Endoscopic indicators in patients with familial adenomatous polyposis undergoing duodenal resections - a nationwide Danish cohort study with long-term follow-up.

BACKGROUND: Familial adenomatous polyposis (FAP) predisposes individuals to duodenal adenomas. This study describes the histopathological features of endoscopic and surgical specimens from the duodenum, as well as genotype-phenotype associations. METHODS: All known FAP patients were included from the Danish Polyposis Register. FAP patients were defined as having more than 100 cumulative colorectal adenomas and/or having a known germline pathogenic variant in the APC gene. Endoscopic procedures, histopathology, and genetics were evaluated. RESULTS: Of 500 FAP patients, 70.6% underwent esophagogastroduodenoscopy (EGD) at least once. Of these, 59.2% presented with detectable duodenal adenomas. The most severe morphology was tubular in 62.7% patients, tubulovillous in 25.4%, and villous in 12.0%, while the most severe dysplasia was low-grade in 67.5% patients, high-grade in 25.4%, and 6.7% had adenocarcinoma. In 6.2% of FAP patients, duodenal resection was recommended, including 29% with duodenal adenocarcinoma. The risk of duodenal surgery was 1.31 per 1,000 person-years (median age: 53 years). The predominant reason for surgery was extensive polyposis (67.7%). Of the patients who underwent duodenal resection, a median of six (IQR: 4-8) EGDs were performed within five years prior to surgery, but 67.6% and 83.9% never underwent a duodenal polypectomy or endoscopic mucosa resection, respectively. Of note, seventeen of 500 patients (3.4%) developed duodenal adenocarcinoma, of which 47% were advanced at diagnosis. Genetic evaluations revealed various pathogenic variants in the APC gene, with no strong genotype-phenotype association. CONCLUSIONS: The prevalence of duodenal adenomas and cancer in FAP warrants vigilant endoscopic surveillance. Nevertheless, the need for duodenal surgery persists and should together with endoscopic practice be monitored in national registers.

Disease course and treatment outcomes of Crohn's disease patients with early or late surgery - A Danish nationwide cohort study from 1997 to 2015.

BACKGROUND: Studies on early surgery among Crohn's disease patients are few and focus on ileocolonic resections. AIM: The aim of this nationwide cohort study was to investigate the disease course in all Crohn's disease patients who underwent early and late major abdominal surgery. METHODS: In a Danish nationwide cohort of Crohn's disease patients from 1997 to 2015 we included 493 patients (group 1) resected within 29 days, 472 patients (group 2) resected between 30 and 180 days, and 1,518 patients (group 3) resected after 180 days of diagnosis. Re-operation, hospitalisations and medications were analysed. RESULTS: The cumulative risk of re-operation was lower among patients from group 1 (five-year risk: 16.5% vs. group 2: 18.2% and group 3: 21.2%, p = 0.004). Fewer patients from group 2 and 3 required hospitalisations (269 (56.5%) and 803 (52.8%) vs. group 1: 329 (66.8%) p<0.001). Patients from group 3 had a higher cumulative use of immunomodulators in the first three years after initial surgery (one-year risk: 24.6% vs. group 1: 19.4% and group 2: 17.0%, p<0.001). CONCLUSION: Crohn's disease patients resected within 29 days of diagnosis had a lower cumulative risk of re-operation and a lower cumulative exposure to immunomodulators in the initial years after surgery.

The Incidence and Disease Course of Perianal Crohn's Disease: A Danish Nationwide Cohort Study, 1997-2015.

BACKGROUND AND AIMS: Perianal Crohn's disease [CD] places a considerable burden on patients' quality of life and is complex to treat. Despite its impact and high frequency, few studies have investigated the incidence and disease course of perianal CD. The aim of this study was to assess the incidence and disease course of perianal CD in adult patients throughout a 19-year period. METHODS: The cohort comprised all individuals aged 18 years or older who were diagnosed with CD in Denmark between January 1, 1997, and December 31, 2015, according to the National Patient Registry [NPR]. RESULTS: A total of 1812 [19%] out of 9739 patients with CD were found to have perianal CD. Perianal fistulas were the most common manifestation, accounting for 943 [52%] cases. The incidence of perianal CD remained stable over time. Patients with perianal CD were found to have an increased risk of undergoing major abdominal surgery compared with patients without perianal CD (hazard ratio: 1.51, 95% confidence interval [CI]: 1.40 to 1.64, p <0.001) in a multivariate Cox regression analysis. The incidence rate ratios of anal and rectal cancer in perianal CD patients were 11.45 [95% CI: 4.70 to 27.91, p <0.001] and 2.29 [95% CI: 1.25 to 4.20, p = 0.006], respectively, as compared with non-IBD matched controls. CONCLUSIONS: In this nationwide study, 19% of CD patients developed perianal disease. Patients with perianal CD were at increased risk of undergoing major surgery compared with non-perianal CD patients. The risk of anal and rectal cancer was increased in patients with perianal CD compared with non-IBD matched controls. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Dietary risk factors for inflammatory bowel diseases in a high-risk population: Results from the Faroese IBD study.

