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.

An initial comparison of nine centres registering patients with the UK National Barrett's Oesophagus Registry (UKBOR).

Initial data from the first nine hospitals registering at least 50 patients each with UKBOR were analysed. This involved 2102 Barrett's oesophagus (BO) cases (M1261:F841), mean 234 patients per centre (range 73-636) and M:F ratio 1.5 (range 1.1-2.3). There was an equal geographical distribution of the hospitals, three each in the north of the country (N), Midlands (Mid) and the south of the country (S). The catchment populations varied from 145,000 to 450,000. The M:F ratio for N, Mid and S was 1.6, 1.3, 1.7, respectively. The mean age at diagnosis in males was 62.0 years (range 53.2-66.3) and in females 67.6 years (range 59.3-73.4), with little geographical variation. The age distribution varied somewhat between the centres; the peak age for males being 40-49 years in one northern hospital, 60-69 years in seven others and 70-79 years in one hospital. For females it was 60-69 years and 70-79 years in each of four hospitals, and 80-89 years in one. The BO diagnosis rate in the under 50s was fairly constant; F mean 14% (range 0-23%); M (eight centres) mean 23% (range 16-27%). However, in one northern centre it was much higher (43%). Information on patients with a diagnosis of oesophageal adenocarcinoma (AC) was available from seven centres. A total of 59 AC were diagnosed (M44:F15, ratio 2.9). The overall mean rate of AC in BO was 3.6% (range 0.5-7.5%). Minor variations in BO patient characteristics may have been due to the hospitals' different policies on diagnostic and reporting criteria. However, the much higher percentage of men under age 50 in the one N centre may reflect a genuine difference in diet and lifestyle, or possibly genetic susceptibility.

Effects of high dose vitamin C treatment on Helicobacter pylori infection and total vitamin C concentration in gastric juice.

Low gastric juice total vitamin C concentration in the presence of Helicobacter pylori (H. pylori) infection probably plays a role in gastric carcinogenesis. In vitro vitamin C has been shown to inhibit the growth of H. pylori. The aims of this study were to determine the effect of high dose vitamin C administration on H. pylori infection and on gastric juice total vitamin C concentration in patients with H. pylori related chronic gastritis. Sixty patients with dyspeptic symptoms and proven chronic gastritis and H. pylori infection, who were undergoing routine endoscopy, entered the study after giving informed consent. They were randomly coded into two treatment groups. Group 1 (controls, n = 28) were treated with antacids for 4 weeks and Group 2 (n = 32) received vitamin C 5g daily also for 4 weeks. Nine patients did not complete the study and were excluded. Plasma and gastric juice total vitamin C levels were measured at baseline, at the end of 4 weeks treatment and again 4 weeks after treatment cessation. In the control group H. pylori infection remained unchanged in all 24 patients throughout as did the mean gastric juice total vitamin C concentration. However, in the vitamin C treated group eight of 27 patients (30%) who completed the treatment course the H. pylori infection was eradicated (P = 0.01). In these patients the mean gastric juice total vitamin C concentration rose significantly from 7.2 +/- 1.6 micrograms/ml after 4 weeks treatment (P < M 0.001) and 19.8 micrograms/ml 4 weeks after treatment was discontinued (P < 0.001). In the remaining 19 patients with persistent H. pylori infection, the mean gastric juice total vitamin C concentration rose less than in those with successful H. pylori eradication; 6.3 +/- 1.7 micrograms/ml before treatment, 10.8 +/- 1.5 micrograms/ml after 4 weeks treatment (P < 0.05) and a return to pre-treatment levels (7.1 +/- 2.7 micrograms/ml) 4 weeks after vitamin C intake stopped. There were no side effects of vitamin C treatment. This study has shown that 4 weeks daily high dose vitamin C treatment in H. pylori infected patients with chronic gastritis resulted in apparent H. pylori eradication in 30% of those treated. In those patients there was also a highly significant rise in gastric juice total vitamin C concentration which persisted for at least 4 weeks after the treatment ceased. A significant, though less marked, gastric juice total vitamin C concentration increase was observed during vitamin C treatment even in subjects with persistent H. pylori infection, though this was not maintained after treatment ended. The mechanism whereby vitamin C treatment appeared to result in H. pylori eradication is unclear. Further confirmatory studies are indicated.

N-Nitroso compounds, bacteria, and carcinoembryonic antigen in the gastric stump.

Analyses of biochemical and microbiological parameters such as pH, N-nitroso compound (NOC) concentration, carcinoembryonic antigen (CEA) level, and total viable counts (TVCs), and identification of microorganisms were carried out on 65 fasting gastric juice samples obtained at endoscopy from 45 patients previously submitted to partial gastrectomy for benign peptic ulcer disease (23 Billroth I, 22 Billroth II/Reichel-Polya) and 20 normal controls. Biopsy specimens were taken to determine histology, the Helicobacter pylori status, and both tissue CEA immunoreactivity and level. Significantly higher mean pH values, NOC and CEA concentrations, and TVCs were found in partial gastrectomies compared with normal controls. In relation to surgical methods, higher mean pH values, NOC concentrations, TVCs, and anaerobic bacterial counts were observed in the juice of patients with Billroth II compared with Billroth I gastrectomies. Mild CEA immunoreactivity and apical CEA localization were found significantly more often in Billroth II than in Billroth I stumps. Intensive CEA immunoreactivity and cytoplasmatic localization were found significantly more often in Billroth I than in Billroth II stumps. Independent of the type of surgical reconstruction, higher mean NOC levels were recorded in patients with more severe histological changes and H. pylori infection. Higher mean CEA levels in gastric juice and tissue were detected in the gastric stumps with more severe histological changes. All these data suggest that high levels of NOCs in the gastric juice could be a cofactor in gastric stump carcinogenesis and determination of CEA level in gastric juice and tissue could be included as a very useful marker in quantifying this process.

