Helicobacter pylori and NSAID-induced gastric ulcer in a Japanese population.

A recent meta-analysis by Huang et al. clarified that Helicobacter pylori infection and nonsteroidal antiinflammatory drugs (NSAIDs) are important factors for peptic ulcer. The results showed that the risk for ulcer in NSAID(+)/H. pylori(+) patients was 61.1 fold higher when compared with NSAID(-)/H. pylori(-) patients. Some gastric ulcers detected in patients on NSAID therapy may actually be caused by H. pylori, but it is difficult to differentiate NSAID-induced gastric ulcer from H. pylori-induced gastric ulcer. Several studies have investigated the effects of H. pylori eradication on ulcer healing. One study reported that H. pylori eradication actually lowered the healing rate of gastric ulcers. Because there have been no studies finding that H. pylori eradication facilitates healing, H. pylori eradication is not recommended for NSAID users. Concerning the efficacy of H. pylori eradication in the prevention of NSAID-induced gastric ulcer, a meta-analysis concluded that among all patients on NSAID therapy, H. pylori eradication lowered the prevalence of ulcer, which was particularly marked in NSAID-naïve patients. When compared with those of proton pump inhibitors (PPIs), the preventative effects of H. pylori eradication were inferior. In Japan, national health insurance does not cover procedures that prevent or lower the risk for NSAID-induced ulcer. When administering NSAID to patients with risk factors, it is desirable to administer antiulcer agents.

Assessment of co-existence of Helicobacter pylori and Candida fungi in diseases of the upper gastrointestinal tract.

Candida spp. were found in the gastric mucosa of 27 (17%) patients, out of whom 18 (11%) showed co-existence of the fungi with H. pylori. Analysis of relationship between selected disorders of the upper gastrointestinal tract (non ulcer dyspepsia NUD, gastric ulcer, duodenal ulcer) and infection with H. pylori and/or Candida revealed a link between co-existence of H. pylori with Candida and gastric ulcers suggesting synergism of those microorganism in pathogenesis of the disease. On the contrary, according to quantitative studies performed, the fungi alone do not play a significant role in pathogenesis of the above mentioned disorders as they colonize only epithelium to the extent that is not pathologically significant (<10(3) CFU/ml). Genetical study was carried out on 57 Helicobacter pylori strains isolated from bioptates of the gastric mucosa. The genotypes of the strains (gene cagA and alleles of gene vacA - m1, m2, s1, s2) were determined using the PCR technique. As it was shown, the patients infected with H. pylori strains of genotype cagA+, vacA s1 are exposed to higher risk of peptic ulcer disease (PUD) as compared to the patients infected with cagA-, vacA s2 strains. In the case of the NUD patients a correlation with allele m2 was found only (p<0.001). This may suggest that in future some of the NUD patients infected with cagA+, vacA s1 strains will fall into the group at higher risk for PUD.

[Assessment of rate of hydroxyl anions production by Helicobacter pylori in stomach].

Production of hydroxyl anions by tissue samples of pylorus mucous membrane obtained from 45 patients with gastric or duodenal ulcers was investigated. The production was estimated using the recently developed method based on measurement of rate of pH change in urea-containing reaction mixture. The rate of [OH-] generation as a result of H. pylori metabolism accounted on pylorus square varied from 0.4 to 1318.9 mcmol [OH-]/min, and in 90.2% of cases it did not exceed 128.1 mcmol [OH-]/min. This rate is comparable to mean rate of [H+] generation in stomach of healthy man--114.2-238.4 mcmol [H+]/min. Obtained results allow to conclude that this bacterium may participate in regulation of stomach acid-base balance.

Duplicate breath testing to confirm eradication of Helicobacter pylori: incremental benefit and cost in 419 patients.