Background: The Faroe Islands currently have the highest recorded inflammatory bowel disease (IBD) incidence in the world. Objective: This study investigated environmental risk factors for IBD in the Faroese population. Methods: Environmental exposure data including lifestyle risk factors and neurotoxicants collected for over 30 years were retrieved from the Children's Health and the Environment in the Faroes (CHEF) cohorts including mainly mother-child pairs, with exposure data collected from pregnant mothers. For lifestyle risk factors, the incidence of IBD and ulcerative colitis (UC) was calculated as the rate ratio (RR) with 95% confidence intervals (CI) in exposed versus non-exposed persons. For neurotoxicants RR was calculated for persons with high versus low exposure. Results: Six cohorts included 5698 persons with complete follow-up data and at least one exposure, and 37 were diagnosed with IBD. For pilot whale/blubber, the RR was 1.02 (95% CI, 0.48-2.18); RR of 1.01 for fish (95% CI, 0.35-2.91); and of the pollutants studied, a statistical significantly increased risk was found for 1,1,1,-trichloro-2,2-bis-(p-chlorophenyl) ethane (p,p'-DDT); RR 3.04 (95% CI, 1.12-8.30). RRs were 1.96 (95% CI, 1.03-3.73) for smoking and 1.10 (95% CI, 0.55-2.19) for alcohol intake. Conclusion: The high IBD incidence is unlikely to be caused by special dietary habits or by environmental pollutants.

The Pathogenesis of Extraintestinal Manifestations: Implications for IBD Research, Diagnosis, and Therapy.

This article reports on the sixth scientific workshop of the European Crohn's and Colitis Organisation [ECCO] on the pathogenesis of extraintestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. This paper has been drafted by 15 ECCO members and 6 external experts [in rheumatology, dermatology, ophthalmology, and immunology] from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search, the supporting text was finalized under the leadership of the heads of the working groups before being integrated by the group consensus leaders.

Changes in Disease Behaviour and Location in Patients With Crohn's Disease After Seven Years of Follow-Up: A Danish Population-based Inception Cohort.

BACKGROUND AND AIM: Crohn's disease [CD] is a progressive inflammatory bowel disease that can lead to complications such as strictures or penetrating disease, and ultimately surgery. Few population-based studies have investigated the predictors for disease progression and surgery in CD according to the Montreal classification. We aimed to identify clinical predictors associated with complicated CD in a Danish population-based inception cohort during the biologic era. METHODS: All incident patients with CD in a well-defined Copenhagen area, between 2003 and 2004, were followed prospectively until 2011. Disease progression was defined as the development of bowel stricture [B2] or penetrating disease [B3] in patients initially diagnosed with non-stricturing/non-penetrating disease [B1]. Associations between disease progression and/or resection, and multiple covariates, were investigated by Cox regression analyses. RESULTS: In total, 213 CD patients were followed. A total of 177 [83%] patients had B1 at diagnosis. Patients who changed location had increased risk of disease progression (hazard ratio [HR] = 3.1, 95% CI: 1.12,8.52). Biologic treatment was associated with lower risk of change in location [HR = 0.3, 95% CI: 0.1-0.7]. Colonic involvement [L2 or L3 vs L1] was associated with a lower risk of surgery (HR = 0.34/0.22, 95% CI: [0.13,0.86]/[0.08,0.60]). All CD patients who progressed in behaviour or changed location had an increased risk of surgery [p < 0.05]. CONCLUSIONS: This population-based inception cohort study demonstrates that changes in disease location or behaviour in patients with CD increase their risk of resection. Our findings highlight the protective effect of biologic treatment with regard to change in disease location, which might ultimately improve the disease course for CD patients.

Systematic review and meta-analysis: assessment of factors affecting disability in inflammatory bowel disease and the reliability of the inflammatory bowel disease disability index.

