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Histamine has an important role in the process of the gastric mucosa inflammation acting via histamine receptor H2 (encoded by the gene HRH2). Single nucleotide polymorphism of the enhancer element of HRH2 gene promoter rs2067474 (1018G>A)may be associated with changes of expression of the receptor. We attempted to clarify the association of this polymorphism with gastric cancer and/or atrophic gastritis in the Latvian (Caucasian) population. The study group consisted of 121 gastric cancer patients and 650 patients with no evidence of gastric neoplasia on upper gastrointestinal endoscopy. Genotyping for rs2067474 was performed with the TaqMan probe-based system using a commercially available probe for RT-PCR. The frequency of the A allele in the gastric cancer group was 0.41% and in the control group — 1.54% (p = 0.231). No significant differences were found comparing genotypes between gastric cancer versus control patients (OR = 0.236, CI95% = 0.030–1.896), patients with (n = 165) versus without (n = 485) gastric metaplastic lesions (OR = 0.854, CI95% = 0.288–2.540) and patients with (n = 297) and without (n = 353) gastric atrophic lesions (OR = 1.145, CI95% = 0.451–2.906). Our findings suggest that the HRH2 -1018G>A polymorphism (rs2067474) is neither associated with gastric cancer nor the grade of atrophic gastritis in the Latvian (Caucasian) population.

Background. The progression of Helicobacter pylori-associated gastritis towards atrophic gastritis is modulated by host-related and environmental factors. Studies that explore the possible involvement of host-related versus environmental factors in the development of gastritis phenotype induced by H. pylori are highly needed. Aims. Our study was aimed at investigating the phenotype of H. pylori-associated gastritis in two cohorts of monozygotic and dizygotic twins, using the OLGA/OLGIM gastritis staging system. Methods. Two cohorts of monozygotic (14 pairs) and dizygotic (15 pairs) dyspeptic twins prospectively underwent endoscopy with biopsy sampling based on Sydney protocol. H. pylori status and OLGA/OLGIM stages were assessed and compared. Results. The mean age of monozygotic and dizygotic twins was 40.4 and 38.6 years, respectively (p=0.623). The overall prevalence of H. pylori infection was 51.7%. Among the 14 monozygotic twin pairs, five pairs were H. pylori-positive, four were H. pylori-negative, and five were H. pylori-discordant. Among the 15 dizygotic twin pairs, five pairs were H. pylori-positive, five were H. pylori-negative, and five were H. pylori-discordant. Concordance for antrum atrophy in monozygotic twins was 78.6% (11/14 pairs) and in dizygotic twins 73.3% (11/15 pairs) (p=0.742). Concordance for corpus atrophy in monozygotic versus dizygotic twins was 92.9% (13/14 pairs) and 86.7% (13/15 pairs), respectively (p=0.584). Concordance for antrum intestinal metaplasia (IM) in monozygotic twins was 85.7% (12/14 pairs) and in dizygotic 73.3% (11/15 pairs) (p=0.411). Concordance for corpus IM in monozygotic twins was 85.7% (12/14 pairs) and in dizygotic 86.7% (13/15 pairs) (p=0.941). Among monozygotic and dizygotic subjects, the stage of gastritis was concordant in both H. pylori-positive and H. pylori-negative subjects. Conclusions. In conclusion, histological gastric mucosa alterations in monozygotic and dizygotic twins showed high rates of concordance. Furthermore, OLGA/OLGIM gastritis stages were not modulated by the zygosity of the twins.

Objective:To identify Helicobacter pylori infection in tonsillar tissue samples from patients undergoing tonsillectomy for chronic tonsillitis versus tonsillar hypertrophy, and to assess the possible relationships between H pylori and patients’ sociodemographic data and laryngopharyngeal reflux.Methods:In this prospective study, 97 patients who underwent tonsillectomy were divided into the following 2 groups: patients with chronic tonsillitis (n = 62) and patients with tonsillar hypertrophy (control group; n = 35). H pylori infection in the tonsillar biopsy samples was identified using histochemical and rapid urease tests.Results:The incidence of H pylori infection was significantly higher in the chronic tonsillitis group (56.5 per cent) compared to the control group (31.4 per cent). Similar findings were obtained for both subgroups of adults (68.6 vs 42.3 per cent) and children (40.7 vs 0.0 per cent). Significant relationships between a positive H pylori finding and laryngopharyngeal reflux related signs of vocal fold oedema, diffuse laryngeal oedema and hypertrophy of the posterior commissure were revealed.Conclusion:H pylori infection may be related to chronic tonsillitis and laryngopharyngeal reflux.

