GastroPanel® Biomarker Assay: The Most Comprehensive Test for Helicobacter pylori Infection and Its Clinical Sequelae. A Critical Review.

BACKGROUND/AIM: Several clinical conditions seriously hamper the diagnostic accuracy of the commonly used tests for Helicobacter pylori (Hp), 13C-urea breath test (UBT) and stool antigen test (SAT). The present communication is a critical review of the potential limitations of UBT and SAT, and describes the approach on how these can be avoided. Drawbacks of the Hp tests: False-negative results are most often due to low bacterial load in the stomach due to: i) use of proton pump inhibitor medication; ii) use of antibiotics; iii) presence of atrophic gastritis and hypoacid stomach; iv); bleeding peptic ulcer; v) gastric cancer (GC) and vi) mucosal-associated lymphatic tissue lymphoma. The UBT also gives false-positive results when urease-producing bacterial species, other than Hp colonize an acid-free stomach. Importantly, neither UBT nor SAT are capable of diagnosing atrophic gastritis, thus missing the patients at highest risk for GC. GastroPanel® (Biohit Oyj, Finland) circumvents these shortcomings with a serological test consisting of a panel of stomach-specific biomarkers: pepsinogen I, pepsinogen II, gastrin-17 and Hp antibodies. GastroPanel® is a tool for non-invasive examination of i) dyspeptic patients for exclusion or diagnosis of Hp or atrophic gastritis, also disclosing the status of gastric acid output; ii) for screening of asymptomatic individuals at risk of GC; and iii) for comprehensive diagnosis of Hp infection. GastroSoft® application integrates the biomarker profile with the patient's medical information, accurately classifying the biomarker profiles into eight diagnostic categories. CONCLUSION: Given that Hp is the single most important risk factor of GC, the non-invasive diagnosis and screening of Hp should be based on more accurate and more comprehensive testing than UBT or SAT alone. The GastroPanel® is such test, being completely devoid of the known serious shortcomings of UBT and SAT.

Challenges in evaluation of screening for gastric cancer among men based on nonrandomized design.

BACKGROUND: Objective was to quantify biases in screening for gastric cancer when comparing attenders to nonattenders using serum pepsinogen I (SPGI) level as primary test. METHODS: In mid 1990s, all men aged 51-65 years from two Finnish cities were invited to SPGI screening. Mortality and premature mortality in attenders were compared to nonattenders. Efficacy of screening was studied by 15 years' follow-up of standardized mortality ratio (SMR) and potential years of life lost (PYLL) due to gastric cancer. Bias due to selective attendance was quantified using corrective coefficients based on total cancer incidence and mortality, and gastric cancer-specific incidence and mortality for total population and nonattenders. RESULTS: In 1994-1996, men aged 51-65 years (16,872) were invited to SPGI assay and 12,175 men (72%) attended. SPGI was 25 microg/l or less in 610 (5%) men, indicating severe atrophic gastritis (AG). Post-screening gastroscopy was performed to 435 men with low SPGI. Of these, 168 men were referred for treatment due to abnormal focal lesions. Attributable proportions in reductions of SMR and PYLL from gastric cancer due to screening were 59% and 67%. After correcting for selective participation, attributable proportions were reduced to 23% and 39%. CONCLUSIONS: Biomarker screening by low SPGI among middle-aged men followed by upper gastrointestinal endoscopy decreased long-term and premature mortality due to gastric cancer. However, in spite of methodological corrections done, the results do not justify any firm conclusions or recommend general screening programs. Randomized trials are warranted for this purpose.

Risk of gastric cancer in Helicobacter pylori infection in a 15-year follow-up.

