Gastric cancers in Finnish patients after cure of Helicobacter pylori infection: A cohort study.

Helicobacter pylori infection is associated with gastric cancer. A total of 97% of the infected subjects have elevated levels of H. pylori antibodies. The antibody titers have been shown to decline rapidly (40-60% within 4-12 months) only after successful eradication therapy. We allocated 26,700 consecutive patients tested during 1986-1998 for H. pylori antibodies to 3 subcohorts: seropositive patients with rapidly falling antibody titers (Hp+CURED, n = 3,650), seropositive patients where no serological information indicating cure was obtained (Hp+NoInfo, n = 11,638) and seronegative patients (Hp-, n = 11,422). In the subcohorts, the standardised incidence ratios (SIRs) with 95% confidence intervals (CI) were defined for subsequent cancers of stomach, pancreas, colon, rectum, breast and prostate separately and for all cancers except stomach combined. The mean follow-up time was 10.1 years and the number of gastric cancers was 72. For the Hp+CURED, the SIR for gastric cancers for the first 5 follow-up years was 1.62 but decreased from the sixth follow-up year thereon to 0.14 (CI: 0.00-0.75). Likewise, the risk ratio, defined in a Poisson regression analysis using the Hp+NoInfo group as the reference, decreased from 1.60 to 0.13 (CI: 0.02-1.00, p = 0.049). The SIR for Hp- was not significantly higher than that for Hp+NoInfo for any of the cancers analysed. To conclude, cured H. pylori infection led to a significantly decreased incidence of gastric cancers from the sixth follow-up year. Advanced atrophic gastritis would be a plausible contributor to the elevated SIR in elderly Hp- patients.

Development of a new method to get a reliable powder flow characteristics using only 1 to 2 g of powder.

In powder technology, it is often important to directly measure real powder flow rate from a small amount of powder. For example, in pharmaceutical industry, a frequent problem is to determine powder flow properties of new active pharmaceutical ingredient (API) in an early stage of the development when the amount of API is limited. The purpose of this paper is to introduce a new direct method to measure powder flow when the material is poorly flowing (cohesive) and the amount of material is about 1 to 2 g. The measuring system was simple, consisting of a flow chamber and electronic balance and an automated optical detection system, and for each measurement, only 1 to 2 g of sample was required. Based on the results obtained with this testing method, three selected sugar excipients, three grades of microcrystalline cellulose, and APIs (caffeine, carbamazepine, and paracetamol) can be classified as freely flowing, intermediate flowing, and poorly flowing powders, respectively. The average relative standard deviation for the flow time determinations was not more than 2-10%. The present novel flowability testing method provides a new tool for a rapid determination of flowing characteristics of powders (e.g., inhalation powders) and granules at a small scale.

A new rapid on-line imaging method to determine particle size distribution of granules.

The purpose of this research was to study the feasibility of the new image analysis method in the particle size determination of the granules. The method is capable of forming a three-dimensional topographic image of a sample surface from a digital picture. In the method, a flat granule bed surface was illuminated from three different directions, using the three primary colors (red, green, and blue). One color picture was taken by a digital camera, after which a topographic image of the object surface was constructed. The particle size distribution was then calculated from the image data. The particle size analysis method was tested both off-line and on-line. Off-line particle size measurement results determined by the image analysis method corresponded quite well to those of sieve analysis in the size fraction range 250-1,000 microm. In on-line application, images were successfully retrieved and median granule size trend could be calculated and followed during fluid bed granulations.

Size of the peptic ulcer in Helicobacter pylori-positive patients: association with the clinical and histological characteristics.

OBJECTIVE: Based on a large trial of Helicobacter pylori-positive peptic ulcer patients, we studied whether the size of the ulcer, along with other clinical and histological characteristics, has any effect on healing. We also studied the clinical and endoscopic characteristics associated with size of the peptic ulcer. MATERIAL AND METHODS: A total of 333 consecutive patients with H. pylori infection and peptic ulcer were enrolled (mean age 54.8+/-12.7 years). Location of the ulcer was recorded by gastroscopy and the presence of H. pylori was assured by rapid urease test, histology and by serum H. pylori IgG and IgA antibody measurement. The diameter of the ulcer was measured by placing the opened biopsy forceps (7 mm) beside it. Biopsy specimens were examined in accordance with the Sydney system. RESULTS: Mean size of the peptic ulcer was 13.2+/-8.3 in corpus, 11.3+/-5.3 in antrum, 13.8+/-7.8 in angulus, 9.5+/-5.3 in prepylorus and 9.2+/-4.7 mm in duodenum (duodenal versus gastric type; p<0.05). Average size of the ulcers was 9.4+/-5.3 mm in patients with Forrest III type and 11.5+/-6.8 in other types (p<0.05). Patients who were >or=50 years of age, currently smoking, or who had corpus-predominant chronic gastritis or atrophic gastritis, had larger ulcers than others. Size of index ulcers, successful eradication of H. pylori and the presence of atrophic gastritis were independent factors for healing. The odds ratio was 11.5 (95% CI 3.3-40.5; p<0.01) for eradication of H. pylori, 3.5 (95% CI 1.1-11.2; p<0.05) for size of the index ulcer (10 mm) and 3.4 (95% CI 1.2-9.8; p<0.05) for atrophic gastritis versus no atrophy. CONCLUSIONS: Size of the peptic ulcer, successful H. pylori eradication and atrophic gastritis were independent factors for the healing of peptic ulcers. A number of clinical and endoscopic variables (age, current smoking, corpus-predominant gastritis, Forrest classification) were associated with size of the peptic ulcer in H. pylori-positive patients.

