Guidelines for the management of Helicobacter pylori infection in Italy: The III Working Group Consensus Report 2015.

Knowledge on the role of Helicobacter pylori (HP) infection is continually evolving, and treatment is becoming more challenging due to increasing bacterial resistance. Since the management of HP infection is changing, an update of the national Italian guidelines delivered in 2007 was needed. In the III Working Group Consensus Report 2015, a panel of 17 experts from several Italian regions reviewed current evidence on different topics relating to HP infection. Four working groups examined the following topics: (1) "open questions" on HP diagnosis and treatment (focusing on dyspepsia, gastro-oesophageal reflux disease, non-steroidal anti-inflammatory drugs or aspirin use and extra-gastric diseases); (2) non-invasive and invasive diagnostic tests; (3) treatment of HP infection; (4) role of HP in the prevention of gastric cancer. Statements and recommendations were discussed and a consensus reached in a final plenary session held in February 2015 in Bologna. Recommendations are based on the best current evidence to help physicians manage HP infection in Italy. The guidelines have been endorsed by the Italian Society of Gastroenterology and the Italian Society of Digestive Endoscopy.

Extraintestinal manifestations in Crohn's disease and ulcerative colitis: results from a prospective, population-based European inception cohort.

BACKGROUND: In chronic inflammatory bowel disease (IBD) (Crohn's disease [CD] and ulcerative colitis [UC]), symptoms from outside the gastrointestinal tract are frequently seen, and the joints, skin, eyes, and hepatobiliary area are the most usually affected sites (called extraintestinal manifestations [EIM]). The reported prevalence varies, explained by difference in study design and populations under investigation. The aim of our study was to determine the prevalence of EIM in a population-based inception cohort in Europe and Israel. METHODS: IBD patients were incepted into a cohort that was prospectively followed from 1991 to 2004. A total of 1145 patients were followed for 10 years. RESULTS: The cumulative prevalence of first EIM was 16.9% (193/1145 patients) over a median follow-up time of 10.1 years. Patients with CD were more likely than UC patients to have immune-mediated (arthritis, eye, skin, and liver) manifestations: 20.1% versus 10.4% (p < 0.001). Most frequently seen was arthritis which was significantly more common in CD (12.9%) than in UC (8.1%), p = 0.01. Pan-colitis compared to proctitis in UC increased the risk of EIM. CONCLUSION: In a European inception cohort, EIMs in IBD were consistent with that seen in comparable studies. Patients with CD are twice as likely as UC patients to experience EIM, and more extensive distribution of inflammation in UC increases the risk of EIM.

Isolated colorectal cancer screening or integrated cancer prevention? A provocative suggestion!

Colorectal cancer (CRC) screening is still not fully established in the European Union. Recently, the United European Gastroenterology Federation (UEGF) supported CRC screening with the publication of quality guidelines and a written declaration in the European Parliament in favor of European-wide monitored CRC screening and primary prevention of CRC, the latter particularly in young citizens. In this article, the need for population-based CRC screening is once again stressed. In addition, the value of opportunistic CRC screening is pointed out, either as a regional or nation-wide alternative (such as in the USA and Germany) or as a 'forerunner' activity in view of subsequent population-based CRC screening. With regard to other parallel organ-related screening activities in Europe (breast, uterus) and the increasing need for primary prevention of malignant and benign diseases, the question is raised as to whether preventive activities should not be recognized as an integrated and logical part of a 'healthcare chain' offered to all European citizens.

New European initiatives in colorectal cancer screening: Budapest Declaration. Official appeal during the Hungarian Presidency of the Council of the European Union under the Auspices of the United European Gastroenterology Federation, the European Association for Gastroenterology and Endoscopy and the Hungarian Society of Gastroenterology.

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associated deaths can be avoided through early detection by high-quality colorectal screening programs followed by appropriate treatment. Under the auspices of the United European Gastroenterology Federation (UEGF), the European Association for Gastroenterology and Endoscopy, the Hungarian Society of Gastroenterology and the Hungarian College of Gastroenterology, the 'Budapest Declaration' (2011) was an accepted official scientific program during the Hungarian Presidency of the Council of the European Union. The Budapest Declaration follows the Munich Declaration (2001), the Brussels Declaration (2007), the Transatlantic Declaration (2009), the Barcelona Declaration (2010), the written declaration of CRC screening, a joint initiative with European Parliamentarians coordinated by the UEGF, and finally, the 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis'. The 'Budapest Declaration' together with previous declarations aims to urge the national and supranational healthcare decision makers to launch new Europe-wide initiatives to establish high-quality CRC programs to achieve optimal efficiency in CRC screening. In case of implementation of the proposals, actions and conditions recommended, we can achieve that one of the basic principles of the EU - the chance of equal access - be realized in member states with respect to the prevention of CRC and reduction of cancer-related mortality. To better achieve this goal, we propose to establish an UEGF joint committee, with one participant representing each EU member state to coordinate and supervise the implementation of CRC screening.

