Laimas Jonaitis

Initial disease course and treatment in an inflammatory bowel disease inception cohort in Europe: The ECCO-EpiCom cohort

Background:The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort. Methods:Patients were followed-up every third month during the first 12 (±3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu). Results:In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn’s disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe. Discussion:In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.

Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

BackgroundSeveral polymorphisms of genes involved in the immunological recognition of Helicobacter pylori and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding Angiotensin converting enzyme (ACE), Nod-like receptor 1 (NOD1), Toll-like receptor 4 (TLR4) and FAS/FASL.MethodsGene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. ACE I/D (rs4646994), NOD1 796G>A (rs5743336), TLR4 3725G>C (rs11536889), FAS 1377G>A (rs2234767), FAS 670A>G (rs1800682) and FASL 844T>C (rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis.ResultsFrequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for NOD1 796G/G genotype to be associated with increased risk of HRAG (62.4% vs. 54.5% in controls, p = 0.082). FAS 670G/G genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (p = 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. NOD1 796G>A and TLR4 3725G>C gene polymorphisms were also not associated with Helicobacter pylori infection.ConclusionsACE, NOD1, TRL4 and FAS/FASL gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.

Efficacy of the natural antioxidant astaxanthin in the treatment of functional dyspepsia in patients with or without Helicobacter pylori infection: A prospective, randomized, double blind, and placebo-controlled study

OBJECTIVES The aim of this study was to evaluate the efficacy of the natural antioxidant astaxanthin in functional dyspepsia in different doses and compared with placebo. DESIGN The study was a controlled, prospective, randomized, and double blind trial. PARTICIPANTS Patients with functional dyspepsia, divided into three groups with 44 individuals in each group (placebo, 16mg, or 40mg astaxanthin, respectively). INTERVENTIONS Participants were asked to accept gastroscopy before treatment, together with questionnaires: GSRS and SF-36. Urea breath test (UBT) was done before the treatment. MAIN OUTCOME The primary objective was to test the hypothesis that the antioxidant astaxanthin at two doses regimens compared to placebo should ameliorate gastrointestinal discomfort measured as GSRS in patients with functional dyspepsia, who were either positive or negative for Helicobacter pylori, after 4 weeks of treatment. RESULTS At the end of therapy (week 4) no difference between the three treatment groups was observed regarding mean Gastrointestinal Symptom Rating Scale (GSRS) scores of abdominal pain, indigestion and reflux syndromes. The same results were observed at the end of follow-up. However reduction of reflux syndrome before treatment to week 4 was significantly pronounced in the higher (40mg) dose compared to the other treatment groups (16mg and placebo, p=0.04). CONCLUSION In general, no curative effect of astaxanthin was found in functional dyspepsia patients. Significantly greater reduction of reflux symptoms were detected in patients treated with the highest dose of the natural antioxidant astaxanthin. The response was more pronounced in H. pylori-infected patients.

Costs and resource utilization for diagnosis and treatment during the initial year in a European inflammatory bowel disease inception cohort : an ECCO-EpiCom Study

