Collagenous Gastritis in Children: Incidence, Disease Course, and Associations With Autoimmunity and Inflammatory Markers.

INTRODUCTION: Collagenous gastritis (CG), a rare disorder of unknown etiology, has been postulated to have immune-mediated mechanisms. We investigated (i) the incidence and prevalence of CG in a pediatric population; (ii) the clinical, endoscopic, and histologic characteristics of childhood-onset CG; and (iii) the evidence for autoimmunity and/or inflammatory activity in these patients. METHODS: Clinical, endoscopic, and histologic data were reviewed longitudinally in a population-based Swedish cohort of 15 patients with childhood-onset CG diagnosed in the period 2008-2019. A set of 11 autoantibodies, 4 blood inflammatory biomarkers, and the human leukocyte antigen DQ2/DQ8 genotype was analyzed cross-sectionally. RESULTS: The incidence rate of childhood-onset CG was 0.25/100,000 person-years, with an incidence rate ratio of girls to boys of 4.2 (95% confidence interval, 1.2-15). The prevalence of CG was 2.1/100,000 in children aged younger than 18 years. The endoscopic and histologic findings remained pathologic in all the examined patients during a median follow-up of 4.4 years. Many patients had heredity for autoimmune disorders (47%) and/or tested positive for autoantibodies (40%) or human leukocyte antigen DQ2/DQ8 (53%). No associated autoimmune comorbidities were observed. The serum levels of calprotectin and amyloid A were increased in 10/15 (67%) and 5/15 (33%) of the patients, respectively, whereas plasma C-reactive protein levels were normal in all, but 1 patient. DISCUSSION: The results indicate that childhood-onset CG is rare and has a chronic disease course. Although signs of autoimmune predisposition are frequent, early development of autoimmune comorbidities seems seldom. Serum calprotectin and amyloid A represent novel candidate biomarkers of inflammatory activity in CG (see Visual Abstract, Supplementary Digital Content 4, http://links.lww.com/CTG/A349).

Chromogranin Serves as Novel Biomarker of Endocrine and Gastric Autoimmunity.

CONTEXT: The glycoprotein chromogranin A (CgA) is expressed by endocrine and neuroendocrine cells. High levels of serum CgA serve as markers of neuroendocrine tumors (NET), but its role in autoimmunity has not been assessed. OBJECTIVE: To investigate CgA utility as a marker of endocrine autoimmunity. METHODS: CgA serum levels were evaluated in 807 consecutive unselected participants (cross-sectional study) with the time-resolved amplified cryptate emission technology. RESULTS: Serum CgA concentrations were increased in 66%, 39%, 38%, and 24% of patients with NET, type 1 diabetes (T1D), autoimmune gastritis (AG) and autoimmune polyendocrinopathy (AP), respectively. Compared with healthy participant controls (C), the odds of positive CgA measurement were up to 28 times higher in the disease groups. In detail, the odds ratios (ORs) for positive CgA levels were 27.98, 15.22, 7.32 (all P < 0.0001) and 3.89 (P = 0.0073) in patients with NET, T1D, AG, and AP, respectively. In AG, CgA and serum gastrin correlated positively (r = 0.55; P < 0.0001). The area under the receiver operating characteristic curve to predict AG was higher for parietal cell antibody (PCA) positivity than for CgA (0.84 vs 0.67; P < 0.0001). However, in combination with PCA and intrinsic factor autoantibodies, CgA independently improved prediction of AG (OR 6.5; P = 0.031). An impact of age on CgA positivity and on CgA value was detected (P < 0.0001) while current smoking significantly increased CgA serum levels by 25% (P = 0.0080). CONCLUSION: CgA qualifies as a novel biomarker for T1D, AP, and AG.

Serum pepsinogens as a gastric cancer and gastritis biomarker in South and Southeast Asian populations.

