Aleksandra Sokic-Milutinovic

Anti-CagA and anti-VacA antibodies in Helicobacter pylori-infected patients with and without peptic ulcer disease in Serbia and Montenegro.

Background: The expression of two Helicobacter pylori proteins, CagA and VacA, is associated with more severe pathogenesis and clinical outcomes of the infection. However, this association varies among geographical regions and ethnic groups. We therefore evaluated CagA and VacA seroprevalence in H. pylori‐positive dyspeptic patients in Serbia and Montenegro. Methods: In 173 consecutive dyspeptic patients referred to endoscopy (67M, mean age 49 ± 15, 76 smokers), immunoblot assay was used to detect serum antibodies against CagA and VacA. Presence of H. pylori infection was assessed using a rapid urease test (RUT), routine histology and serology (anti‐IgG ELISA). Duodenal ulcer (DU) was diagnosed in 28, gastric ulcer (GU) in 3 and non‐ulcer dyspepsia (NUD) in the remaining 142 patients. Results: 129 (74.6%) patients were H. pylori‐positive, 27 (96.4%) with DU, 3 (100%) with GU and 99 (69.7%) with NUD (P < 0.01); 121 (93.8%) patients carried anti‐CagA antibodies and there was no difference between the DU and NUD groups. VacA antibodies were detected in sera of 50 (38.75%) and were more prevalent in patients with DU compared to the NUD group (P < 0.05). Conclusions: In Serbia and Montenegro there is high seroprevalence of CagA‐positive H. pylori strains in dyspeptic patients with and without peptic ulcer, while VacA‐positive strains are more closely related to peptic ulcer disease.

Role of Helicobacter pylori infection in gastric carcinogenesis: Current knowledge and future directions

Helicobacter pylori (H. pylori) plays a role in the pathogenesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a multistep process that is reversible in the early phase of mucosal damage, but the exact point of no return has not been identified. Therefore, two main therapeutic strategies could reduce gastric cancer incidence: (1) eradication of the already present infection; and (2) immunization (prior to or during the course of the infection). The success of a gastric cancer prevention strategy depends on timing because the prevention strategy must be introduced before the point of no return in gastric carcinogenesis. Although the exact point of no return has not been identified, infection should be eradicated before severe atrophy of the gastric mucosa develops. Eradication therapy rates remain suboptimal due to increasing H. pylori resistance to antibiotics and patient noncompliance. Vaccination against H. pylori would reduce the cost of eradication therapies and lower gastric cancer incidence. A vaccine against H. pylori is still a research challenge. An effective vaccine should have an adequate route of delivery, appropriate bacterial antigens and effective and safe adjuvants. Future research should focus on the development of rescue eradication therapy protocols until an efficacious vaccine against the bacterium becomes available.

Variations in inflammatory genes as molecular markers for prediction of inflammatory bowel disease occurrence.

Research on inflammatory bowel disease (IBD) has highlighted genes involved in the regulation of inflammatory responses as contributors to disease pathogenesis. This study aimed to evaluate the associations between IBD and variations in NOD2, TLR4, TNF‐α, IL‐6, IL‐1β and IL‐1RN genes, and to use the genetic data obtained in predictive modeling.

Epidemiological Trends in Stomach-Related Diseases

Epidemiology is a study of disease variations by geography, population demographics and time. Temporal influences can manifest themselves as age effects, period effects, cohort effects, seasonal or monthly variations. The acquisition of Helicobacter pylori infection during early childhood and the ensuing risk for the future development of peptic ulcer or gastric cancer represents a typical example for a cohort effect in digestive diseases. The incidence and prevalence of uncomplicated peptic ulcer have decreased in recent years, largely because of the availability of treatment to eradicate H. pylori and the decreasing prevalence of H. pylori infection. Nowadays, gastric and duodenal ulcers tend to occur in older people, who were more likely to have been exposed to H. pylori in their childhood than recently born generations. The overall incidence of gastric cancers is declining; however, there has been a relative increase in the incidence of tumors of the esophagogastric junction and gastric cardia. Thus, by extrapolating the strong, stable and consistent mortality rate declines in recent decades, gastric cancer was projected to become increasingly less important as a cause of death in Europe in the next decades.

Capsule endoscopy is useful diagnostic tool for diagnosing Meckel's diverticulum.