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.

N-nitroso compounds in the gastric juice of normal controls, patients with partial gastrectomies, and gastric cancer patients.

BACKGROUND: It has been suggested that the variation of biochemical and microbiological parameters in the gastric juice may play a role in the development of gastric cancer. In the present study we concurrently assessed the presence of N-Nitroso compounds (NOC) and their precursors, bacteria and carcinoembryonic antigen (CEA) in the gastric juice of normal controls, patients with gastric resection, and advanced gastric cancer. METHODS: Detailed analyses of biochemical and microbiological parameters such as pH, nitrite (NO2) concentration, N-nitroso compounds (NOC) concentration, carcino-embryonic antigen (CEA) level, total viable counts (TVC), nitrate-reductase positive bacterial counts (NRPBC), and identification of micro-organisms were carried out. RESULTS: Significantly higher mean pH values, NO2, NOC and CEA concentrations, TVC, and NRPBC were found in partial gastrectomies compared with normal controls, and all these intragastric parameters were significantly higher in patients with gastric cancer than in those with partial gastrectomies. As far as surgical methods are concerned, higher mean pH values, NO2 and NOC concentrations, TVC, NRPBC, and anaerobic bacterial counts were observed in the juice of patients with Billroth II compared with Billroth I gastrectomies. Apart from the type of surgical reconstruction, higher mean NOC levels were recorded in patients with more severe histological changes and H. pylori infection. CONCLUSIONS: All these data suggest that the presence of high levels of NOC in the gastric juice of gastroresected patients can be considered a risk factor of gastric stump cancer.

Eradication of Helicobacter pylori and prevention of recurrence of duodenal ulcer: a randomized, double-blind, multi-centre trial of omeprazole with or without clarithromycin.

BACKGROUND: Antimicrobial treatment for Helicobacter pylori eradication is currently recommended for all patients with duodenal ulcer disease, but consensus on the best treatment is lacking. METHODS: Patients with active duodenal ulcer and H. pylori were enrolled in a double-blind, randomized, placebo-controlled multi-centre study. Patients received omeprazole 40 mg daily for 28 days and either clarithromycin 500 mg t.d.s. or placebo t.d.s. for the first 14 days. Patients underwent endoscopy before starting treatment, at 2 weeks, immediately after stopping treatment if unhealed at 2 weeks, and at 1, 6 and 12 months after the end of treatment, or at the recurrence of symptoms. Eradication of H. pylori, duodenal ulcer healing and ulcer recurrence were measured. RESULTS: One-hundred and fifty-four patients were recruited and randomized to omeprazole plus clarithromycin (n = 74) or to omeprazole plus placebo (n = 80). One month after treatment, H. pylori was eradicated in 57 of 69 (83%; 95% CI: 72-91%) patients receiving omeprazole plus clarithromycin, compared with 1 of 75 (1%; 95% CI: 0-7%) receiving omeprazole alone (P < 0.001). In patients receiving omeprazole plus clarithromycin the ulcer healed at 2 weeks in 83% (95% CI: 71-91%) and at 4 weeks in 100% (95% CI: 95-100%), compared with 77% (95% CI: 66-86%) and 97% (95% CI: 91-100%) in those given omeprazole plus placebo (N.S.). Ulcers recurred at 12 months in 6% (95% CI: 1-16%) of patients given omeprazole plus clarithromycin, compared with 76% (95% CI: 63-86%) of patients given omeprazole plus placebo (P < 0.001). The incidence of side-effects was similar in both treatment groups (38% with clarithromycin dual therapy and 29% with omeprazole plus placebo; P = 0.304). Ninety per cent of patients took at least 90% of their prescribed medication. CONCLUSIONS: Omeprazole plus clarithromycin dual therapy eradicated H. pylori in 83% of patients with duodenal ulcer and significantly decreased 12-month recurrence from 76% to 6%.

N-nitroso compounds in fresh gastric juice and their relation to intragastric pH and nitrite employing an improved analytical method.

In order to examine further the relationship between intragastric N-nitrosation, gastric pH and nitrite, 457 fresh, fasting gastric juice samples were analysed for total N-nitroso compounds (NOC) and nitrite concentrations using a recently described improved assay method. Nitrite in log values was linearly related to intragastric pH (r = 0.887, P < 0.01) with a regression equation log[nitrite] (mumol/l) = 0.489 x pH - 2.209. Significantly higher NOC concentrations were found at intragastric pH ranges of 1.13-2.99 (mean +/- SE: 1.45 +/- 0.17 mumol/l, P < 0.05) and 6.00-8.42 (3.57 +/- 0.33 mumol/l, P < 0.01) compared with that at pH 3.00-5.99 (1.02 +/- 0.12 mumol/l). NOC concentration was significantly related to log nitrite concentration at both the low pH range 1.13-4.99 (r = 0.169, P < 0.01) and the high pH range 5.00-8.42 (r = 0.450, P < 0.01). The results in the present study confirm that both acid-catalysed N-nitrosation and biologically-catalysed N-nitrosation occur in the human stomach. However, great variations in nitrite and NOC concentrations were observed in both low and high pH samples, indicating that, as expected, both the acid-catalysed N-nitrosation and biologically-catalysed N-nitrosation processes are markedly affected by factors other than intragastric pH and nitrite.