Serum pepsinogens have been widely acknowledged as gastric mucosal biomarkers; however, a multicountry report on the benefits of pepsinogens as biomarkers has not yet been published. We analyzed 1,206 sera and gastric mucosal samples collected from Bangladesh, Bhutan, Indonesia, Myanmar, Nepal and Thailand then assessed the association between gastric mucosal changes and Helicobacter pylori infection. The new cutoff values for serum pepsinogen values were evaluated using a receiver operating characteristic analysis. The participants with H. pylori infection had significantly lower pepsinogen I and higher pepsinogen II values, but a lower pepsinogen I/II ratio than participants without the infection (all P < .001). The pepsinogen I and pepsinogen I/II values were significantly higher and lower, respectively, in individuals with atrophic gastritis than in those without (both P < .001). Among uninfected individuals, only the pepsinogen I/II ratio was significantly lower in atrophic individuals. Pepsinogen I/II ratio also were significantly different between disease among H. pylori-positive and H. pylori-negative individuals, suggesting the pepsinogen I/II ratio is a robust biomarker for determining both chronic and atrophic gastritis. The cutoffs for detecting chronic and atrophic gastritis for the pepsinogen I/II ratio were 4.65 and 4.95, respectively. In conclusion, pepsinogen levels are useful biomarker for both chronic gastritis and atrophic gastritis, but they should be used with caution. Population-based validation is necessary to determine the best cutoff values. Among all pepsinogen values, the pepsinogen I/II ratio was the most reliable gastric mucosal-change biomarker.

LncRNAs adjacent to pepsinogen C in gastric diseases and diagnostic efficiencies of joint detection in gastric diseases.

Aims: We aimed to explore diagnostic efficiencies of long noncoding RNAs (lncRNAs) adjacent to PGC combining with sPGC and anti-Helicobacter pylori IgG in identifying GC (gastric cancer) and precancerous disease. Patients & methods: A total of 265 patients with different gastric diseases were collected. ELISA was to detect sPGC and anti-H. pylori IgG. LncRNAs was determined by qRT-PCR. Results: The area under receiver operating characteristic curve of lncRNAs in discriminating GC+AG (atrophic gastritis) and superficial gastritis (SG) were 79.0, 68.1 and 75.9%. The diagnostic performance of lncRNAs with sPGC had increasing trends in distinguishing GC from non-GC, SG from GC+AG comparing with lncRNAs, with no statistic difference. Diagnosis efficacies of lncRNAs with anti-H. pylori IgG improved dramatically. Conclusions: Serum lncRNAs could distinguish GC, AG and SG. Diagnosis efficiencies of lncRNAs with sPGC and anti-H. pylori-IgG could be improved.

Gastric cancer in autoimmune gastritis: A case-control study from the German centers of the staR project on gastric cancer research.

OBJECTIVES: Patients with autoimmune gastritis (AIG) are reported to have an increased risk of developing gastric cancer (GC). In this study, we assess the characteristics and outcomes of GC patients with AIG in a multicenter case-control study. METHODS: Between April 2013 and May 2017, patients with GC, including cancers of the esophagogastric junction (EGJ) Siewert type II and III, were recruited. Patients with histological characteristics of AIG were identified and matched in a 1:2 fashion for age and gender to GC patients with no AIG. Presenting symptoms were documented using a self-administered questionnaire. RESULTS: Histological assessment of gastric mucosa was available for 572/759 GC patients. Overall, 28 (4.9%) of GC patients had AIG (67 ± 9 years, female-to-male ratio 1.3:1). In patients with AIG, GC was more likely to be localized in the proximal (i.e. EGJ, fundus, corpus) stomach (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.0-7.1). In GC patients with AIG, pernicious anemia was the leading clinical sign (OR 22.0, 95% CI 2.6-187.2), and the most common indication for esophagogastroduodenoscopy (OR 29.0, 95% CI 7.2-116.4). GC patients with AIG were more likely to present without distant metastases (OR 6.2, 95% CI 1.3-28.8) and to be treated with curative intention (OR 3.0, 95% CI 1.0-9.0). The five-year survival rates with 95% CI in GC patients with and with no AIG were 84.7% (83.8-85.6) and 53.5% (50.9-56.1), respectively (OR 0.25, 95% CI 0.08-0.75, p = 0.001). CONCLUSIONS: Pernicious anemia leads to earlier diagnosis of GC in AIG patients and contributes significantly to a better clinical outcome.