OBJECTIVE: We investigated the risk of gastric cancer among men with Helicobacter pylori (H. pylori) infection or atrophic gastritis (AG) in a 15-year follow-up. MATERIALS AND METHODS: Study population consists of 12,016 men aged 50-65 years at the beginning of the follow-up in 1994-1996. Serum levels of pepsinogen I (SPGI) and antibodies (IgG) to H. pylori (HpAb) were assayed from serums collected in 1994-1996. Incidence of gastric cancer in the study population was assessed in follow-up from 1994 to 2011 by data from the nationwide cancer registry. Based on SPGI and HpAb values, standardized incidence ratios (SIRs) of gastric cancer were calculated in three subgroups, that is, in those with a healthy stomach, those with H. pylori infection but without AG and those with AG. Risk ratios (RR) of gastric cancer were calculated using SIR of subgroups. RESULTS: During 15 years, seven gastric cancers appeared per 79,928 person years among men with healthy stomachs, 50 cancers per 92,533 person years in men with H. pylori infection but without AG, and 8 per 8658 person years in men with AG. Risk ratio (RR) of stomach cancer in men with H. pylori infection was 5.8 (95%CI: 2.7-15.3) compared to men with healthy stomachs, and 9.1 (95%CI: 2.9-30.0) in men with AG. There were no differences in cancer risk between cardia and distal stomach. CONCLUSIONS: Risk of gastric cancer is low in men with healthy stomachs. It is significantly increased in those with H. pylori infection and more in those with AG.

Prevalence of undiagnosed advanced atrophic corpus gastritis in Finland: an observational study among 4,256 volunteers without specific complaints.

OBJECTIVE: The objective of this observational study was to estimate the prevalence of advanced atrophic corpus gastritis (ACG) among Finnish adult volunteers without specific complaints using a biomarker blood test. The objective also was to assess the feasibility and acceptance of the biomarker test among the volunteers. MATERIALS AND METHODS: GastroView biomarker test (Biohit Oyj, Helsinki, Finland) was performed on mostly fingerprick blood samples from 4,256 volunteers (average age 56 years, range 18-92 years), independent of symptoms. GastroView biomarker test was offered to citizens at public events during 2007-2009. The test consisted of the measurement of pepsinogen I and II levels (and ratio) and H. pylori IgG antibody level in plasma by ELISA. RESULTS: Altogether 3.5% (150 individuals) of all 4,256 volunteers had ACG. In the age group of 70 or over, the prevalence of ACG increased to 8% (62 individuals). Altogether 19% (819 individuals) of all volunteers and 37% (56 individuals) of those with ACG had an ongoing H. pylori infection. In volunteers with ACG, the diagnosis was new in 95% (142 individuals), 5% (7 individuals) had received vitamin B12 supplementation and 13% (20 individuals) had received PPI medication according to a self-administered questionnaire; and 26% (39 individuals) reported gastrointestinal reflux like symptoms. CONCLUSIONS: This study shows that advanced ACG is a common disease among Finnish adults, and remains to be undiagnosed in most under the current healthcare practice. The biomarker test shows high feasibility and acceptance among the general public, and is simple to perform even in "field" conditions.

Hypochlorhydric stomach: a risk condition for calcium malabsorption and osteoporosis?

Malabsorption of dietary calcium is a cause of osteoporosis. Dissolution of calcium salts (e.g. calcium carbonate) in the stomach is one step in the proper active and passive absorption of calcium as a calcium ion (Ca(2+)) in the proximal small intestine. Stomach acid markedly increases dissolution and ionization of poorly soluble calcium salts. If acid is not properly secreted, calcium salts are minimally dissolved (ionized) and, subsequently, may not be properly and effectively absorbed. Atrophic gastritis, gastric surgery, and high-dose, long-term use of antisecretory drugs markedly reduce acid secretion and may, therefore, be risk conditions for malabsorption of dietary and supplementary calcium, and may thereby increase the risk of osteoporosis in the long term.

Low circulating levels of gastrin-17 in patients with Barrett's esophagus.

