparison of the effect of cimetidine and tiotidine against both impromidine and histamine showed that the ID50 was the same for both stimulants. Impromidine proved to be a potent stimulant of gastric acid secretion acting via the H2-receptor to produce readily definable dose-response curves in the dog and in man.

Gastric acid secretion induced by impromidine in the dog and man: analysis of dose-response relationships.

The new histamine H2-receptor agonist, impromidine, was used to assess three models of dose-response curves in vivo. Vm and ED50 values were calculated for gastric acid output to infusions of impromidine in the dog with a Heidenhain pouch and in man. In two models Michaelis-Menten kinetics were assumed: the linear transformation using the Eadie-Hofstee plot and the non-linear hyperbola, but in the third method the logistic function allowed the data to be analysed without making assumptions about the steepness of the curves. In the dog all three models gave similar results both for calculated Vm and ED50. Curve steepness from the logistic function was found to be 0.98 +/- 0.023 - not different from that assumed for the hyperbola (where steepness = 1). The results in man were different: the Eadie-Hofstee plot did not produce a significantly linear fit while the logistic function produced the smallest standard errors. The logistic curve slope was almost twice that assumed for the hyperbola (1.8 : 1) and it seems, therefore, that impromidine-induced gastric acid secretion does not follow Michaelis-Menten kinetics in man and data should be analysed using methods which allow the calculation of curve steepness.

Gastric mucosal blood flow and acid secretory changes in man with impromidine: a new specific histamine-H2-receptor agonist.

The effect of impromidine, a new histamine-H2-receptor agonist, on gastric mucosal blood flow (neutral red clearance) and acid secretion was studied in nine volunteers. Impromidine stimulated a dose-dependent increase in neutral red clearance and acid secretion. Simultaneous cimetidine in three doses caused a parallel shift to the right for both acid output and clearance with unchanged maxima compatible with simple surmountable antagonism. There were small cardiovascular changes: an increased heart rate with a decreased diastolic pressure during infusion of impromidine. These changes were antagonised by cimetidine.