Eosinophil counts in colonic tissue eosinophilia: Investigating specificity and sensitivity of cutoff points and comparing two counting methods.

BACKGROUND/AIMS: The aim of this study was to investigate the specificity and sensitivity of eosinophil cutoff points defining the colonic tissue eosinophilia (TE) and compare the yield of reporting the highest count versus the mean of five high-power fields (HPFs). MATERIALS AND METHODS: One hundred and seventy-one cases of colonic TE, including 22 primary eosinophilic colitis (PEC) cases, were compared to one hundred and twenty-one normal controls in the University of Jordan. The highest eosinophil count (EC) and the mean of five HPFs were recorded. The receiver operating characteristic curve (ROC) analysis was used to find the cutoff point with the best sensitivity and specificity. RESULTS: There was no significant advantage of counting five fields over counting the most densely populated HPF. Using 30 eosinophils per HPF achieved 80% sensitivity and 65% specificity. This point is close to the mean in normal controls plus one standard deviation (SD) (29 per HPF). However, there was overlap between normal counts and TE, using 30 as a cutoff point resulted in 35% false-positive rate. There was no reliable cutoff point to differentiate PEC from secondary TE. CONCLUSION: We recommend reporting the highest EC in colonic biopsies and using 30 as a cutoff point, bearing in mind the overlap with normal and correlating with the clinical team to not treat asymptomatic patients. Clinicopathological correlation is essential to separate PEC from secondary TE.

Anti-gastric parietal cell antibodies for autoimmune gastritis screening in juvenile autoimmune thyroid disease.

OBJECTIVE: Patients with autoimmune thyroid disease (ATD) have a higher prevalence of autoimmune gastritis (AIG) compared with the general population. The association between ATD and AIG is poorly characterized in the pediatric age. We reviewed the prevalence of anti-gastric parietal cell antibodies (PCA) in young patients with ATD to evaluate its usefulness as a marker for AIG screening. METHODS: We evaluated 220 children and adolescents (11.28 ± 6.37 years) with ATD (186 with autoimmune thyroiditis (AT) and 34 with Graves' disease (GD). At ATD diagnosis and annually thereafter, blood counts and PCA levels were measured. In patients positive for PCA, plasma gastrin, chromogranin A, vitamin B12, iron and ferritin levels and H. pylori antigen were measured. PCA-positive patients > 18 years were invited to undergo a gastroscopic exam. RESULTS: PCA positivity was detected in ten (4.5%) subjects (5F/5M; 12.6 ± 3.4 years). The prevalence of PCA positivity was not significantly different in the comparison of GD and AT patients (p = 0.9). PCA positivity was detected after 2.7 ± 2.7 years of follow-up in AT and 4.4 ± 4.0 years in GD (p = 0.4). Autoantibody positivity was more prevalent in female patients, in both AT and GD (p = 0.02 and p = 0.03, respectively). At detection of PCA positivity, five out of ten PCA-positive patients had iron deficiency, four vitamin B12 deficiency, two anemia, three hypergastrinemia and two elevated chromogranin values. Two patients had H. pylori infection. Gastroscopy was performed in the five ATD patients and in all patients, AIG was confirmed. CONCLUSION: In the juvenile population, ATD and AIG may also be associated. PCA screening is useful to detect subjects at risk for this condition. Due to the longer life expectancy of the pediatric population and considering the relatively high risk of malignant transformation, early surveillance monitoring is mandatory for children and adolescents with ATD.

Accuracies of Endoscopic Diagnosis of Helicobacter pylori-Gastritis: Multicenter Prospective Study Using White Light Imaging and Linked Color Imaging.