Aim Crohn’s disease (CD) is characterized by continuing inflammation and progressive gut damage. Despite many scoring indices of CD, there is a lack of more global assessment tools for the evaluation of the total disease impact on the gut. Methods Fift y-three adult patients with proven CD underwent magnetic resonance enterocolonography (MR-EC), colonoscopy, and clinical activity assessment, including CRP. Quality of life was assessed using IBDQ. MR-EC was used to evaluate the Magnetic Resonance Index of Activity (MaRIA- global (G)) and the Lemann Index (LI). The CD Endoscopic Index of Severity (CDEIS) was used to score the endoscopic activity of the disease. Results A signifi cant correlation between the LI and IBDQ was found (r=-0.812, P Conclusion A signifi cant negative correlation between the LI and quality of life, measured by IBDQ, was found in our study, suggesting that the LI could resemble more global features of the disease, besides inflammatory activity of the gut.

ObjectiveTo determine the prevalence of Helicobacter pylori infection in nasal biopsy specimens from patients with chronic rhinosinusitis with polyposis versus control patients, and to assess the correlations between H pylori infection identified in the nasal tissue and patients’ sociodemographic data and reflux-related symptoms and signs.MethodsNasal biopsy samples were taken from 75 adult patients who underwent nasal surgery for chronic rhinosinusitis with polyposis (clinical group, n = 45) and a deviated septum (control group, n = 30). H pylori infection was identified using histochemical and rapid urease tests.ResultsThe prevalence of intranasal H pylori infection was significantly higher in the clinical group (28.9 per cent) compared to the control group (3.3 per cent) (p = 0.005). A significant yet weak association was found between positive H pylori status and laryngopharyngeal reflux related hypertrophy of the posterior commissure of the larynx. No other correlations reached statistical significance.ConclusionH pylori infection is potentially related to chronic rhinosinusitis with polyposis. Further research is needed to clarify the role of H pylori as a risk factor for the development of sinonasal diseases and to examine its link with laryngopharyngeal reflux.

Background Secretion of pepsinogen I (PgI), pepsinogen II (PgII), fasting gastrin-17 (fG-17) and stimulated gastrin-17 (sG-17) changes after Helicobacter pylori eradication. Few data are available on the long-term dynamics of gastric biomarkers after H. pylori eradication.The aim of this study was to investigate the dynamics of gastric biomarkers in H. pylori-positive patients after eradication over a 3-year period and to compare the levels with initially H. pylori-negative patients. Materials and methods Blood samples for the detection of gastric biomarkers were obtained from dyspeptic patients coming for upper gastrointestinal endoscopy. In H. pylori-positive patients, after eradication therapy, three follow-up blood samples were drawn after 12, 24 and 36 months; in H. pylori-negative patients, two samples were taken - at 12 and after 30 months. Median values of biomarkers in follow-up samples were compared with the baseline sample. Results The final sample included 110 patients (median age 67 years, M/F ratio 27/83). In patients after H. pylori eradication (n=83) PgI, PgII, fG-17 and sG-17 had decreased significantly during a 36-month period, whereas the PgI/PgII ratio had increased significantly from 5.59 to 11.64. Conclusion In H. pylori-positive dyspeptic patients, after eradication therapy, a decrease in PgI, PgII, fG-17 and sG-17 was observed after 36 months whereas an increase in the PgI/II ratio suggested an improvement in gastric atrophy. The median levels of gastric biomarkers in patients after H. pylori eradication therapy may become similar to biomarker levels among initially H. pylori-negative individuals.

Background Circulating levels of pepsinogens have been used in high gastric cancer-risk Asian and European populations to triage endoscopic evaluation for more severe pathology. There are different analytic methods with uncertain correlations. We therefore compared diagnostic performance of three commonly used pepsinogen assays to detect histologically confirmed gastric atrophy. Methods We tested plasma samples from adult patients with (n=50) and without (n=755) moderate or severe gastric corpus atrophy, as determined histologically by consensus of three expert pathologists. A single laboratory measured pepsinogens I (PgI) and II (PgII) using commercially available assays: two ELISA assays produced by Biohit (Finland) and Vector Best (Russia), and a latex agglutination assay from Eiken (Japan). Quantitative correlations were assessed by Spearman statistics. Receiver operating characteristic (ROC) curves vs histological diagnosis were calculated using both the manufacturers' and optimized cutoffs. Results Pepsinogen levels were highly correlated among the assays (pairwise Rhos: PgI≥0.84, PgII≥0.87; all P-values