BACKGROUND: The Inflammatory Bowel Disease Disability Index (IBD-DI) has recently been developed for patients with Crohn's disease (CD) and ulcerative colitis (UC). AIM: To assess the severity of disability and associated factors using the IBD-DI, and review the validity of the IBD-DI as a tool. METHOD: Systematic review of cross-sectional studies. Patients included had UC or CD and were classified as active, in remission, or needing surgery, biological and/or steroid treatment. We included studies assessing disability using the IBD-DI and that were captured by electronic and manual searches (January 2017). The possibility of bias was evaluated with the Newcastle-Ottawa Scale. RESULTS: Nine studies were included with 3167 patients. Comparatively, patients with active disease had higher disability rates than those in remission (SMD [CI95] = 1.49[1.11, 1.88], I2  = 94%, P<.01), while patients on biological treatment had lower disability rates than those receiving corticosteroid treatment (SMD [CI95] = -0.22[-0.36, -0.08], I2  = 0%, P<.01). Disease activity and unemployment were found to be associated factors. The IBD-DI scored "good" for internal consistency, "fair" to "excellent" for intra-rater reliability and "excellent" for inter-rater reliability. Construct validity was "moderately strong" to "very strong" and structural validity was found to be mainly unidimensional. The IBD-DI had excellent responsiveness, while its interpretability was only useful on a group level. CONCLUSIONS: This systematic review and meta-analysis found a significant association between disease activity, treatment received and disability; although significant heterogeneity was found. The IBD-DI is reliable and valid, but further studies are needed to measure its interpretability.

Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy.

Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6 and interferon gamma (IFN-γ), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P<0.05). Only the association with heterozygous genotype of IL12B (rs3212217) (OR: 0.24, 95% CI: 0.11-0.53, P=0.008) among patients with UC withstood Bonferroni correction for multiple testing. In conclusion, Our results suggest that SNPs associated with genetically determined high activity of TLR5 among patients with CD and genetically determined high IL-12 and IL-18 levels among patients with UC were associated with non-response. Further studies will evaluate whether these genes may help stratifying patients according to the expected response to anti-TNF treatment.

Systematic review with meta-analysis: proximal disease extension in limited ulcerative colitis.

BACKGROUND: Disease extent in ulcerative colitis is one of the major factors determining prognosis over the long-term. Disease extent is dynamic and a proportion of patients presenting with limited disease progress to more extensive forms of disease over time. AIM: To perform a systematic review and meta-analysis of epidemiological studies reporting on extension of ulcerative colitis to determine frequency of disease extension in patients with limited ulcerative colitis at diagnosis. METHODS: We performed a systematic literature search to identify studies on disease extension of ulcerative colitis (UC) and predictors of disease progression. RESULTS: Overall, 41 studies were eligible for systematic review but only 30 for meta-analysis. The overall pooled frequency of UC extension was 22.8% with colonic extension being 17.8% at 5 years and 31% at 10 years. Extension was 17.8% (95% CI 11.2-27.3) from E1 to E3, 27.5% (95% CI 7.6-45.6) from E2 to E3 and 20.8% (95% CI 11.4-26.8) from E1 to E2. Rate of extension was significantly higher in patients younger than 18 years (29.2% (CI 6.4-71.3) compared to older patients (20.2% (CI 13.0-30.1) (P<.0001). Risk of extension was significantly higher in patients from North America (37.8%) than from Europe (19.6%) (P<.0001). CONCLUSIONS: In this meta-analysis, approximately one quarter of patients with limited UC extend over time with most extension occurring during the first 10 years. Rate of extension depends on age at diagnosis and geographic origin. Predicting those at high risk of disease extension from diagnosis could lead to personalised therapeutic strategies.