INTRODUCTION: The diagnosis of Helicobacter pylori infection status with white light imaging (WLI) is difficult. We evaluated the accuracies of using WLI and linked color imaging (LCI) for diagnosing H. pylori-active gastritis in a multicenter prospective study setting. METHODS: Patients who underwent esophagogastroduodenoscopy were prospectively included. The image collection process was randomized and anonymous, and the image set included 4 images with WLI or 4 images with LCI in the corpus that 5 reviewers separately evaluated. Active gastritis was defined as positive when there was diffuse redness in WLI and crimson coloring in LCI. The H. pylori infection status was determined by the urea breath test and the serum antibody test. Cases in which both test results were negative but atrophy or intestinal metaplasia was histologically confirmed were defined as past infections. The primary endpoint was the diagnostic accuracies of WLI and LCI, and the secondary endpoint was inter-observer agreement. RESULTS: Data for 127 patients were analyzed. The endoscopic diagnostic accuracy for active gastritis was 79.5 (sensitivity of 84.4 and specificity of 74.6) with WLI and 86.6 (sensitivity of 84.4 and specificity of 88.9) with LCI (p = 0.029). LCI significantly improved the accuracy in patients with past infections over WLI (36.8 in WLI and 78.9 in LCI, p < 0.01). The κ values were 0.59 in WLI and 0.70 in LCI. CONCLUSIONS: LCI is useful for endoscopic diagnosis of H. pylori-active or inactive gastritis, and it is advantageous for patients with past infections of inactive gastritis.

Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study.

BACKGROUND: Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools. OBJECTIVE: We aimed to develop tissue- and blood-based diagnostic platforms for EG. METHODS: Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP18 scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels. RESULTS: Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P < .0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P = .0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P < .0001), and (4) inversely correlated with gastric peak eosinophil levels (r = -0.83, P < .0001), periglandular circumferential collars (r = -0.73, P < .0001), and endoscopic nodularity (r = -0.45, P < .0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P < .0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P = .0002; serum: r = 0.54, P = .0015), and (3) inversely correlated with EGDP18 scores (plasma: r = -0.64, P = .0015; serum: r = -0.46, P = .0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P < .0001). CONCLUSION: We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease.

Serum chromogranin A level continuously rises with the progression of type 1 diabetes, and indicates the presence of both enterochromaffin-like cell hyperplasia and autoimmune gastritis.

AIMS/INTRODUCTION: The relationship of chromogranin A (CgA) levels above the normal range with various outcomes, such as glycated hemoglobin levels, enterochromaffin-like cell hyperplasia and autoimmune gastritis, was investigated in type 1 diabetes patients with special regard to the progression of comorbidities. MATERIALS AND METHODS: A cohort study on 153 type 1 diabetes patients was carried out with a prospective branch on clinical and laboratory data, and a retrospective branch on histological data obtained by gastroscopy. RESULTS: Patients with CgA levels above the upper limit of the normal range (n = 28) had significantly higher glycated hemoglobin levels (P = 0.0160) than those with CgA in the normal range (n = 125). The correlation between CgA and glycated hemoglobin was significant (P < 0.0001), but weak (R = +0.32). A slight, but steady elevation (P = 0.0410) in CgA level was observed to co-vary with the duration of type 1 diabetes. Enterochromaffin-like cell hyperplasia and autoimmune gastritis was significantly more frequent (P = 0.0087 for both) in the high CgA group. Detailed analyses on gastric tissue samples confirmed a progression of enterochromaffin-like cell hyperplasia (P = 0.0192) accompanied by CgA elevation (P = 0.0316). CONCLUSIONS: The early detection and follow up of the later progression of enterochromaffin-like cell hyperplasia and autoimmune gastritis into gastric neuroendocrine tumors, which have ~100-fold greater incidence in type 1 diabetes patients, can be achieved by assessment of CgA levels. Therefore, the use of CgA could be considered as a novel auxiliary biomarker in the care of these type 1 diabetes complications.

Is there a possible relationship between gastric intestinal metaplasia and systemic arterial stiffness?