Cancer in inflammatory bowel disease 15 years after diagnosis in a population-based European Collaborative follow-up study.

AIM OF THE STUDY: To determine the occurrence of intestinal and extraintestinal cancers in the 1993-2009 prospective European Collaborative Inflammatory Bowel Disease (EC-IBD) Study Group cohort. PATIENTS-METHODS: A physician per patient form was completed for 681 inflammatory bowel disease patients (445UC/236CD) from 9 centers (7 countries) derived from the original EC-IBD cohort. For the 15-year follow up period, rates of detection of intestinal and extraintestinal cancers were computed. RESULTS: Patient follow-up time was fifteen years. In total 62/681 patients (9.1%) [41 with ulcerative colitis/21 with Crohn's disease, 36 males/26 females] were diagnosed with sixty-six cancers (four patients with double cancers). Colorectal cancer was diagnosed in 9/681 patients [1.3%] (1 Crohn's disease and 8 ulcerative colitis). The remaining 53 cancers were extraintestinal. There was a higher prevalence of intestinal cancer in the Northern centers compared to Southern centers [p=NS]. Southern centers had more cases of extraintestinal cancer compared to Northern centers [p=NS]. The frequency of all observed types of cancers in Northern and in Southern centers did not differ compared to the expected one in the background population. CONCLUSIONS: In the fifteen-year follow up of the EC-IBD Study Group cohort the prevalence of cancer was 9.1% with most patients having a single neoplasm and an extraintestinal neoplasm. In Northern centers there were more intestinal cancers while in Southern centers there were more extraintestinal cancers compared to Northern centers. In this IBD cohort the frequency of observed cancers was not different from that expected in the background population.

Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas.

Given the current increase in colorectal cancer screening, information on performance of screening tests is needed, especially in groups with a presumed lower test performance. We compared test performance of immunologic fecal occult blood testing (FIT) and pseudosigmoidoscopy with colonoscopy for detection of advanced adenomas in an average risk screening population. In addition, we explored the influence of gender, age, and location on test performance. FIT was collected prior to colonoscopy with a 50 ng/mL cutoff point. FIT results and complete colonoscopy findings were available from 329 subjects (mean age: 54.6 ± 3.7 years, 58.4% women). Advanced adenomas were detected in 38 (11.6%) of 329 subjects. Sensitivity for advanced adenomas of FIT and sigmoidoscopy were 15.8% (95% CI: 6.0-31.3) and 73.7% (95% CI: 56.9-86.6), respectively. No sensitivity improvement was obtained using the combination of sigmoidoscopy and FIT. Mean fecal hemoglobin in FIT positives was significantly lower for participants with only proximal adenomas versus those with distal ones (P = 0.008), for women versus men (P = 0.023), and for younger (<55 years) versus older (≥55 years) subjects (P = 0.029). Sensitivities of FIT were 0.0% (95% CI: 0.0-30.9) in subjects with only proximal versus 21.4% (95% CI: 8.3-41.0) in those with distal nonadvanced adenomas; 5.3% (95% CI: 0.0-26.0) in women versus 26.3% (95% CI: 9.2-51.2) in men; 9.5% (95% CI: 1.2-30.4) in younger versus 23.5% (95% CI: 6.8-49.9) in older subjects. Sigmoidoscopy had a significantly higher sensitivity for advanced adenomas than FIT. A single FIT showed very low sensitivity, especially in subjects with only proximal nonadvanced adenomas, in women, and in younger subjects. This points to the existence of "low" FIT performance in subgroups and the need for more tailored screening strategies.

The first 2 years of colorectal cancer screening in Ferrara, Italy.