Inflammatory bowel diseases in Faroese-born Danish residents and their offspring: further evidence of the dominant role of environmental factors in IBD development.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) is record high in the Faroe Islands, and many Faroese emigrate to Denmark, where the IBD incidence is considerably lower. AIM: To study the IBD incidence in first-, second- and third-generation immigrants from the Faroe Islands to Denmark to assess the extent to which the immigrants adopt the lower IBD incidence of their new home country. METHODS: Data on Faroese-born Danish residents and their children were retrieved from the Danish Central Population Register for 1980-2014. Incident IBD cases were identified from the Danish National Patient Register. Standardised Incidence Ratios (SIRs) were used to compare the IBD risk in immigrants with that of Danes. 95% confidence intervals (CI) were calculated using the square-root transform. RESULTS: First-generation Faroese immigrants had a higher IBD incidence than Danes, SIR 1.25 (95% CI, 0.97-1.59) for men and 1.28 (95% CI, 1.05-1.53) for women. This excess risk derived from ulcerative colitis (UC), SIR 1.44 (95% CI, 1.10-1.87) for men and 1.36 (95% CI, 1.09-1.68) for women. No excess risk was found for Crohn's disease (CD). The UC risk was nearly doubled during the immigrants' first 10 years in Denmark; SIR 2.13 (95% CI, 1.52-2.92) for men and 1.63 (95% CI, 1.19-2.18) for women. CONCLUSIONS: Although some impact of genetic dilution cannot be excluded, our findings indicate importance of gene-environment interplay in UC, as the excess UC risk in Faroese immigrants to Denmark disappeared over time and over one generation in men and over two generations in women.

The incidence of inflammatory bowel disease in Denmark 1980-2013: a nationwide cohort study.

BACKGROUND: Globally, the incidence rates of inflammatory bowel disease (IBD) are increasing; however, data from high-incidence areas are conflicting. Previous studies in Denmark have assessed incidence rates of Crohn's disease (CD) and ulcerative colitis (UC) using short observation periods. AIM: To investigate trends in IBD incidence in Denmark over a thirty-year period using nationwide data. METHODS: Patients diagnosed with CD or UC in Denmark between 1980 and 2013 were identified in the Danish National Patient Registry (NPR) and included in a nationwide cohort. Incidence rates estimated using different numbers of National Patient Registry records (≥1, 2, 3 or 4) required for case definition were compared. RESULTS: From 1980 to 2013 the incidence of CD increased from 5.2 (95% CI: 5.0-5.4) per 100 000 to 9.1 (95% CI: 8.7-9.5) per 100 000 and the incidence of UC increased from 10.7 (95% CI: 10.4-11.0) per 100 000 to 18.6 (95% CI: 18.0-19.2) per 100 000. The increased incidence in CD and UC was independent of gender. The annual increase in incidence rate was greatest in patients aged <15 years for CD and those older than 15 years for UC. For both CD and UC the incidence rates for females were significantly higher than for males. The number of registry records chosen to define IBD cases greatly influenced incidence estimates. CONCLUSIONS: The incidence of IBD in Denmark continues to increase and is among the highest in the world. Using at ≥2 records of IBD diagnosis in the Danish National Patient Registry will result in more valid incidence estimates.

Treatment Steps, Surgery, and Hospitalization Rates During the First Year of Follow-up in Patients with Inflammatory Bowel Diseases from the 2011 ECCO-Epicom Inception Cohort.

BACKGROUND AND AIMS: The ECCO-EpiCom study investigates the differences in the incidence and therapeutic management of inflammatory bowel diseases [IBD] between Eastern and Western Europe. The aim of this study was to analyse the differences in the disease phenotype, medical therapy, surgery, and hospitalization rates in the ECCO-EpiCom 2011 inception cohort during the first year after diagnosis. METHODS: Nine Western, five Eastern European centres and one Australian centre with 258 Crohn's disease [CD], 380 ulcerative colitis [UC] and 71 IBD unclassified [IBDU] patients [female/male: 326/383; mean age at diagnosis: 40.9 years, SD: 17.3 years] participated. Patients' data were registered and entered in the web-based ECCO-EpiCom database [www.epicom-ecco.eu]. RESULTS: In CD, 36 [19%] Western Europe/Australian and 6 [9%] Eastern European patients received biological therapy [p = 0.04], but the immunosuppressive [IS] use was equal and high in these regions [Eastern Europe vs Western Europe/Australia: 53% vs 45%; p = 0.27]. Surgery was performed in 17 [24%] CD patients in Eastern Europe and 13 [7%] in Western Europe/Australia [p < 0.001, pLogRank = 0.001]. Of CD patients from Eastern Europe, 24 [34%] were hospitalized, and 39 [21%] from Western Europe/Australia, [p = 0.02, pLogRank = 0.01]. In UC, exposure to biologicals and colectomy rates were low and hospitalization rates did not differ between these regions during the 1-year follow-up period [16% vs 16%; p = 0.93]. CONCLUSIONS: During the first year after diagnosis, surgery and hospitalization rates were significantly higher in CD patients in Eastern Europe compared with Western Europe/Australia, whereas significantly more CD patients were treated with biologicals in the Western Europe/Australian centres.