BACKGROUND AND AIM: Helicobacter pylori (H. pylori) is closely associated with pre-neoplastic lesions such as atrophic gastritis (AG) and gastric intestinal metaplasia (GIM). The relationshionship between inflammation, hyperhomocysteinemia and arterial stiffness is of pathophysiological relevance for the development of cardiovascular disease. This study aimed to investigate the relationship between vitamin B12, folic acid, homocysteine (Hcy) and pulse wave velocity (PWV) levels in patients with GIM, AG and non-atrophic non-metaplastic chronic gastritis. PATIENTS AND METHODS: ninety-seven patients with GIM, 67 patients with AG and 69 patients with chronic gastritis were included in the study. Glucose, creatinine, total cholesterol, triglyceride, low-density lipoprotein, cholesterol, high-density lipoprotein cholesterol, vitamin B12, folic acid and Hcy levels were measured by biochemical methods. PWV and other vascular parameters were measured using the Phsyio-port AS device. MAIN RESULTS: PWV was higher in patients with GIM and AG than in controls (p < 0.05 and p < 0.05, respectively). Vitamin B12 levels were significantly lower in patients with GIM and AG than in controls (p < 0.01 and p < 0.01, respectively). Folic acid levels were significantly lower in patients with GIM than in controls (p < 0.05). Hcy levels were significantly higher in patients with GIM and AG than in controls (p < 0.001 and p < 0.05, respectively). A logistic regression analysis showed that GIM, AG and vitamin B12 deficiency were predictors for arterial stiffness. CONCLUSIONS: PWV values increased in patients with GIM and AG compared to non-atrophic non-metaplastic chronic gastritis, without different conventional cardiovascular risk factors.

The role of high sensitive C-reactive protein and histopathological evaluation in chronic gastritis patients with or without Helicobacter pylori infection.

PURPOSE: To evaluate serum levels of high-sensitivity C-reactive protein (hs-CRP) in chronic gastritis patients to predict Helicobacter pylori (HP) infection, inflammatory activity, and precancerous lesions. METHODS: A total of 811 patients with upper gastrointestinal symptoms and histopathological diagnosis of chronic gastritis were enrolled in the study. On endoscopy, five gastric biopsies were taken according to Modified Sydney protocol, which were stained with hematoxylin & eosin and Giemsa. RESULTS: HP infection was found in 28.6% of patients, being significantly more common in specimens with acute and chronic inflammatory activity. Mucosal atrophy, intestinal metaplasia, and dysplasia were found in 20.2%, 18.8% and 2.7% of biopsy specimens. Mean hs-CRP was 1.9±1.6 mg/dl for males and 2.2±1.9 mg/dl for females. hs-CRP average were significantly higher in patients with severe acute inflammation (p:0.049), in patients with severe chronic inflammation (p:0.015) and in those with HP (p: 0.001) . The severity of HP infection increased significantly with the increased degree of acute inflammation, chronic inflammation and hs-CRP level (p=0.001 for both). CONCLUSION: Serum hs-CRP level increases in patients with chronic gastritis, it could be an indicator of severity of acute or chronic mucosal inflammation, and presence of HP infection. Therefore, hs-CRP may aid the diagnosis of chronic gastritis, but it is not associated with pre-cancerous lesions.

Can neopterin be a useful immune biomarker for differentiating gastric intestinal metaplasia and gastric atrophy from non-atrophic non-metaplastic chronic gastritis?

INTRODUCTION: Helicobacter pylori (H. pylori) is closely related to pre-neoplastic lesions such as gastric atrophy (GA), gastric intestinal metaplasia (GIM) and eventually gastric cancer (GC). The diagnosis of GIM and GA is usually based on endoscopic and histopathological features. Nowadays, there are no recognized good serological markers of GIM and GA. Neopterin is an important marker of cellular inflammation. In this study, we aimed to comparatively evaluate C-reactive protein (CRP) and neopterin levels in patients with GIM, GA and chronic gastritis, and to show the increased serum neopterin levels in GIM and GA according to non-atrophic and non-metaplastic chronic gastritis. PATIENTS AND METHODS: 98 patients with GIM and 68 patients with GA and 70 patients with non-atrophic non-metaplastic gastritis were included in the study. CRP and neopterin levels were assessed in patients and controls. RESULTS: CRP and neopterin levels were significantly higher in patients with GIM and GA than in controls (p<0.05 and p<0.001, respectively). A multiple logistic regression analysis showed that high levels of serum neopterin were positively correlated with GIM and GA. According to the ROC curve analysis, the best cut-off value to differentiate between patients with GIM and/or GA from controls was ≥10.15nmol/l (p<0.001) for serum neopterin levels and ≥1.95mg/l (p<0.001) for serum CRP levels. DISCUSSION: CRP and neopterin levels are significantly increased in GIM and GA. Neopterin may be a useful biomarker and diagnostic test for detecting GIM and GA in clinical practice. CRP levels may be helpful for this observation.