Atrophic gastritis remains a difficult histopathological diagnosis with low interobserver agreement. The aim of our study was to compare gastritis staging and interobserver agreement between general and expert gastrointestinal (GI) pathologists using Operative Link for Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia (OLGIM). We enrolled 835 patients undergoing upper endoscopy in the study. Two general and two expert gastrointestinal pathologists graded biopsy specimens according to the Sydney classification, and the stage of gastritis was assessed by OLGA and OLGIM system. Using OLGA, 280 (33.4 %) patients had gastritis (stage I–IV), whereas with OLGIM this was 167 (19.9 %). OLGA stage III– IV gastritis was observed in 25 patients, whereas by OLGIM stage III–IV was found in 23 patients. Interobserver agreement between expert GI pathologists for atrophy in the antrum, incisura angularis, and corpus was moderate (kappa = 0.53, 0.57 and 0.41, respectively, p

Introduction The Operative Link for Gastritis Assessment (OLGA) staging system has been proposed as a histopathological reporting system of gastric atrophy. Noninvasive methods for indirect evaluation of gastric mucosal atrophy by biomarkers are also being introduced. Objectives To analyze gastric mucosal atrophy by biomarkers, pepsinogen I (PgI), pepsinogen II (PgII), PgI/PgII ratio, fasting gastrin-17 (G-17), stimulated gastrin-17 (sG-17), in relation to OLGA gastritis stage. Patients and methods Gastric biopsies were taken from 269 prospective patients referred for upper endoscopy because of dyspeptic problems and evaluated by two expert pathologists (D.J. and P.S.). Atrophy was assessed according to the OLGA staging system. Pg I, PgII, Pg I/II, G-17, sG-17 were determined in a plasma sample. Results The mean levels of PgI and PgI/PgII decreased significantly from 90.8 μg/l and 7.6 in stage 0 gastritis to 64.3 μg/l and 4.3 in high-stage gastritis. The mean values of G-17 and sG-17 were significantly higher among patients with stage II gastritis compared with stage 0 and high-stage gastritis.The proportion of patients with normal mucosa and nonatrophic gastritis according to biomarkers decreased from 78% in stage 0 to 22% in high-stage (III-IV) gastritis. Among the latter no case with normal mucosa, according to biomarkers, was observed. Conclusions A significant inverse correlation between the mean levels of PgI, PgI/II ratio and the OLGA stage was observed. Percentage of dyspeptic patients with normal mucosa, by blood biomarkers, decreased with increasing OLGA gastritis stages. OLGA staging system provides a good frame for scientific analysis of gastric mucosal atrophy.

Background The efficacy of histological analysis of colon sections used for evaluation of inflammation severity can be improved by means of digital imaging giving quantitative estimates of main diagnostic features. The aim of this study was to reveal most valuable diagnostic features reflecting inflammation severity in colon and elaborate the evaluation method for computer-aided diagnostics. Methods Tissue specimens from 24 BALB/c mice and 15 patients were included in the study. Chronic and acute colon inflammation in mice was induced by oral administration of dextran sulphate sodium (DSS) solution, while mice in the control group did not get DSS. Human samples of inflamed colon tissue were obtained from patients with ulcerative colitis (n = 6). Non-inflamed colon tissue of control subjects (n = 9) was obtained from patients with irritable bowel syndrome or functional obstipation. Analysis of morphological changes in mice and human colon mucosa was performed using 4-μm haematoxylin-eosin (HE) sections. The features reflecting morphological changes in the images of colon mucosa were calculated by convolution of Gabor filter bank and array of pixel values. All features were generalized by calculating mean, histogram skewness and entropy of every image response. Principal component analysis was used to construct optimal representation of morphological changes. Results First principal component (PC1) was representing the major part of features variation (97 % in mice and 71 % in human specimens) and was selected as a measure of inflammation severity. Validation of new measure was performed by means of custom-made software realizing double blind comparison of differences in PC1 with expert’s opinion about inflammation severity presented in two compared pictures. Overall accuracy of 80 % for mice and 67 % for human was reached. Conclusion Principal component analysis of spatial frequency features of histological images may provide continuous scale estimation of inflammation severity of colon tissue.