Clinical significance of widespread gastric metaplasia in the duodenal bulb.

BACKGROUND: All the risk factors of peptic ulcer disease are not thoroughly understood. GOALS: To assess duodenal gastric metaplasia (DGM) in relation to Helicobacter pylori status and endoscopy findings with special reference to the effects of highly selective vagotomy. STUDY: The study population consisted of 1056 adult patients and an additional 154 patients who had had a highly selective vagotomy. Their clinical and endoscopy records as well as the histology of gastric and duodenal biopsies were evaluated retrospectively. H. pylori infection had been determined by serology and culture. RESULTS: Widespread (more than 20%) DGM was strongly associated with H. pylori positive duodenal ulcer disease (in 59.7% of patients). The prevalence of DGM diminished progressively the more proximally the ulcer was located in the stomach, and was 2.5% in proximal gastric ulcers patients. In vagotomized patients, the prevalence of widespread DGM (8.4% of patients, median 14 years after operation and the majority still H. pylori positive) was close to that of patients with H. pylori gastritis without peptic ulcer disease (4.5%). CONCLUSIONS: Widespread DGM is an indicator for an increased risk of duodenal ulcer among H. pylori positive patients and it could be used to select patients for eradication therapy.

Helicobacter pylori eradication in the healing of atrophic gastritis: a one-year prospective study.

OBJECTIVE: Whether gastric atrophy or intestinal metaplasia heals after successful treatment of Helicobacter pylori (H. pylori) infection is still a matter of controversy. The aim of this article was to clarify whether, after one year, H. pylori eradication is associated with healing in glandular atrophy and intestinal metaplasia in the corpus and antrum. MATERIAL AND METHODS: Ninety-two H. pylori-positive peptic ulcer patients with atrophic gastritis (panatrophy, antral or corpus predominant) participated in the baseline study, 1-year prospective follow-up data being available from 76 patients. Mean age was 58+/-12.6 years (mean+/-SD) and the male/female ratio 2/1. The patients participated in an H. pylori eradication study in which they randomly received active eradication therapy. Endoscopy was performed before H. pylori eradication therapy and after 8 and 52 weeks, with specimens examined according to the Sydney system. RESULTS: Of the 92 patients, 8 (9%) had panatrophy, 58 (63%) had antral- and 26 (28%) had corpus-predominant atrophic gastritis. After H. pylori eradication, the mean atrophy score declined in patients with antral-predominant atrophy from 1.5 (mean) to 0.7 (p<0.05), in corpus-predominant atrophy from 1.7 to 0.2 (p=NS) and in patients with panatrophy from 1.2 to 0.8 (p=NS). Atrophy healing was seen in 55% of antral-predominant atrophy patients who had successful H. pylori eradication. The mean antral atrophic score in one year declined in patients with duodenal ulcer (from 1.0 mean to 0.4) whereas it remained the same (1.3) in those with gastric ulcer (p<0.05). CONCLUSIONS: Atrophy can diminish or even disappear, especially in the antrum, during a 1-year follow-up after eradication of infection. Atrophy progression seems milder in patients with duodenal ulcer than in patients with gastric ulcer.

Helicobacter pylori eradication as the sole treatment for gastric and duodenal ulcers.