Comparison of body condition score and other minimally invasive biomarkers between dogs with gastric carcinoma and dogs with chronic gastritis.

OBJECTIVE To identify minimally invasive biomarkers to help differentiate dogs with gastric carcinoma from those with chronic gastritis. DESIGN Prospective study. ANIMALS 15 dogs with gastric carcinoma, 29 dogs with chronic gastritis, and 7 healthy dogs. PROCEDURES Dogs with clinical signs of upper gastrointestinal tract disease for > 14 days that underwent gastroscopy or necropsy for collection of gastric biopsy specimens for histologic evaluation were prospectively enrolled. Gastric carcinoma and chronic gastritis were diagnosed on the basis of histologic findings. Additionally, gastric biopsy specimens were collected endoscopically from 7 healthy (control) dogs while they were anesthetized for a routine neutering procedure. Prior to being anesthetized for gastroscopy or euthanized, all dogs underwent a physical examination, and a blood sample was collected for quantification of select serum biomarker concentrations. Histologic findings, body condition score (BCS), and serum biomarker concentrations were compared among the 3 groups. RESULTS Dogs with gastric carcinoma were significantly older and had a significantly lower BCS, lower serum folate concentration, and greater serum C-reactive protein (CRP) concentration, compared with dogs with chronic gastritis and control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that age > 8 years, BCS < 4, serum CRP concentration > 25 mg/L, and an abnormally low serum folate concentration might be useful noninvasive biomarkers for identification of dogs with gastric carcinoma. For underweight older dogs with signs of upper gastrointestinal tract disease and high serum CRP and low serum folate concentrations, gastric biopsy specimens should be obtained and evaluated so that a prompt definitive diagnosis can be made and appropriate treatment initiated.

Clinical and pathological profile of eosinophilic gastroenteritis.

BACKGROUND: Eosinophilic gastroenteritis (EoGE) can be diagnosed on the basis of histologic criteria; however, the pathology is considered to be heterogeneous. There is no consensus on the management of this enigmatic disorder with an unknown etiology. PATIENTS AND METHODS: Data for patients diagnosed with EoGE and followed up over a 1-year period were analyzed. Their symptoms, patterns of flares, and type of treatment were documented. The shift in peripheral blood eosinophil levels was also examined. RESULTS: A total of 10 (mean age, 44 years; range: 31-70 years; women, 5) patients were diagnosed with EoGE. The most frequent presenting symptom was abdominal pain, and eight patients were classified with mucosal type of EoGE. Chronic disease or multiple flares were observed in seven out of 10 (70.0%) patients, and all of them had a history of allergy. Four were corticosteroid dependent (three relapsed during corticosteroid tapering and one following corticosteroid withdrawal). One of them received anti-IL5 monoclonal antibody that enabled corticosteroid dose tapering. In four patients with highly elevated initial eosinophil levels at diagnosis, the peripheral eosinophil level correlated with the amelioration and deterioration of their symptoms. The remaining three patients had a single flare without relapse. Two had no history of allergy. CONCLUSION: EoGE is a unique disorder with a variable clinical course. Although further studies are required to confirm our observations, the presence of other allergic disorders is associated with chronicity or multiple flares. Peripheral eosinophil level may be an effective biomarker for recurrence in patients with severe systemic disorders at diagnosis.