Helicobacter pylori is the most important cause of gastritis, peptic ulcers and the development of gastric cancer. The chronic active inflammation is dominated by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins (IL-8, IL-10 and IFN-c) are involved in the inflammatory process in the gastric mucosa. The aim of this study was to investigate the gastric inflammation in patients with functional dyspepsia. Fifty-three consecutive patients were included and antral biopsies were obtained for histology, culture and immunohistochemistry. The sections were examined for the interleukins IL-4, IL-6, IL-8, IL-10 and IFN-c as well as for the cell markers CD4, CD8, CD14, Cd19, CD25 and CD30. Only CD4 and CD19 were significantly increased in patients with increased gastric inflammation and increased density of H. pylori. However, several of the examined markers (IFN-c, IL-8, IL-10 and CD14) showed a non-significant trend to be increased in patients with extensive gastric inflammation and high density of H. pylori. Therefore, an arbitrary index (IM11) for all the 11 immunological markers was made as an average value for each of the four morphological groups. For the four morphologically different groups of patients the values were 0.49, 0.77, 0.86 and 1.25, respectively. Significant increases in the index from none to moderate antral inflammation as well as the density of H. pylori were found (p < 0.001). By using an index of inflammatory markers trends can be summarized and thereby significant which may be of importance when gastric inflammation is investigated in children and patients with functional dyspepsia. 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

OBJECTIVES It is important to stratify patients according to the magnitude of risk for gastric cancer development; the OLGA (Operative Link for Gastritis Assessment) and OLGIM (Operative Link on Gastric Intestinal Metaplasia) staging systems of lesions in the stomach mucosa have been proposed for this purpose. There are some discrepancies in the current guidelines regarding the value of incisura angularis biopsies. The aim of our study was to assess the value of incisura angularis biopsy in staging gastritis according to the OLGA and OLGIM systems by examining the atrophic, metaplastic and inflammatory changes in the antrum, incisura angularis and corpus. PATIENTS AND METHODS We enrolled 835 patients undergoing upper endoscopy. Three expert gastrointestinal pathologists graded biopsy specimens according to the Sydney classification and the stage of gastritis was assessed by the OLGA and OLGIM systems. RESULTS The results demonstrated that severe atrophic, metaplastic and chronic inflammatory changes were more frequently observed in the incisura angularis mucosa than in the antrum or corpus mucosae (P

Background Either atrophy or intestinal metaplasia of the gastric mucosa are considered premalignant lesions. The new operative link for gastritis assessment staging system is based on the detection of atrophy, and the operative link for assessment of intestinal metaplasia staging system is based on the detection of intestinal metaplasia. Good interobserver agreement is necessary for identification of any premalignant condition. Aims The aim of this study was to compare the agreement between findings of gastric atrophy and intestinal metaplasia by expert and general pathologists and to analyze the possible reasons behind any possible disagreement. Methods Patients with dyspeptic symptoms, aged 55 years and above, without previous Helicobacter pylori eradication were enrolled and analyzed according to the updated Sydney Classification by two expert pathologists and an experienced general pathologist; the results were compared with the consensus driven by the two experts. Results Gastric biopsy specimens from 121 patients (91 women) were included in the analysis; the mean age of the patients was 67.4 years. H. pylori infection was present in 61.2% of patients. The level of agreement between the general pathologist and the two experts (κ-value) was 0.12, 0.46, and 0.87, respectively, for detecting atrophy in the corpus; 0.77, 0.77, and 0.65, respectively, for detecting intestinal metaplasia in the corpus; 0.06, 0.51, and 0.54, respectively, for detecting atrophy in the antrum; and 0.69, 0.85, and 0.79, respectively, for detecting metaplasia in the antrum. Conclusion The agreement was substantially higher for intestinal metaplasia than for atrophy. This could result in discrepancies when the operative link for gastritis assessment and operative link for assessment of intestinal metaplasia staging systems are applied and can be caused by differences in the criteria used to define atrophy.

Decreased plasma gastrin-17 (G-17), particularly after protein stimulation, is indicative of atrophy in the antral stomach mucosa. Available data on the value of this biomarker is inconclusive. Our study was aimed to evaluate the performance of the G-17 test in Caucasian and Asian patients for antral atrophy evaluation either in fasting state or after protein stimulation.241 dyspeptic patients aged 55 and above from Latvia (125), Lithuania (76) and Taiwan (40) were enrolled. G-17 levels were detected in plasma samples obtained either during fasting or after a protein-rich test meal. Levels1 pmol/L at fast and5 pmol/L after stimulation were considered indicative of atrophy.The sensitivity of the test was 15.8%, its specificity 88.7%, and the overall accuracy 83% in the fasting state, and 36.8, 86.5, and 82.6%, respectively, after stimulation. In the Caucasian subgroup, the corresponding figures were 15.4, 91.5, and 86.6% in the fasting state and 30.8, 92.6, 88.6% after stimulation; but for the Asian subgroup the corresponding figures were 16.7, 73.5, and 65% (fasting) and 50, 52.9, and 52.5% (stimulated).The performance of G-17 was better after protein stimulation. G-17 was highly specific in the Caucasian, but not in the Asian subgroups. Still the low test sensitivity either at fast or following protein stimulation does not allow us to recommend it for wide screening purpose to diagnose antral atrophy.