We report on the first screening round in the District of Ferrara, a region of Emilia-Romagna, carried out between March 2005 and March 2007 to illustrate the effort of colorectal cancer (CRC) screening from administration and information to therapy and follow-up. After invitation of 38 344 persons aged 50-69 years (28.5%), 19 480 (50.8%) accepted the immunological faecal occult blood test, with 1 149 (6%) resulting positive. One thousand and one individuals (88.2%) who tested positive for immunological faecal occult blood test accepted examination by either colonoscopy (99.5%) or barium enema (0.5%). Out of 996 screenees having a colonoscopy, 231 had low-risk adenomas (23.2%) and 239 had high-risk adenomas (24%), and were treated endoscopically (96%) or surgically (4%). Ninety-one cancers were diagnosed in 9.1% of colonoscopies (Dukes stadia: A, 58.2%; B, 19.8%; C, 18.7%; D, 3.3%). Fourteen cancers (all in polyps) were treated endoscopically, and the remaining 77 were treated by surgery. One Dukes B patient and 13 of 17 Dukes C patients received adjuvant chemotherapy. Three Dukes D patients had chemotherapy only. During the 2-year study period, 87 screenees had a follow-up colonoscopy: no neoplasia was found in 35 patients initially diagnosed with cancer; low-risk adenomas were found in 31 of 52 patients with initial high-risk adenomas. In conclusion, the first CRC screening round in Ferrara was easy to organize, had a high acceptance, and detected 91 cancers (78% of which were in Dukes stages A and B, compared with only 40% in sporadic CRC in the same background population). Chemotherapy was necessary in 17 cases. This report may motivate other health authorities to initiate CRC screening campaigns.

Screenee perception and health-related quality of life in colorectal cancer screening: a review.

Screening for colorectal cancer (CRC) has become established to varying degrees in several Western countries for the past 30 years. Because of its effectiveness, screening has been adopted or is planned in a number of other countries. In most countries, the screening method (e.g., fecal occult blood test [FOBT], sigmoidoscopy) is followed by colonoscopy, for verification. In other countries (e.g., United States, Germany), colonoscopy is the preferred first-line investigation method. However, because colonoscopy is considered to be invasive, might be poorly tolerated, and can be associated with complications, the idea of adopting colonoscopy as the primary screening method suffers. Negative effects of screening methods can reduce participation in programs and thereby negate the desired effect on individual and societal health. At present, there is no generally accepted method either to assess the perception and satisfaction of patients screened or the outcome of the screening procedures in CRC. In this review, we discuss the past development and present availability of instruments to measure health-related quality of life (HRQoL), the scarce studies in which such instruments have been used in screening campaigns, and the findings. We suggest the creation of a specific instrument for the assessment of HRQoL in CRC screening.

Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

OBJECTIVE: The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). MATERIAL AND METHODS: A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. RESULTS: Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. CONCLUSION: Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.

Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to Respond.

In the past four decades, chemoprevention of colorectal cancer (CRC) has been the subject of many epidemiologic and intervention trials of naturally occurring or pharmacologic agents. Recently, the positioning of cyclooxygenase 2 inhibitors as a viable option in this context was a major breakthrough; however, it was hampered by adverse cardiovascular events. This review questions whether chemopreventive measures for CRC are ready to be used in mass or individual applications, standing alone or in combination with other CRC-preventive measures. It also discusses steps that may be undertaken to explore this field further.

Mortality in inflammatory bowel disease in the Netherlands 1991-2002: results of a population-based study: the IBD South-Limburg cohort.

BACKGROUND: The aim was to evaluate overall and disease-specific mortality in a population-based inflammatory bowel disease (IBD) cohort in the Netherlands, as well as risk factors for mortality. METHODS: IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. Standardized mortality ratios (SMRs) were calculated overall and with regard to causes of death, gender, as well as age, phenotype, smoking status at diagnosis, and medication use. RESULTS: At the censoring date, 72 out of 1187 patients had died (21 Crohn's disease [CD], 47 ulcerative colitis [UC], and 4 indeterminate colitis [IC] patients). The SMR (95% confidence interval [CI]) was 1.1 (0.7-1.6) for CD, 0.9 (0.7-1.2) for UC and 0.7 (0.2-1.7) for IC. Disease-specific mortality risk was significantly increased for gastrointestinal (GI) causes of death both in CD (SMR 7.5, 95% CI: 2.8-16.4) and UC (SMR 3.4, 95% CI: 1.4-7.0); in CD patients, especially in patients <40 years of age at diagnosis. For UC, an increased SMR was noted in female patients and in patients <19 years and >80 years at diagnosis. In contrast, UC patients had a decreased mortality risk from cancer (SMR 0.5, 95% CI; 0.2-0.9). CONCLUSIONS: In this population-based IBD study, mortality in CD, UC, and IC was comparable to the background population. The increased mortality risk for GI causes might reflect complicated disease course, with young and elderly patients at diagnosis needing intensive follow-up. Caution in interpreting the finding on mortality risk from cancer is needed as follow-up was probably to short to observe IBD-related cancers.