Can mean platelet volume IndIcate HelIcobacter posItIvIty and severIty of gastrIc InflammatIon? An orIgInal study and revIew of the lIterature.

Helicobacter pylori (H. pylori) is a common problem and a significant cause of chronic gastric inflammation. H. pylori, ongoing gastric inflammation and its severity are the most critical component of precursors of gastric cancer. Hypothetically, every chronic tissue injury activates platelets, and the mean platelet volume (MPV) reflects this action well. The potential relationship between H. pylori and platelet count has been shown before. However, there are few and conflicting papers about the relationship between MPV and H. pylori related chronic gastric inflammation and its severity. The study aimed to assess any potential relationship between MPV and presence of H. pylori, as well as the severity of chronic gastric inflammation. A total of 6890 endoscopic reports were initially evaluated, and a total of 218 dyspeptic patients having undergone upper endoscopy were included. Of these, 118 (54.2%) were H. pylori positive and 100 (45.8%) were H. pylori negative. At least four gastric biopsies were obtained and evaluated according to Sydney classification. Age, gender, hemoglobin, mean corpuscular volume, ferritin, serum iron and C-reactive protein, as well as endoscopic findings were also recorded. A p<0.05 was accepted as significant. The MPV and platelet count did not differ between H. pylori positive and H. pylori negative groups of patients (p>0.05). There were no differences and correlation between MPV and gastric inflammation severity according to Sydney classification (p>0.05). When stratifying MPV as <9.15 fL and >9.15 fL, there was no difference between H. pylori positive and H. pylori negative groups either (p>0.05). In this study, we found no relationship between MPV and presence of H. pylori or severity of gastric inflammation. Although there are still conflicting publications on this issue, in our opinion and according to the results of this study, MPV is not a suitable marker for evaluation of gastric inflammation severity, being H. pylori either positive or negative.

The role of high sensitive C-reactive protein and histopathological evaluation in chronic gastritis patients with or without Helicobacter pylori infection

Abstract Purpose: To evaluate serum levels of high-sensitivity C-reactive protein (hs-CRP) in chronic gastritis patients to predict Helicobacter pylori (HP) infection, inflammatory activity, and precancerous lesions. Methods: A total of 811 patients with upper gastrointestinal symptoms and histopathological diagnosis of chronic gastritis were enrolled in the study. On endoscopy, five gastric biopsies were taken according to Modified Sydney protocol, which were stained with hematoxylin & eosin and Giemsa Results: HP infection was found in 28.6% of patients, being significantly more common in specimens with acute and chronic inflammatory activity. Mucosal atrophy, intestinal metaplasia, and dysplasia were found in 20.2%, 18.8% and 2.7% of biopsy specimens. Mean hs-CRP was 1.9±1.6 mg/dl for males and 2.2±1.9 mg/dl for females. hs-CRP average were significantly higher in patients with severe acute inflammation (p:0.049), in patients with severe chronic inflammation (p:0.015) and in those with HP (p: 0.001) . The severity of HP infection increased significantly with the increased degree of acute inflammation, chronic inflammation and hs-CRP level (p=0.001 for both). Conclusion: Serum hs-CRP level increases in patients with chronic gastritis, it could be an indicator of severity of acute or chronic mucosal inflammation, and presence of HP infection. Therefore, hs-CRP may aid the diagnosis of chronic gastritis, but it is not associated with pre-cancerous lesions.

Gastroesophageal reflux disease in an area with low Helicobacter pylori infection prevalence.