Background:No direct comparison of health care cost in patients with inflammatory bowel disease across the European continent exists. The aim of this study was to assess the costs of investigations and treatment for diagnostics and during the first year after diagnosis in Europe. Methods:The EpiCom cohort is a prospective population-based inception cohort of unselected inflammatory bowel disease patients from 31 Western and Eastern European centers. Patients were followed every third month from diagnosis, and clinical data regarding treatment and investigations were collected. Costs were calculated in euros (&OV0556;) using the Danish Health Costs Register. Results:One thousand three hundred sixty-seven patients were followed, 710 with ulcerative colitis, 509 with Crohns disease, and 148 with inflammatory bowel disease unclassified. Total expenditure for the cohort was &OV0556;5,408,174 (investigations: &OV0556;2,042,990 [38%], surgery: &OV0556;1,427,648 [26%], biologicals: &OV0556;781,089 [14%], and standard treatment: &OV0556;1,156,520 [22%)]). Mean crude expenditure per patient in Western Europe (Eastern Europe) with Crohns disease: investigations &OV0556;1803 (&OV0556;2160) (P = 0.44), surgery &OV0556;11,489 (&OV0556;13,973) (P = 0.14), standard treatment &OV0556;1027 (&OV0556;824) (P = 0.51), and biologicals &OV0556;7376 (&OV0556;8307) (P = 0.31). Mean crude expenditure per patient in Western Europe (Eastern Europe) with ulcerative colitis: investigations &OV0556;1189 (&OV0556;1518) (P < 0.01), surgery &OV0556;18,414 (&OV0556;12,395) (P = 0.18), standard treatment &OV0556;896 (&OV0556;798) (P < 0.05), and biologicals &OV0556;5681 (&OV0556;72) (P = 0.51). Conclusions:In this population-based unselected cohort, costs during the first year of disease were mainly incurred by investigative procedures and surgeries. However, biologicals accounted for >15% of costs. Long-term follow-up of the cohort is needed to assess the cost-effectiveness of biological agents.

Lack of association between miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 gene polymorphisms and colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide with high mortality rates. MicroRNAs (miRNAs) have an established role in the development of different cancers. Single nucleotide polymorphisms (SNPs) in miRNA related genes were linked with various gastrointestinal malignancies. However, the data on association between miRNA SNPs and CRC development are inconsistent. The aim of the present study was to evaluate the association between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608) and the presence of CRC in European population. Gene polymorphisms were analyzed in 621 subjects (controls: n = 428; CRC: n = 193). MiR-27a T>C (rs895819), miR-146a G>C (rs2910164), miR-196a-2 C>T (rs11614913), miR-492 G>C (rs2289030) and miR-608 C>G (rs4919510) SNPs were genotyped by RT-PCR. Overall, all genotypes and alleles of miRNA SNPs were distributed equally between control and CRC groups. We observed a tendency for miR-146a C allele to be associated with lower risk of CRC when compared to G allele, however, the difference did not reach the adjusted P-value (odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.49–0.95, P = 0.025). In conclusion, gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of CRC in European subjects.

Laryngeal examination is superior to endoscopy in the diagnosis of the laryngopharyngeal form of gastroesophageal reflux disease

Objective. The laryngopharyngeal form of gastroesophageal reflux disease (LF GERD) is a frequent manifestation of supraesophageal GERD. Diagnosis of LF GERD is difficult: most of the common diagnostic methods of GERD have insufficient accuracy in establishing LF GERD. The purpose of this study was to evaluate the role of endoscopic and laryngologic examination in the diagnosis of LF GERD and to create a laryngoscopic reflux index (LRI). Material and methods. A total of 108 LF GERD patients and 90 controls were investigated. The criteria for LF GERD were: complaints, reflux-laryngitis, and esophagitis (endoscopically or histologically proven). Lesions in four laryngeal regions were evaluated: arytenoids (A), intraarytenoid notch (IAN), vestibular folds (VF), and vocal cords (VC). Three types of mucosal lesions were evaluated on a points basis: alterations of the epithelium, erythema, and edema. Total LRI was calculated by summing-up the indices in the separate laryngeal areas. Results. The LRI mean value (11.48±3.78 points) of LF GERD patients was statistically significantly greater than that (1.64±1.93 points) of the controls. The most significant laryngoscopic changes of LF GERD were: mucosal lesions of IAN, mucosal lesions of VC, and edema of VC. A combination of these three findings reliably distinguishes the LF GERD patients from controls in 95.9% of cases. The mucosal lesions of IAN have the greatest importance in diagnosing LF GERD: the odds ratio to LF GERD – 21.32, p<0.001. Endoscopic esophagitis was established in 36 (33.3%) cases. The severity of esophagitis did not correlate with the severity of the laryngeal findings. Conclusions. Laryngoscopy is superior to endoscopy in diagnosing LF GERD. Endoscopy has limited value in the diagnosis of LF GERD. Establishing the LRI could be helpful in the differential diagnosis of the disease in the everyday clinical practice.