BACKGROUND: Current standards for establishing a cure of H. pylori infection require two breath tests taken at least 4 weeks apart, to be negative. AIM: To determine the incremental cost and accuracy of repeating a urea breath test (UBT) in clinical practice. METHODS: We identified 419 patients with documented Helicobacter pylori infection who received eradication therapy and then had two breath tests, one 4 weeks and the second at least 8 weeks after the completion of treatment. H. pylori infection was documented at baseline by a positive rapid urease test and histology. RESULTS: In patients with successful eradication of H. pylori infection (n = 317), the mean +/- standard deviation delta over baseline (DOB) value before treatment was 43 +/- 29 ppm. Following treatment, the mean DOB in cured was 0.56 +/- 2.1 ppm at 1 month and was similar to the value obtained at the second breath (0.68 +/- 1; P = 0.39), which was performed 60 +/- 71 days after the first UBT. In patients remaining infected (n = 102), the mean DOB at baseline was 47 +/- 20 ppm. Four weeks after treatment, the DOB was 40 +/- 32 ppm. The second UBT was performed 94 +/- 72 days after the first and the DOB was significantly greater than the first (47 +/- 28; P = 0.040). There was no discordant result between the first breath test and second breath test. At a cost of 30 euros/breath test, the incremental cost of a second breath test was 12 570 euros in this cohort with no incremental clinical benefit. CONCLUSIONS: A single UBT, 4 weeks after treatment is as effective as two serial breath tests in confirming H. pylori eradication. The incremental cost of the second breath test is very high with no incremental clinical benefit.

[Urease test of the gastric content deposits for diagnosis of Helicobacter pylori infection in the gastric mucosa].

A rapid urease test was applied to the examination of the deposit of gastric juice for diagnosing H. pylori in the gastric mucosa. Two hundred and twenty patients blindly randomized were examined in a case control study. The standard rapid urease test kit Jatrox-H.p.-Test (Rohm Pharma, Germany) was used to determine urease activity in the deposit of gastric juice and duodenal [n = 110 (Group 1)] and gastroduodenal [n = 110 (Group 2)] mucosae. Giemsa staining was employed as a comparison method to examine H. pylori infection in the gastric and duodenal mucosae. The availability of regions of duodenal metaplasia was confirmed by periodic acid-Schiff and alcian blue (Serva) staining tests (pH 1.0 and 2.5, respectively). The results of evaluation of the efficiency of the rapid urease test of gastric juice deposit and gastric and duodenal mucosae in Groups 1 and 2 were as follows: sensitivity (SE) (0.97, 0.99, 0,96), specificity (SP) (0.97, 0.97, 0.99), prevalence (0.64, 0.67, 0.24), test accuracy (TA) (0.96, 0.98, 0.98), negative (0.95, 0.97, 0.99) and positive (0.98, 0.99, 0.96) predictive values; positive (38.8, 33.0, 96.0) and negative (0.03, 0.01, 0.04) likelihood ratios. It is expedient to employ the rapid urease test for the diagnosis of H. pylori infection in the stomach (Se 96-99%, Sp 97%, TA 97-98%). When the test of gastric juice deposit and gastric biopsy is positive, the probability of gastric H. pylori availability is 98-99%. When the test is negative (the probability of H. pylori absence is 95-97%), duodenal biopsy is made. When the test of duodenal biopsy is positive, the probability of H. pylori availability is 96%. When it is negative, the probability of H. pylori absence is 99%. An algorithm of use of the rapid urease test to diagnose H. pylori in different intestinal parts (stomach, duodenum) has been developed.

Application of a stool antigen test to evaluate the incidence of Helicobacter pylori infection in children and adolescents from Tehran, Iran.

Helicobacter pylori infection is acquired mainly in childhood, especially in developing countries, where a low-cost, rapid diagnostic technique which is reliable for all age groups may be useful for the management of H. pylori infection. For this purpose, we used an HpSA test (Equipar) to detect H. pylori infection in children and adolescents from Tehran, Iran. Thirty-five children who were positive or negative for H. pylori infection by endoscopy-based tests were used as positive and negative controls for the HpSA test. Stools were collected from 430 randomly selected children and adolescents (4 to 18 years old) from southwest, near the center, and northwest of Tehran. A questionnaire that included presence of recurrent abdominal pain (RAP), family history of infection and/or peptic ulcer disease (PUD), and income of parents was completed. A good agreement was found between the results of endoscopy-based tests and those of the HpSA test; the sensitivity and specificity of the Equipar-HpSA test were 100% and 83.4%, respectively. Among 430 children and adolescents, 47% were positive by the HpSA test, of whom 82% had RAP. No difference in incidence was observed between the two sexes; the various categories of age showed an increasing incidence, ranging from 24% (ages 4 to 6) to 58% (ages 16 to 18). The rate of infection in children and adolescents from the southwest was significantly higher (70%) than the rate in those from the northwest (32%), and a family history of H. pylori infection or PUD was observed in 59% of the HpSA positive subjects. The HpSA test is a useful test to detect H. pylori infection in children and adolescents from developing countries.

Upper GI risks of NSAIDs and antiplatelet agents: key issues for the cardiologist.