Objective Meckel’s diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract. Although a majority of patients remain asymptomatic, complications may occur in a subset of patients. MD is a rare cause of gastrointestinal bleeding (GIB) in adults. We aimed to clarify the possible role of capsule endoscopy (CE) in the identification of Meckel’s diverticulum. Patients and methods From October 2004 to December 2010, 157 CEs were performed (83 male individuals, mean age 51±20 years; range 3–83 years) for obscure GIB. Before CE, all patients underwent nonconclusive upper and lower endoscopy at least two times and barium follow-through. Results CE identified the source of bleeding in 70/157 patients (44.6%). MD was diagnosed in 13/70 (18.6%) patients (11 male individuals, mean age 35±20 years, range, 3–69 years) after CE. Nine patients presented with obscure overt and four with obscure occult bleeding. The mean duration of obscure GIB history was 13 months (range 1–72 months). The mean hemoglobin concentration at the time of the procedure was 115±12 g/l. The findings of MD on CE were double lumen sign (13/13), visible blood (7/13), and diaphragm sign (6/13). All patients were operated upon, and MD histologically verified in 11. In two patients CE was false-positive and in two patients, false-negative. Capsule endoscopy had a positive predictive value of 84.6% for the diagnosis of MD. Conclusion MD should be considered in the differential diagnosis of obscure GIB in adults. CE is an effective and promising modality for diagnosing MD in patients with obscure GIB.

Genetic and environmental factors significant for the presentation and development of inflammatory bowel disease

Objectives The aim of the study was to evaluate associations between inflammatory bowel disease (IBD) presentation and variants in NOD2, TLR4, TNF-&agr;, IL-6, IL-1&bgr;, and IL-RN genes in order to identify possible environmental factors that may affect IBD occurrence, investigate potential predictors for surgical treatment of IBD, and correlate the presence of granulomas in biopsy specimens with clinical characteristics of Crohn’s disease (CD) patients. Patients and methods We genotyped 167 IBD patients using PCR-based methodology and tested for disease genotype–phenotype associations. Results In CD patients ileal localization of disease was more frequent in NOD2 variant carriers. Ileal CD was associated with IL-6 GC+CC genotypes, identifying C allele as a possible marker of increased risk for ileal CD. In CD patients a positive family history for IBD was related to earlier onset of disease, higher risk for CD-related surgery, and appendectomy. CD patients who are TLR4 299Gly carriers are at higher risk for surgery at onset of the disease compared with TLR4 299Asp variant carriers. The presence of granuloma in biopsy specimens was more frequent in patients in whom a diagnosis of CD was made during emergency surgery. Multivariate analysis showed that CD carriers of the 299Gly allele had a 4.6-fold higher risk for emergency surgery before CD diagnosis is established compared with noncarriers, suggesting an aggressive disease course. Granuloma in endoscopic biopsies is detected 5.4-fold more frequently in patients treated surgically at the time of diagnosis. Conclusion Genetic variants together with epidemiological and clinical data of IBD patients could potentially be used as predictors of the disease course.

Importance of TLR9-IL23-IL17 axis in inflammatory bowel disease development: Gene expression profiling study

BACKGROUND AND AIMS Mucosal gene expression have not been fully enlightened in inflammatory bowel disease (IBD). Aim of this study was to define IL23A, IL17A, IL17F and TLR9 expression in different IBD phenotypes. METHODS Evaluation of mRNA levels was performed in paired non-inflamed and inflamed mucosal biopsies of newly diagnosed 50 Crohns disease (CD) and 54 ulcerative colitis (UC) patients by quantitative real-time PCR analysis. RESULTS IL17A and IL17F expression levels were significantly increased in inflamed IBD mucosa. Inflamed CD ileal and UC mucosa showed increased IL23A, while only inflamed CD ileal samples showed increased TLR9 mRNA level. Correlation between analysed mRNAs levels and endoscopic and clinical disease activity were found in UC, but only with clinical activity in CD. CONCLUSION Both CD and UC presented expression of Th17-associated genes. Nevertheless, expression profiles between different disease forms varies which should be taken into account for future research and therapeutics strategies.

Recommendation for gastroprotection in gastrointestinal bleeding prevention

Incidence of gastrointestinal bleeding in most populations is about 1 per 1,000 inhabitants. More than 65% of all bleeding episodes are associated with drug use. The most often involved are non-steroidal antiinflammatory drugs and low doses of acetyl-salicylic acid. The mortality within the first month after the bleeding episode is about 10–12%, and has not significantly changed in the last decade. Therefore, bleeding prevention is of major importance. Appropriate selection of patients, proper drug choice, application of lowest efficient doses of potentially ulcerogenic drugs, and use of drugs that inhibit gastric acid secretion remain cornerstone preventive measures of gastrointestinal bleeding.