Analysis of Deregulated microRNAs and Their Target Genes in Gastric Cancer.

Background MicroRNAs (miRNAs) are widely studied non-coding RNAs that modulate gene expression. MiRNAs are deregulated in different tumors including gastric cancer (GC) and have potential diagnostic and prognostic implications. The aim of our study was to determine miRNA profile in GC tissues, followed by evaluation of deregulated miRNAs in plasma of GC patients. Using available databases and bioinformatics methods we also aimed to evaluate potential target genes of confirmed differentially expressed miRNA and validate these findings in GC tissues. Methods The study included 51 GC patients and 51 controls. Initially, we screened miRNA expression profile in 13 tissue samples of GC and 12 normal gastric tissues with TaqMan low density array (TLDA). In the second stage, differentially expressed miRNAs were validated in a replication cohort using qRT-PCR in tissue and plasma samples. Subsequently, we analyzed potential target genes of deregulated miRNAs using bioinformatics approach, determined their expression in GC tissues and performed correlation analysis with targeting miRNAs. Results Profiling with TLDA revealed 15 deregulated miRNAs in GC tissues compared to normal gastric mucosa. Replication analysis confirmed that miR-148a-3p, miR-204-5p, miR-223-3p and miR-375 were consistently deregulated in GC tissues. Analysis of GC patients’ plasma samples showed significant down-regulation of miR-148a-3p, miR-375 and up-regulation of miR-223-3p compared to healthy subjects. Further, using bioinformatic tools we identified targets of replicated miRNAs and performed disease-associated gene enrichment analysis. Ultimately, we evaluated potential target gene BCL2 and DNMT3B expression by qRT-PCR in GC tissue, which correlated with targeting miRNA expression. Conclusions Our study revealed miRNA profile in GC tissues and showed that miR-148a-3p, miR-223-3p and miR-375 are deregulated in GC plasma samples, but these circulating miRNAs showed relatively weak diagnostic performance as sole biomarkers. Target gene analysis demonstrated that BCL2 and DNMT3B expression in GC tissue correlated with their targeting miRNA expression.

Interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms are not associated with premalignant gastric conditions: a combined haplotype analysis.

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.

Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with Inflammatory Bowel Disease — An ECCO-EpiCom study☆

BACKGROUND & AIMS Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe. METHODS The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up. RESULTS In total, 1079 patients were included in this study. Crohns disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population. CONCLUSION Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

A 1 year follow-up study of the consequences of Helicobacter pylori eradication in duodenal ulcer patients: unchanged frequency of erosive oesophagitis and decreased prevalence of non-erosive gastro-oesophageal reflux disease.

Background and aim Discussions concerning the increased incidence of gastro-oesophageal reflux disease (GORD) after Helicobacter pylori eradication continue. In this study we aimed to evaluate the presence of co-existing GORD in (1) duodenal ulcer patients after successful H. pylori eradication, (2) patients with persistent H. pylori infection after attempts at eradication, and (3) controls in whom H. pylori eradication had not been attempted. Methods A prospective study of 255 patients with duodenal ulcer who were assigned to H. pylori eradication or to control treatment (omeprazole for 4 weeks) and followed up for 1 year or until peptic ulcer relapse. GORD was determined in the patients who had reflux oesophagitis on endoscopy at the beginning of the study and/or in patients without reflux oesophagitis if they experienced heartburn and/or regurgitation at least twice a week associated with impairment of daily activities. Results The study revealed a significant decrease (from 44.6% to 21.7%; P < 0.001) of patients with GORD at the end of the follow-up among those in whom H. pylori eradication had been successful. There was no significant difference in the frequency of reflux oesophagitis before and after the follow-up regardless of H. pylori status. Conclusions H. pylori eradication did not significantly influence the prevalence and incidence of reflux oesophagitis in patients with duodenal ulcer during a 1 year follow-up period, but there was a significantly lower prevalence of GORD after successful H. pylori eradication, as patients with non-erosive GORD had been cured.