Incidence and initial disease course of inflammatory bowel diseases in 2011 in Europe and Australia: results of the 2011 ECCO-EpiCom inception cohort.

BACKGROUND AND AIMS: The aim of the present study was to validate the IBD (inflammatory bowel diseases) incidence reported in the 2010 ECCO-EpiCom (European Crohn's and Colitis Organization-Epidemiological Committee) inception cohort by including a second independent inception cohort from participating centers in 2011 and an Australian center to investigate whether there is a difference in the incidence of IBD between Eastern and Western European countries and Australia. METHODS: Fourteen centers from 5 Eastern and 9 Western European countries and one center from Australia participated in the ECCO-EpiCom 2011 inception cohort. Patients' data regarding disease type, socio-demographic factors, extraintestinal manifestations and therapy were entered into the Web-based EpiCom database, www.ecco-epicom.eu. RESULTS: A total of 711 adult patients were diagnosed during the inclusion year 2011, 178 (25%) from Eastern, 461 (65%) from Western Europe and 72 (10%) from Australia; 259 (37%) patients were diagnosed with Crohn's disease, 380 (53%) with ulcerative colitis and 72 (10%) with IBD unclassified. The mean annual incidence rate for IBD was 11.3/100,000 in Eastern Europe, 14.0/100,000 in Western Europe and 30.3/100,000 in Australia. Significantly more patients were diagnosed with complicated disease at diagnosis in Eastern Europe compared to Western Europe (43% vs. 27%, p=0.02). CONCLUSION: Incidence rates, disease phenotype and initial treatment characteristics in the 2011 ECCO-EpiCom cohort were not significantly different from that reported in the 2010 cohort.

Associations between functional polymorphisms in the NFκB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease.

Antitumor necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. Genetic markers may predict individual response to anti-TNF therapy. Using a candidate gene approach, 39 mainly functional single nucleotide polymorphisms (SNPs) in 26 genes regulating inflammation were assessed in 738 prior anti-TNF-naive Danish patients with IBD. The results were analyzed using logistic regression (crude and adjusted for age, gender and smoking status). Nineteen functional polymorphisms that alter the NFκB-mediated inflammatory response (TLR2 (rs3804099, rs11938228, rs1816702, rs4696480), TLR4 (rs5030728, rs1554973), TLR9 (rs187084, rs352139), LY96 (MD-2) (rs11465996), CD14 (rs2569190), MAP3K14 (NIK) (rs7222094)), TNF-α signaling (TNFA (TNF-α) (rs361525), TNFRSF1A (TNFR1) (rs4149570), TNFAIP3(A20) (rs6927172)) and other cytokines regulated by NFκB (IL1B (rs4848306), IL1RN (rs4251961), IL6 (rs10499563), IL17A (rs2275913), IFNG (rs2430561)) were associated with response to anti-TNF therapy among patients with CD, UC or both CD and UC (P ⩽ 0.05). In conclusion, the results suggest that polymorphisms in genes involved in activating NFκB through the Toll-like receptor (TLR) pathways, genes regulating TNF-α signaling and cytokines regulated by NFκB are important predictors for the response to anti-TNF therapy among patients with IBD. Genetically strong TNF-mediated inflammatory response was associated with beneficial response. In addition, the cytokines IL-1ß, IL-6 and IFN-γ may be potential targets for treating patients with IBD who do not respond to anti-TNF therapy. These findings should be examined in independent cohorts before these results are applied in a clinical setting.

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. Crohn's 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.

Health care and patients' education in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom study.

BACKGROUND AND AIMS: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD). METHODS: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers. RESULTS: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88% p=0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p<0.05). CONCLUSION: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.

East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort.

OBJECTIVE: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East-West gradient in the incidence of IBD in Europe exists. DESIGN: A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. RESULTS: 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100,000 in 2010 for CD were 6.5 (range 0-10.7) in Western European centres and 3.1 (range 0.4-11.5) in Eastern European centres, for UC 10.8 (range 2.9-31.5) and 4.1 (range 2.4-10.3), respectively, and for IBDU 1.9 (range 0-39.4) and 0 (range 0-1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. CONCLUSIONS: An East-West gradient in IBD incidence exists in Europe. Among this inception cohort--including indolent and aggressive cases--international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. METHODS: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. RESULTS: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01). CONCLUSIONS: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.