Methylation of TFPI2 in stool DNA: a potential novel biomarker for the detection of colorectal cancer.

We have used a gene expression array-based strategy to identify the methylation of tissue factor pathway inhibitor 2 (TFPI2), a potential tumor suppressor gene, as a frequent event in human colorectal cancers (CRC). TFPI2 belongs to the recently described group of embryonic cell Polycomb group (PcG)-marked genes that may be predisposed to aberrant DNA methylation in early stages of colorectal carcinogenesis. Aberrant methylation of TFPI2 was detected in almost all CRC adenomas (97%, n = 56) and stages I to IV CRCs (99%, n = 115). We further explored the potential of TFPI2 as a biomarker for the early detection of CRC using stool DNA-based assays in patients with nonmetastatic CRC and average-risk noncancer controls who were candidates for screening. TFPI2 methylation was detected in stool DNA from stage I to III CRC patients with a sensitivity of 76% to 89% and a specificity of 79% to 93%. Detection of TFPI2 methylation in stool DNA may act as a useful adjunct to the noninvasive strategies for screening of CRCs in the future.

Appropriate management of special situations in Crohn's disease (upper gastro-intestinal; extra-intestinal manifestations; drug safety during pregnancy and breastfeeding): Results of a multidisciplinary international expert panel-EPACT II.

INTRODUCTION: High-grade evidence is lacking for most therapeutic decisions in Crohn's disease. Appropriateness criteria were developed for upper gastro-intestinal, extra-intestinal manifestations and drug safety during conception, pregnancy and breastfeeding in patients with Crohn's disease, to assist the physician in clinical decision making. METHODS: The European Panel on the Appropriateness of Crohn's Disease Therapy (EPACT II), a multidisciplinary international European expert panel, rated clinical scenarios based on evidence from the published literature and panelists' own clinical expertise. Median ratings (on a 9-point scale) were stratified into three categories: appropriate (7-9), uncertain (4-6 with or without disagreement) and inappropriate (1-3). Experts were also asked to rank appropriate medications by priority. RESULTS: Proton pump inhibitors, steroids, azathioprine/6-mercaptopurine and infliximab are appropriate for upper gastro-duodenal Crohn's disease; for stenosis, endoscopic balloon dilation is the first-line therapy, although surgery is also appropriate. Ursodeoxycholic acid is the only appropriate treatment for primary sclerosing cholangitis. Infliximab is appropriate for Pyoderma gangrenosum, ankylosing spondylitis and uveitis, steroids for Pyoderma gangrenosum and ankylosing spondylitis, adalimumab for Pyoderma gangrenosum and ankylosing spondylitis, cyclosporine-A/tacrolimus for Pyoderma gangrenosum. Mesalamine, sulfasalazine, prednisone, azathioprine/6-mercaptopurine, ciprofloxacin, and probiotics, may be administered safely during pregnancy or for patients wishing to conceive, with the exception that male patients considering conception should avoid sulfasalazine. Metronidazol is considered safe in the 2nd and 3rd trimesters whereas infliximab is rated safe in the 1st trimester but uncertain in the 2nd and 3rd trimesters. Methotrexate is always contraindicated at conception, during pregnancy or during breastfeeding, due to its known teratogenicity. Mesalamine, prednisone, probiotics and infliximab are considered safe during breastfeeding. CONCLUSION: EPACT II recommendations are freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation.

High prevalence of morphometric vertebral deformities in patients with inflammatory bowel disease.