The use of antiplatelet/antithrombotic agents (eg, low-dose aspirin or clopidogrel) in primary or secondary intervention treatment strategies for cardiovascular disease is a common practice among cardiologists. Furthermore, these agents frequently are used concomitantly with other nonsteroidal anti-inflammatory drugs (NSAIDs) that patients are taking for a wide array of rheumatologic- or orthopedic-related complaints. These therapies, however, have defined upper gastrointestinal (UGI) risks for ulcer-related injury and complications. It is important for the cardiologist to fully understand the UGI risk profiles so that each patient is evaluated as a candidate for possible preventive co-therapy with appropriate anti-ulcer medication.

Does Helicobacter pylori infection explain all socio-economic differences in peptic ulcer incidence? Genetic and psychosocial markers for incident peptic ulcer disease in a large cohort of Danish adults.

BACKGROUND: Peptic ulcer epidemiology has changed considerably within the past century. The aim of this study was to assess the 11-year cumulative incidence of peptic ulcer disease and examine the relationship between ulcer incidence and psychosocial and genetic factors. METHODS: A random sample of 2416 Danish adults with no history of peptic ulcer disease residing in Copenhagen County, Denmark, attended a population-based prospective cohort study in 1983 and 1994. All participants reported whether they had had an ulcer diagnosed within the observation period. Information on socio-economic factors, family history of peptic ulcer disease (PUD) and lifestyle practices was obtained from a questionnaire. Lewis blood group antigens were assessed from blood samples and Helicobacter pylori infection status was determined with an in-house IgG ELISA. RESULTS: The overall 11-year cumulative incidence proportion of PUD was 2.9% (95% CI (2.2; 3.6)), i.e. 1.6% (95% CI (1.1; 2.1)) for duodenal ulcer, and 1.3% (95% CI (0.8; 1.7)) for gastric ulcer. Poor socio-economic status increased the risk of PUD independently of H. pylori infection (odds ratio 2.7, 95% CI (1.1; 6.1)) and accounted for 17% of all ulcer cases. High physical activity at work increased the risk of PUD in people infected with H. pylori (odds ratio 2.6, 95% CI (0.8; 8.0)). Family history of PUD or Lewis blood group antigens did not relate to ulcer incidence. CONCLUSIONS: Poor socio-economic status is an important risk factor for PUD that exerts its effect independently of H. pylori infection. Strenuous work may increase the risk of PUD in people with H. pylori infection. Genetic factors do not influence the risk of PUD in Danish adults.

Does seropositivity for Helicobacter pylori antibodies increase outpatient costs for gastric and duodenal ulcer or inflammation?

BACKGROUND: Helicobacter pylori is regarded as an important cause of both peptic ulcer and chronic gastritis. In particular, seropositivity is highest in patients with duodenal ulcer. No studies have determined whether there are differences in the direct medical costs associated with gastric/duodenal ulcer or inflammation, between seropositive and seronegative patients. OBJECTIVE: To examine the relationship between seropositivity for H. pylori and outpatient visits and direct medical costs for gastric/duodenal ulcer or inflammation in Japan from the perspective of the payor and patients. METHODS: Participants were males (n = 653) who worked for an agricultural co-operative in Fukuoka Prefecture, attended an annual health examination (including a written lifestyle and medical survey), belonged to the same health insurance society consistently for 4 years from April 1996 to March 2000, and provided a blood sample. The survey asked about lifestyle, including smoking and drinking, and past medical history. We retrospectively analysed the annual number of outpatient visits per person and outpatient medical cost (Yen, 2000 values) per person for visits relating to gastric or duodenal ulcer or inflammation using International Classification of Diseases (9th edition) -- Clinical Modification codes. We assessed for potential confounding factors using analysis of covariance and the chi-square test. RESULTS: The annual outpatient incidence of disease, the number of visits to physicians, and the medical costs for gastric or duodenal ulcer or inflammation were about 2-fold greater in individuals with antibodies to H. pylori compared with those without antibodies. CONCLUSION: Population-based studies and/or randomised controlled clinical trials that target high-risk groups and account for the unique way in which data are collected in Japan are needed to determine whether medical costs for gastric and duodenal ulcer might be reduced by treating asymptomatic patients who have antibodies to H. pylori.

[Changes in the prevalence of H. pylori in Perú; during the 1985-2002 period in medium and upper socio-economic strata]. / Variacion de la prevalencia del H. pylori en le Perú período (1985-2002), en una población de nivel socioeconómico medio y alto.