AIM: To examine whether the fasting levels of serum gastrin-17 (G-17) are lower in Barrett's esophagus (BE) patients than in non-Barrett controls. METHODS: Nineteen patients with BE (presenting with a tubular segment > or =2 cm long in lower esophagus and intestinal metaplasia of incomplete type ("pecialized columnar epithelium") in endoscopic biopsies from the tubular segment below the squamocolumnar junction were collected prospectively from outpatients referred to diagnostic gastroscopy. The controls comprised 199 prospectively collected dyspeptic outpatients without BE or any endoscopically visible lesions in the upper GI tract. Fasting levels of serum G-17 (G-17fast) were assayed with an EIA test using a mAb highly specific to amidated G-17. None of the patients and controls received therapy with PPIs or other antisecretory agents. RESULTS: The mean and median levels of G-17fast in serum were significantly lower (P = 0.001) in BE patients than in controls. The positive likelihood ratios (LR+) of low G-17fast to predict BE in the whole study population at G-17fast levels <0.5, <1, or <1.5 pmol/L were 3.5, 3.0, and 2.8, respectively. Among patients and controls with healthy stomach mucosa, the LR+ were 5.6, 3.8, and 2.6, respectively. In the whole study population, serum G-17 was below 2 pmol/L in 15 of 19 BE patients (79%). The corresponding prevalence was 66 of 199 (33%) in controls (P<0.001). The G-17fast was 5 pmol/L or more in only one of the 19 BE patients (5%). In controls, 76 of the 199 patients (38%) had such high serum G-17fast levels (P<0.01). CONCLUSION: Serum levels of G-17fast tend to be lower in native patients with BE than in healthy controls.

Effect of chronic ethanol ingestion and gender on heart left ventricular p53 gene expression.

BACKGROUND: Although the beneficial effects of mild to moderate ethanol consumption have been implied with respect to heart, alcohol abuse has proven to be a major cause of nonischemic cardiomyopathy in Western society. However, the biochemical and molecular mechanisms, which mediate the pathologic cardiac effects of ethanol, remain largely unknown. The aim of the present study was to explore the effects of chronic ethanol exposure on cardiac apoptosis and expression of some of the genes associated with cardiac remodeling in vivo. METHODS: Alcohol-avoiding Alko Non Alcohol rats of both sexes were used. The ethanol-exposed rats (females, n=6; males, n=8) were given 12% (v/v) ethanol as the only available fluid from age of three to 24 months of age. The control rats (females, n=7; males, n=5) had only water available. At the end of the experiment, free walls of left ventricles of hearts were immediately frozen. Cytosolic DNA fragmentation, reflecting apoptosis, was measured using a commercial quantitative sandwich enzyme-linked immunosorbent assay kit, and mRNA levels were analyzed using a quantitative reverse transcriptase-polymerase chain reaction method. RESULTS: Ethanol treatment for two years increased cardiac left ventricular p53 mRNA levels significantly (p=0.014) compared with control rats. The gene expression was also dependent on the gender (p=0.001), so that male rats had higher left ventricular p53 mRNA levels than female rats. However, no significant differences in levels of DNA fragmentation were detected. CONCLUSIONS: Chronic ethanol exposure in vivo induces rat cardiac left ventricular p53 gene expression. Expression of p53 is also gender-dependent, males having higher p53 mRNA levels than females. This preliminary finding suggests a role for the p53 gene in ethanol-induced cardiac remodeling. The results might also have some relevance for the known gender-dependent differences in propensity to cardiovascular disease.

Changes in the histology and function of gastric mucosa and in Helicobacter pylori colonization during a long-term follow-up period after vagotomy in duodenal ulcer patients.

BACKGROUND/AIMS: To investigate changes in the histology and the Helicobacter pylori (H. pylori) prevalence and density of the gastric mucosa, as well as in fasting serum gastrin and serum pepsinogen I, depending on completeness of vagotomy, and in cases of recurrent ulcer, during 14 years after operation in duodenal ulcer patients. METHODOLOGY: 122 vagotomized duodenal ulcer patients were studied twice on average 9 and 14 years after operation. The presence of recurrent ulcer and completeness of vagotomy were assessed simultaneously endoscopically and by endoscopic Congo red test. The histology of the gastric antrum and corpus mucosa was assessed in accordance with the Sydney system. The amount of H. pylori in the specimens was detected by microscopic counting; gastrin and pepsinogen I in serum were determined radioimmunologically. RESULTS: During the 14-year follow-up period, complete vagotomy patients were characterized by a smaller amount of active antrum gastritis and a larger amount of active chronic corpus gastritis involving corpus atrophy in 46% of cases 14 years after operation. Recurrent ulcer patients were characterized by a significantly higher prevalence of high-grade H. pylori colonization and active mucosal inflammation in the antrum as well as by a lower level of active mucosal inflammation and atrophy in the corpus and a higher serum pepsinogen I level compared with complete vagotomy cases. The data of incomplete vagotomy patients without recurrent ulcer became more similar to those recorded for recurrent ulcer patients. CONCLUSIONS: In duodenal ulcer patients, changes in the histology of the gastric antrum and corpus mucosa as well as in H. pylori prevalence and density and in serum pepsinogen I levels are different depending on completeness of vagotomy during 14 years after operation.

Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis.

Background. Only a few reported studies focus on the natural history and course of advanced and severe chronic atrophic gastritis. Methods. In this study we followed 47 men (mean age 62 years) with advanced (moderate or severe) Helicobacter pylori-positive atrophic corpus gastritis. Duration of endoscopic follow-up was 6 years and follow-up based on serum levels of pepsinogen I and antibodies to H. pylori covered a period of 10 years. None of the patients was treated for H. pylori infection prior to end of follow-up. Results. The median H. pylori antibody titre declined (IgG from 4000 to 1300; IgA from 200 to 50) in the study population, and 11 men (23%) converted to seronegative (p=0.0005, Fisher's exact test). There was a small but significant (p=0.0004, Page's test) declining trend in mean atrophy score of the corpus during follow-up (from 2.5 to 2.2). However, no significant changes were observed in grade of atrophy or intestinal metaplasia of the antral mucosa or in grade of intestinal metaplasia in the corpus. The mean SPGI level remained at the initial low level during the entire follow-up. Conclusions. H. pylori antibodies disappear spontaneously within 10 years in almost one fourth of patients with advanced atrophic corpus gastritis. The disappearance of H. pylori antibodies is accompanied by no or more than a mild improvement of the gastric mucosa.

Diagnosis of atrophic gastritis from a serum sample.

On the basis of the levels of serum pepsinogen I (S-PGI) and gastrin-17 (S-G-17) as well as Helicobacter pylori - antibodies assayed from a blood sample it is possible to establish with high sensitivity and specificity whether the patient has gastritis, whether the gastritis is atrophic or not and in which part of the stomach the atrophic changes are located. The test enables the identification of patients whose risk of gastric cancer, of the consequences of vitamin B12 deficiency (e.g. elevated levels of homocysteine) or of peptic ulcer is considerably increased and who can then undergo gastroscopy. It also facilitates the diagnosis of non-atrophic Helicobacter gastritis enabling treatment before endoscopy.

Combined calcium carbimide and ethanol treatment induces high blood acetaldehyde levels, myocardial apoptosis and altered expression of apoptosis-regulating genes in rat.

The effects of ethanol and ethanol-derived acetaldehyde on rat myocardial apoptosis and expression of genes involved in the regulation of apoptosis and cell cycle arrest were studied. Combined ethanol and calcium carbimide treatment for 2, 5 or 8 days (E + CC) markedly increased blood acetaldehyde levels. Cytosolic DNA fragmentation was quantified in the 5-day treatment group. Increased amount of DNA-fragmentation, reflecting increased apoptosis, was evident in the E + CC group (23% increase compared to controls). mRNA levels of genes regulating apoptosis were measured by using quantitative PCR in the 2- and 8-day treatment groups. In the 2-day treatment group, p21 gene expression was increased by 25% and bax/bcl-2 mRNA ratio by 57% in E + CC, compared to the control, group. In the 8-day treatment group, p21 mRNA level was 24% lower, p53 mRNA level was 15% higher (P < 0.005), and bcl-2 mRNA level 36% higher in E + CC-treated, compared to the control, group. Interestingly, both ethanol and calcium carbimide treatments alone increased bax mRNA levels, as compared to the control group at 2 and 8 days. These results indicate that acetaldehyde might regulate the expression of apoptosis-linked genes and that apoptosis of myocardial cells may be involved in the development of alcoholic heart disease.