BACKGROUND: Earlier studies have documented that the prevalence of decreased bone mineral density (BMD) is elevated in patients with inflammatory bowel disease. The objective of this study was to investigate the prevalence of vertebral deformities in inflammatory bowel disease patients and their relation with BMD and bone turnover. METHODS: One hundred and nine patients with Crohn's disease (CD) and 72 with ulcerative colitis (UC) (age 44.5+/-14.2 years) were studied. BMD of the hip (by dual X-ray absorptiometry) was measured and a lateral single energy densitometry of the spine for assessment of vertebral deformities was performed. Serum markers of bone resorption (carboxy-terminal cross-linked telopeptide of type I collagen) and formation (procollagen type I amino-terminal propeptide) were measured, and determinants of prevalent vertebral deformities were assessed using logistic regression analysis. RESULTS: Vertebral deformities were found in 25% of both CD and UC patients. Comparing patients with and without vertebral deformities, no significant difference was found between Z-scores and T-scores of BMD, or levels of serum carboxy-terminal cross-linked telopeptide of type I collagen and serum procollagen type I amino-terminal propeptide. Using logistic regression analysis the only determinant of any morphometric vertebral deformity was sex. The presence of multiple vertebral deformities was associated with older age and glucocorticoid use. CONCLUSION: The prevalence of morphometric vertebral deformities is high in CD and UC. Male sex, but neither disease activity, bone turnover markers, clinical risk factors, nor BMD predicted their presence. The determinants for having more than one vertebral deformity were age and glucocorticoid use. This implies that in addition to screening for low BMD, morphometric assessment of vertebral deformities is warranted in CD and UC.

Serological markers are associated with disease course in ulcerative colitis. A study in an unselected population-based cohort followed for 10 years.

OBJECTIVES: Perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) have been proposed as markers for diagnosis and for subtyping of inflammatory bowel disease (IBD). The aim of this study was to investigate the association of p-ANCA and ASCA with a 10-year disease outcome in terms of cumulative rate of colectomy and relapse in a population-based European inception cohort of ulcerative colitis (UC) patients. METHODS: Serum samples from 432 consenting patients were analysed for p-ANCA and ASCA. The results were compared with the cumulative colectomy rate, relapsing disease and total number of relapses. We used multiple regression analyses adjusted for age, sex, residence, disease extent at diagnosis, smoking, familial IBD and drug treatment to study the relationship between serological values and disease course. RESULTS: The relapse rate was higher in the p-ANCA-positive patients: 82% (95% confidence interval [CI] 75-89%) compared with 67% (CI 62-72%, p=0.011) in the p-ANCA-negative patients. The risk of relapsing disease course was higher by a factor of 1.4 (CI 1.1-1.8, p=0.009) for p-ANCA-positive patients than for p-ANCA-negative patients, and the corresponding relative risk (RR) for the total number of relapses was 1.9 (CI 1.7-2.1, p<0.001). In ASCA-positive patients RR for the total number of relapses was 1.8 (CI 1.5-2.1, p<0.001). No significant association with colectomy rate was found for the presence of either p-ANCA or ASCA. CONCLUSION: UC patients positive for p-ANCA and possibly for ASCA may have a more unfavourable long-term disease outcome in terms of relapse than UC patients without these markers.

Rectal nitric oxide and fecal calprotectin in inflammatory bowel disease.

OBJECTIVE: The assessment of intestinal inflammation in patients with inflammatory bowel disease (IBD) remains a difficult challenge. Both rectal nitric oxide (NO) and fecal calprotectin can be measured using non-invasive methods and are emerging as promising inflammatory markers in IBD. In this study the aim was to compare calprotectin and NO levels in IBD patients. MATERIAL AND METHODS: Rectal NO was measured tonometrically in 23 healthy volunteers and 32 patients with IBD. In addition, we collected stool samples from all subjects for measurement of fecal calprotectin and nitrate/nitrite (NO metabolites). RESULTS: Patients with IBD had greatly increased NO and calprotectin levels compared to healthy volunteers (p <0.001). In addition, the nitrate levels were slightly increased in IBD patients. A weak correlation was found between rectal NO levels, disease activity and number of loose stools in IBD patients (Spearman's rho 0.37 and 0.51, respectively; p <0.05). Fecal calprotectin correlated only with age (Spearman's rho 0.51; p <0.01). However, no correlation was found between NO and calprotectin. CONCLUSIONS: Both rectal NO and fecal calprotectin are greatly increased during bowel inflammation, but they may reflect different parts of the inflammatory process. Future studies will elucidate the clinical usefulness of these two markers.

Ulcerative colitis: patient characteristics may predict 10-yr disease recurrence in a European-wide population-based cohort.