Objective Contradictory results have been reported about the role of interleukin-1B (IL1B) and IL1 receptor antagonist (IL1RN) alleles in gastric carcinogenesis. Here, IL1B and IL1RN polymorphisms were analyzed as genotypes and haplotypes in relation to the presence of atrophic gastritis (AG) and intestinal metaplasia in the stomach. Methods Two hundred and seventy-eight patients (212 Caucasians and 66 Asians) aged 50 years and above, referred for upper endoscopy because of dyspeptic symptoms, were included in the study. Gastric biopsies were histologically assessed according to the updated Sydney classification. Genomic DNA was typed for polymorphisms at position -3737, -1464, -511, -31 for the IL1B gene and the allele 2 of IL1RN using restriction fragment length polymorphism of amplified PCR fragments and intron-spanning PCR analysis, respectively. Results IL1B-1464-C/C genotype was associated with higher presence of AG in antrum of the stomach in Caucasians [odds ratio: 4.8 (95% confidence interval = 1.7-14.3); P=0.028]. IL1B-1464-G/C genotype was associated with lower incidence of AG in corpus of the stomach in Asians [odds ratio: 0.7 (95% confidence interval =0.5-0.8); P=0.02]. IL1RN * 2 allele was not linked with AG or intestinal metaplasia in all parts of the stomach both among Asians and Caucasians. Overall, data show that none of the major four IL1B polymorphisms (IL1B-3737C>T, -1464G>C, -511C>T, -31T>C) and the IL1RN * 2 is individually, or in its haplotype configuration, linked to the presence of premalignant lesions in Caucasians. Conclusion The determination of these IL1-related loci does not have any predictive value for stratification of subgroups with respect to gastric cancer risk.

Atrophy of the stomach mucosa is considered to be premalignant lesion for gastric cancer development; easy identification of this condition from a blood-sample would allow identifying the group of individuals at increased risk for cancer development. The objective of the current study was to validate a biomarker method (pepsinogen I/II ratio and gastrin-17) for indirect detection of atrophy of the stomach mucosa versus standard histopathology in Caucasian and Asian populations. Altogether, 241 patients aged 55 and above referred for upper endoscopy due to dyspeptic symptoms (125 from Latvia, 76 from Lithuania, and 40 from Taiwan) were enrolled. Pepsinogen I, pepsinogen II, gastrin-17 (the latter after stimulation with protein-rich meal) and IgG/IgA antibodies to Helicobacter pylori infection were determined by ELISA method; standard histopathology according to the updated Sydney classification read by two independent expert pathologists was used for the comparison. Pepsinogen I/II ratio below 3 was well related to atrophy (moderate to severe) in the corpus part of the stomach (P

Objective. We present our experience in diagnosing, gender assignment, and surgical management of sexual ambiguity in 46,XY mixed gonadal dysgenesis. Material and methods. A retrospective study of five cases treated from 2003 to 2006 was performed. Clinical picture, operative findings, testosterone levels, and immunohistochemistry of gonads for the expression of FOXL2, SOX9, AMH, AMHr, C-kit, and PLAP were analyzed. Results. All patients had ambiguous genitalia, urogenital sinus, uterus, testicle on one side, and a streak gonad on the other. Four patients were reared as male and one as female. Stimulation by human chorionic gonadotropin showed good penile size and testosterone response. All patients underwent laparoscopic gonadal biopsy and/or gonadectomy. Histological studies showed the presence of sparse primordial follicles surrounded by embryonic sex cords in the streak portion of gonads. Germ cells were C-kit positive in all and PLAP positive in four patients. FOXL2 expression was detected in four streak gonads and in none of testes. AMH expression was found only in testes. SOX9 expression was found in both investigated testes and in three out of four streak gonads investigated. Conclusions. 46,XY mixed gonadal dysgenesis should be differentiated from ovotesticular and other types of 46,XY disorders of sexual differentiation by the typical gonadal histology and internal genital structure. High testosterone level after stimulation and good response to testosterone treatment in 46,XY mixed gonadal dysgenesis could orient toward male sex assignment. There are different patterns of gene expression in testicular and streak gonads with a switch to FOXL2 positivity in streak gonads. Early gonadal and genital surgery is recommended.

Background Atrophy of the stomach mucosa is considered to be premalignant lesion for gastric cancer development; easy identification of this condition from a blood-sample would allow identifying the group of individuals at increased risk for cancer development.