The association between gastroesophageal reflux disease (GERD) prevalence and its risk factors in an area with low Helicobacter pylori prevalence is important to clarify. We analyzed the prevalence of GERD and risk factors in an area of Indonesia with low prevalence of H. pylori infection. We recruited 104 dyspeptic patients who underwent endoscopy in Surabaya. Patients were diagnosed with GERD based on the Los Angeles classification. We evaluated gastric biopsy specimens and measured serum pepsinogen levels. Interleukin polymorphisms were evaluated by polymerase chain reaction-restriction fragment length polymorphism. Of 104 patients, 56 (53.8%) were endoscopically found to have GERD, with most categorized as grade A; 48 (46.2%) were classified as non-GERD. Higher economic status, smoking, and a history of proton-pump inhibitor use significantly increased the risk of GERD. GERD Questionnaire scores showed a positive correlation with GERD (P < 0.001). An association was found between antral atrophic gastritis and GERD (P = 0.030), and patients with GERD more frequently had severe antral atrophy than nonerosive reflux disease (P = 0.018). We found an association between pepsinogen I/II levels and GERD (P = 0.047), but with low accuracy. IL-1ß -511 TT and CT were predominant among the IL-1ß -511 genotypes, and IL-8-251 AT and TT were predominant among the IL-8-251 genotypes. In conclusion, we found a high prevalence of GERD in an area with low prevalence of H. pylori infection, which could be associated with acid reflux. Smoking, history of proton-pump inhibitor use, and higher economic group significantly increased the risk of GERD.

Chronic Gastritis Due to Helicobacter Pylori Associated with Increased Serum Levels of CA54/61: A Report of Three Cases.

BACKGROUND The bacterial pathogen Helicobacter pylori (H. pylori) can cause chronic gastritis. CA54/61 is a serum tumor marker that has been shown to be positive in the several types of human malignancy. However, the association of between chronic gastritis due to H. pylori and elevated serum levels of CA54/61 has not been previously reported. This report is of three cases of increased serum levels of CA54/61 associated with H. pylori chronic gastritis. CASE REPORT Case 1 was a 44-year-old Japanese woman with a serum CA54/61 level of 138 U/ml (normal level: 12 U/ml). Following treatment and eradication of H. pylori the serum CA54/61 level decreased to 14 U/ml. Case 2 was a 73-year-old Japanese man with a serum level of less than 2 U/ml before completion of successful eradication therapy of H. pylori with a small peak of 30 U/ml after therapy. Case 3 was a 54-year-old Japanese man who maintained a serum CA54/61 level of approximately 20 U/ml before and until 603 days after eradication therapy. None of the three patients had malignancy, which is usually suggested by this serum marker. CONCLUSIONS These three case reports suggest the possibility of an association between chronic gastritis involving H. pylori infection and an elevated serum level of CA54/61. It is possible that the inflammatory gastric mucosal cells supply CA54/61 to the bloodstream. However, further studies are required to confirm the association between serum levels of CA54/61 and H. pylori chronic gastritis and the underlying mechanisms of this association.

Inflammatory mechanism of Rumenitis in dairy cows with subacute ruminal acidosis.

BACKGROUND: Subacute ruminal acidosis (SARA) is a metabolic disease in high-producing dairy cattle, and is accompanied by rumenitis. However, the mechanism of rumenitis remains unclear. Therefore, the aim of this study was to investigate the molecular mechanism of rumenitis in dairy cows with SARA. RESULTS: The results showed that SARA cows displayed high concentrations of ruminal volatile fatty acids, lactic acid and lipopolysaccharide (LPS). Furthermore, the blood concentrations of LPS and acute phase proteins haptoglobin, serum amyloid-A, and LPS binding protein were significantly higher in SARA cows than in control cows. Importantly, the phosphorylation levels of nuclear factor-kappaB (NF-κB) p65, inhibitor of NF-κB (IκB), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2) were significantly higher in the rumen epithelium of SARA cows than those of control cows. The ruminal mRNA and protein levels of NF-κB- and mitogen-activated protein kinase (MAPK)s -regulated inflammatory cytokines, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and interleukin 1ß (IL-1ß), were markedly higher in SARA cows than in control cows. Similarly, serum concentrations of TNF-α and IL-6 were also significantly higher in SARA cows. CONCLUSIONS: These results indicate that SARA results in high concentration of ruminal LPS, which over activates the NF-κB and MAPKs inflammatory pathways and then significantly increases the expression and synthesis of pro-inflammation cytokines in the rumen epithelium, thereby partly inducing rumenitis.