INTRODUCTION: In the developed countries, the prevalence of infection by H. Pylori among patients with active chronic gastritis (ACG) and peptic ulcer is diminishing. In developing countries, as far as it is known, neither a time variation of this infection nor a related epidemiological phenomena have been reported. OBJECTIVE: Determine the changes in the prevalence of H. pylori in patients from medium and high socio-economic strata in Lima, with ACG and peptic ulcer from 1985 to 2002. MATERIAL AND METHODS: An evaluation by means of an esophago-gastroduodenoscopy was carried out in a private hospital in 1,815 patients from the medium and upper socio-economic strata, all of them residents in Lima, Peru and showing upper gastrointestinal tract symptoms. Coloring with hematoxilin-eosin was used. RESULTS: 1,260 patients with ACG were identified: 178 with duodenal ulcer, 55 with gastric ulcer and 292 with histologically normal gastric mucose (HNGM). Prevalence of H. pylori among patients with ACG dropped from 83.3% to 58.7% (p<0.001) in males and females under 30 years old and from 31 to 50 years old (p=0.001). In patients with duodenal ulcer it decreased from 89.5% to 71.9% (p=0.004) and in those patients with gastric ulcer, from 84.8% to 77.3% (p=0.36). In patients with HNGM, prevalence remained the same (from 2.7% to 0.0%) (p=0.15). CONCLUSIONS: Between 1985 and 2002, in Lima, Peru, H. pylori prevalence in patients from the medium and upper socio-economic strata, with ACG and peptic ulcer, diminished.

Evaluation of endoscopic 13C-urea breath test for assessment of Helicobacter pylori eradication.

To minimize the inaccuracies of the diagnostic methods for Helicobacter pylori infection, we developed a new diagnostic method and called it the endoscopic 13C-urea breath test (EUBT). We evaluated the accuracy of EUBT for detecting this infection and assessing its eradication. EUBT was conducted on 267 patients with gastroduodenal disease. After the collection of a baseline breath sample, gastroduodenal endoscopy was performed. A 20-ml aliquot of a solution containing 100 mg of 13C-urea was sprayed over the entire gastric mucosa via the endoscope. A breath sample was then collected 15 min after spraying. The content of 13CO2 was measured in the breath samples by ratio mass spectrometry. Two biopsy specimens each from the antrum and the middle corpus were obtained for culture and histology. The EUBT cutoff level was 1.4%. The sensitivity and specificity of EUBT for the diagnosis of H. pylori infection were both 98.2%, and for assessment of the eradication they were 100% and 98.9%, respectively. EUBT is an accurate method not only for the diagnosis of H. pylori infection but also for assessment of its eradication.

[Post-treatment assessment of Helicobacter pylori eradication, by polymerase chain reaction in gastric biopsies]. / Evaluación de la erradicación postratamiento del Helicobacter pylori por reaccion en cadena de la polimerasa en biopsias gástricas.

BACKGROUND: The pre-treatment detection of H.p. in the stomach of patients is easily achieved with routine methods. Conversely, with conventional methods, it is difficult to detect the presence of H.p. after treatment. OBJECTIVE: To estimate the actual percentage of successfully treated patients by using a more sensitive and specific technique (PCR) in the same biopsies where standard methods were negative for H.p. MATERIALS AND METHODS: We selected 97 treated patients (31 Gastric Ulcers/66 Duodenal Ulcers, 62 male/35 female, age: 49 +/- 14 years), in whom success of treatment was defined by histological means and CLO Test. In the same gastric biopsies H.p-DNA PCR was performed. Different therapeutic schemes were utilized, but all included Proton Pump Inhibitors + ATB. Eight weeks after the end of the treatment, without medication, the patients were controlled as follows: 5 biopsies per patient, 2 of antrum, 2 of corpus (in different zones) and 1 for CLO Test. H.p. eradication was defined on histological grounds (gastric biopsy histology: 10% formaldehide buffer fixation, paraffin inclusion, Giemsa, HE staining and inmunohistochemistry), CLO Test (Delta West Pty. Ltd. Bentley, Australia) and by the absence of H.p.-DNA by PCR (amplification of a 296 bp of the species-specific antigen of H.p. and visualization of the amplified product in agarose gel with Ethidium Bromide and UV light). RESULTS: [table: see text] CONCLUSIONS: The higher sensitivity of PCR (10(3) fold more than conventional methods) allowed us in this group of patients to detect 13% of false eradication. It would be necessary to follow up this group of patients in order to know whether they develop or not clinical symptoms and/or histological evidence of disease. If such a case PCR could become an important tool for treatment evaluation.