OBJECTIVES: It is uncertain whether eradication of Helicobacter pylori--without a prolonged suppression of acid secretion--is sufficient to allow healing of peptic ulcers. We evaluated whether eradication of H. pylori with no following anti-secretory medication then administered is sufficient for treatment of peptic ulcers. We also looked at the impact of non-steroidal anti-inflammatory drug (NSAID) and acetylsalicylic acid (ASA) use on ulcer relapses. METHODS: The effect of eradication on ulcer healing and relapse rate was analysed in 115 patients, randomly allocated to four treatment groups: (1) quadruple therapy (28); (2) dual therapy (n-30); (3) triple therapy (n=27); and (4) lansoprazole and placebo (n=30). Endoscopic assessment was performed at 0, 8, and 52 weeks. RESULTS: The ulcer healing rate was 100% [95% confidence interval (CI), 95-100%] in H. pylori-negative and 83% (95% CI, 67-94%) in H. pylori-positive patients (P<0.01). In patients who used NSAIDS or ASA, the healing rates was 100% (95% CI, 73-100%) and 75% (95% CI, 19-99%) in H. pylori-negative (12 patients) and H. pylori-positive patients (four patients) (P = not significant). Ulcer relapses occurred in 5% (95% CI, 1-13%) of H. pylori-negative and in 36% (95% CI, 19-56%) of H. pylori-positive patients (P < 0.01). In H. pylori-negative patients who used NSAIDs or ASA the ulcer relapse rate was 30% (95% CI, 7-65%), whereas the ulcer relapse rate was 2% (95% CI, 0.4-10%) in patients who did not use NSAIDs or ASA (P < 0.05). No difference in ulcer relapse rate in H. pylori-positive patients who used or did not use NSAIDs or ASA was found. The eradication rate of H. pylori was 93% (95% CI, 76-99%) in the quadruple therapy group, 83% (95% CI, 64-94%) in the dual therapy group, 100% (95% CI, 87-100%) in the triple therapy group, and 0% (95% CI, 0-12%) in the lansoprazole and placebo group. CONCLUSIONS: Eradication treatment for H. pylori-positive gastric or duodenal ulcer is sufficient, with no need to follow it with anti-secretory medication. Cure of the infection reduces ulcer relapses in patients who did not use NSAIDs or ASA.

Association of Helicobacter pylori IgA antibodies with the risk of peptic ulcer disease and gastric cancer.

AIM: To compare the prevalence of Helicobacter pylori (H pylori) IgG and IgA antibodies between adult subjects, with defined gastric diseases, non-defined gastric disorders and those representing the population. METHODS: Data on H pylori IgG and IgA antibodies, determined by enzyme immunoassay, were analyzed in 3,252 subjects with DGD including 482 patients with gastric ulcer, 882 patients with duodenal ulcer, 1,525 patients with chronic gastritis only and 363 subjects with subsequent gastric cancer, 19,145 patients with NoDg and 4,854 POPUL subjects. The age-adjusted prevalences were calculated for 1- and 20-year age cohorts. RESULTS: The prevalences of IgG antibodies were equally high (89-96%) in all 20-year age cohorts of the DGD groups, whereas the prevalences of IgG antibodies were lower and increased by age in the POPUL and NoDg groups. The prevalences of IgA antibodies were also higher in the DGD groups; among them CA (84-89%) and GU groups (78-91%) showed significantly higher prevalences than DU (68-77%) and CG patients (59-74%) (OR 2.49, 95%CI 1.86-3.34 between the GU and DU groups). In the CA, GU, and DU groups, the IgA prevalences showed only minor variation according to age, while they increased by age in the CG, POPUL, and NoDg groups (P<=0.0001). The IgA response, but not the IgG response, was associated with an increased risk of CA (OR 2.41, 95%CI 1.79-3.53) and GU (OR 2.57, 95%CI 1.95-3.39) in comparison with CG patients. CONCLUSION: An IgA antibody response during H pylori infection is significantly more common in CA and GU patients as compared with CG patients.

Eradication of Helicobacter pylori improves the healing rate and reduces the relapse rate of nonbleeding ulcers in patients with bleeding peptic ulcer.

OBJECTIVE: A causal relationship between Helicobacter pylori (H. pylori) and peptic ulcer complications remains obscure. The aim of this study was to determine the importance of H. pylori and other risk factors for healing rate, ulcer recurrence, and rebleeding in patients with bleeding peptic ulcer. METHOD: A total of 223 patients with H. pylori positive bleeding peptic ulcer were randomly allocated to three treatment groups: 1) quadruple therapy (QT) (88 patients); 2) dual therapy (DT) (88 patients); and 3) omeprazole and placebo therapy (OPl) (47 patients). Endoscopic assessment was performed initially and at 8 and 52 wk. Ulcer healing and eradication rates were assessed; endpoints were ulcer relapse and ulcer rebleeding during 52 wk. RESULTS: Results after 8 and 52 wk were available for 211 and 179 patients, respectively. Eradication rate was 100% (95% CI = 96-100%) in the QT, 84% (95% CI = 74-91%) in the DT, and 4% (95% CI = 1-15%) in the OPl group. Ulcer healing rate was 95% (95% CI = 91-98%) in H. pylori negative and 8% (95% CI = 70-91%) in H. pylori positive patients. Ulcer relapses occurred in 2% (95% CI = 0.5-6%) of H. pylori negative and in 38% (95% CI = 24-54%) of H. pylori positive patients, and rebleeding occurred in five patients (three H. pylori positive and two negative). CONCLUSIONS: Eradication of H. pylori infection enhances healing of bleeding peptic ulcers after endoscopic therapy. H. pylori infection is an important independent risk factor for relapsing of nonbleeding ulcers in patients with bleeding peptic ulcer.