OBJECTIVES: Cumulative 10-yr relapse rates in ulcerative colitis (UC) of 70% to almost 100% have been reported in regional studies. The aim of this study was to determine the relapse rate in UC in a European population-based cohort 10 yr after diagnosis and to identify factors that may influence the risk of relapse. METHODS: From 1991 to 1993, 771 patients with UC from seven European countries and Israel were prospectively included in a population-based inception cohort and followed for 10 yr. A relapse was defined as an increase in UC-related symptoms leading to changes in medical treatment or surgery. The cumulative relapse rate, time to first relapse, and number of relapses in the follow-up period were recorded and possible causative factors were investigated. RESULTS: The cumulative relapse rate of patients with at least one relapse was 0.67 (95% CI 0.63-0.71). The time to first relapse showed a greater hazard ratio (HR) (1.2, CI 1.0-1.5) for women and for patients with a high level of education (1.4, CI 1.1-1.8). The number of relapses decreased with age, and current smokers had a lower relapse rate (0.8, CI 0.6-0.9) than nonsmokers. The relapse rate in women was 1.2 (CI 1.1-1.3) times higher than in men. An inverse relation was found between the time to the first relapse and the total number of relapses. CONCLUSION: In 67% of patients, there was at least one relapse. Smoking status, level of education, and possibly female gender were found to influence the risk of relapse.

Treatment inferred disease severity in Crohn's disease: evidence for a European gradient of disease course.

OBJECTIVE: Geographic differences in disease course of Crohn's disease (CD) might possibly be related to differences in genetic and environmental factors encountered in different parts of the world. The aim of this study was to assess differences in treatment regimens within a European cohort of CD patients as a reflection of disease course, and to identify associated phenotypic risk factors at diagnosis. MATERIAL AND METHODS: A prospective European population-based inception cohort of 380 CD patients was studied. The patients were classified for phenotype according to the Vienna classification. Differences between Northern and Southern European centres in treatment over the first 10 years of disease were analysed using a competing risks survival analysis method. RESULTS: Patients in the North were more likely to have had surgery (p<0.01), whereas patients in the South were more likely to have been treated medically (p<0.01). Phenotype at diagnosis was not predictive of differences in treatment regimens between North and South. CONCLUSIONS: In this study, a difference in management of CD was observed between Northern and Southern European centres. This suggests that there may be a North-South disease severity gradient across Europe. Phenotypic differences between patients in the North and South did not explain this observed difference.

Role of ASCA and the NOD2/CARD15 mutation Gly908Arg in predicting increased surgical costs in Crohn's disease patients: a project of the European Collaborative Study Group on Inflammatory Bowel Disease.

BACKGROUND: NOD2/CARD15, the first identified susceptibility gene in Crohn's disease (CD), is associated with ileal stenosis and increased frequency of surgery. Anti-Saccharomyces cerevisiae antibody (ASCA), a serological marker for CD, is associated with ileal location and a high likelihood for surgery. We hypothesized that the presence of ASCA and NOD2/CARD15 mutations could predict increased health care cost in CD. METHODS: CD patients in a prospectively designed community-based multinational European and Israeli cohort (n = 228) followed for mean 8.3 (SD 2.6) years had blood drawn for measurement of ASCA (IgG, IgA), Arg702Trp, Gly908Arg, and Leu1007fsinsC. Days spent in the hospital and the costs of medical and surgical hospitalizations and medications were calculated. RESULTS: The median duration of surgical hospitalizations was longer in Gly908Arg-positive than -negative patients, 3.5 and 1.5 days/patient-year (P < 0.01), and in ASCA-positive than -negative patients, 1.1 and 0 days/patient-year (P < 0.001). Median surgical hospitalization cost was 1,580 euro/patient-year in Gly908Arg-positive versus 0 euro/patient-year in -negative patients (P < 0.01), and 663 euro/patient-year in ASCA-positive versus 0 euro/patient-year in -negative patients (P < 0.001). Differences in cost of medications between groups were not significant. The effect of Gly908Arg was expressed in countries with higher Gly908Arg carriage rates. ASCA raised surgical costs independently of the age at diagnosis of disease. Arg702Trp and Leu1007fsinsC did not affect the cost of health care. CONCLUSIONS: Since CD patients positive for Gly908Arg and ASCA demonstrated higher health care costs, it is possible that measurement of Gly908Arg and ASCA at disease diagnosis can forecast the expensive CD patients.