Assessment of a new triple agent regimen for the eradication of Helicobacter pylori and the nature of H. pylori resistance to this therapy in Japan.

BACKGROUND: Multiple regimens for the eradication of Helicobacter pylori have been tested, but the best therapy has not been determined yet. To determine the efficacy of a new triple agent regimen using a combination of lansoprazole, amoxicillin, and clarithromycin against Helicobacter pylori (H. pylori), and to examine H. pylori resistance to this therapy in ineffective cases. METHODS: We studied a total of 71 patients infected with H. pylori who had gastric ulcer (n = 37) or duodenal ulcer (n = 34) as confirmed by endoscopy. Patients received 1500 mg amoxicillin, 400 mg clarithromycin and 30 mg lansoprazole for 2 weeks followed by 30 mg lansoprazole for 6 weeks in patients with gastric ulcer or for 4 weeks in those with duodenal ulcer. Endoscopic examination was performed before treatment and at 1 month, 2 months, and 5 months after initiating treatment to check the status of ulceration and H. pylori infection. RESULTS: The eradication rate of H. pylori was 92% (CI, 83-100%) in the gastric ulcer group and 94% (CI, 86-100%) in the duodenal ulcer group at 5 months, as determined by per-protocol analysis. Resistance to clarithromycin was present in 1 of 71 (1%) patients before treatment and in 2 of 5 (40%) patients after treatment. No resistance to amoxicillin and lansoprazole was found in patients before or after treatment. The resistance to clarithromycin changed during the observation period. CONCLUSIONS: The new triple agent regimen was effective against H. pylori. Resistance to clarithromycin may not be permanent and it might be one of the risk factors which affect the efficacy of a clarithromycin-based therapy.

Socioeconomic status and ulcer. A prospective study of contributory risk factors.

Peptic ulcer is associated with low socioeconomic status. In this study we used longitudinal population-based data to investigate factors other than Helicobacter pylori that might contribute to this association. Of 4597 Alameda County Study participants, 104 developed ulcers between 1965 and 1974. We examined the impact of baseline risk factors on the association between education and incident ulcer. Among women, high school dropouts had a higher risk of incident ulcer than those who attended college (age-adjusted odds ratio [OR], 3.3; 95% confidence interval [CI], 1.5, 7.3). Adjustment for smoking, alcohol, lack of sleep, skipping breakfast, chronic pain, and liver disease eliminated 21.7% of this excess risk, whereas adjustment for psychological characteristics and life stress eliminated 56.5% of the risk; adjusted for all risk factors, the OR was 1.9. Among men, the risk associated with low education was weaker (OR, 1.9; 95% CI, 0.9, 3.9). Health risk behaviors and poor health had a greater impact (55.5% drop in excess risk with adjustment) and psychosocial factors a lesser impact (33.3% drop) in men than in women. Adjustment for heavy on-the-job labor decreased the risk by 77.8%, whereas the fully adjusted OR was 1.0. We conclude that psychological stress, health risk behaviors, analgesic use, and hard physical labor may contribute to the increased risk of ulcer in low socioeconomic populations.

Detection methods of Helicobacter pylori: accuracy and costs.

A variety of methods exist for determining gastric colonization with Helicobacter pylori, which has been implicated in the development of peptic ulcer disease. The goal of this study was to evaluate four of the current methods available in a clinical surgical practice setting through a prospective evaluation of 40 consecutive patients undergoing upper diagnostic endoscopy. All patients underwent six antral gastric biopsies for use with the following detection methods: histologic demonstration of organisms (hematoxylin and eosin stain), direct detection of urease activity (Remel Selective Rapid Urea, Lenexa, KS), and culture of H. pylori. All patients also had measurement of serum immunoglobulin G for H. pylori by the enzyme-linked immunosorbent assay method (Corning Clinical Laboratories, St. Louis, MO). The infection status was established by a concordance of test results. The results show that H. pylori can be assessed equally well with histology, a rapid urease test, and serology, with all three tests having good sensitivity (92-100%) and specificity (85-96%). The culturing of the organism had poor sensitivity (42%). The benefits of the urease test are a much more rapid response time and a much lower cost as compared to histologic and serologic testing. In conclusion, the rapid urease test is the method of choice to detect H. pylori in those patients undergoing endoscopy in whom the identification of H. pylori will change their management.