Journal of Crohn's and Colitis

Issue Contents list

2012-02-01

The effect of smoking on intestinal inflammation: What can be learned from animal models?

Stephanie Verschuere, Rebecca De Smet, Liesbeth Allais, Claude A. Cuvelier — 2011-10-13

Abstract: Epidemiological evidence demonstrates that smoking is the most important environmental risk factor in Crohn's disease while it positively interferes with the disease course of ulcerative colitis. However, the underlying mechanisms through which smoking exerts this divergent effect and affects pathogenesis of inflammatory bowel disease are largely unknown. Animal smoke models are good models to investigate the impact of cigarette smoke on intestinal physiology and inflammation. They enable one to explore the interaction of smoke components and the gut on cellular and molecular level, clarifying how smoking interferes with normal gut function and with disease course in inflammatory conditions. This review describes the currently used animal models for studying the impact of cigarette smoke on the intestinal tract. We first discuss the different methods for simulation of smoking. Furthermore, we focus on the effect of smoke exposure on normal gut physiology and immunology, on experimental (entero)colitis, and on inflammation-induced neoplasia. Based on this current knowledge, a hypothesis is formulated about the mechanisms through which cigarette smoke interferes with the gut in normal and pathological conditions.

Activated thrombin activatable fibrinolysis inhibitor (TAFIa) is associated with inflammatory markers in inflammatory bowel diseases: TAFIa level in patients with IBD

2011-07-15

Abstract: Background: Thrombin activatable fibrinolysis inhibitor (TAFI) has been reported to be involved in the pathogenesis and progression of inflammatory bowel disease (IBD). Activated TAFI (TAFIa) attenuates fibrinolysis by cleaving C-terminal lysine residues thus down-regulating plasminogen activation. To date, no reports on TAFIa in IBD have been published.Methods: Plasma levels of TAFIa were measured using a functional assay in 55 consecutive patients with ulcerative colitis (UC) and 50 with Crohn's disease (CD). Associations of TAFIa with disease activity, hemostatic variables and inflammatory markers were assessed.Results: Plasma TAFIa was higher in CD patients than in those with UC. The disease activity correlated positively with TAFIa levels in the UC group, but not in the CD group. In UC patients, there were positive correlations of TAFIa with white blood cells, C-reactive protein and fibrinogen and an inverse correlation with albumin. In the CD group, a positive correlation was shown for C-reactive protein, fibrinogen and platelet count, while a negative correlation was noted for albumin.Conclusions: This study is the first to show that TAFIa is increased in CD patients compared with UC and its levels are associated with inflammatory markers in both forms of IBD. These findings fit in the hypothesis that TAFIa may be a marker of active IBD, and in particular of active UC.Highlights: ► Thrombin activatable fibrinolysis inhibitor (TAFI) has been reported to be involved in the pathogenesis and progression of inflammatory bowel disease. ► This study is the first to show that TAFIa is increased in CD patients compared with UC and its levels are associated with inflammatory markers in both forms of IBD. ► TAFIa may be considered as a marker of exacerbated UC, but not CD.

Predictors for subsequent need for immunosuppressive therapy in early Crohn's disease

2011-07-18

Abstract: Background and aims: The clinical course of Crohn's disease (CD) is highly variable with a subgroup of patients developing a progressive disease course necessitating immunosuppressive therapy (IT). However, reliable, stable and non-invasive individual clinical parameters in order to identify patients at risk for undergoing subsequent IT have not been sufficiently established. We therefore aimed to identify such clinical parameters.Methods: A retrospective, multicenter analysis of CD patients from 6 German tertiary IBD centers was performed. Patients were classified into two groups depending on requiring IT or not. Personal data, clinical and laboratory parameters during the first 3months after CD diagnosis and effects of initial medical therapy were compared between these two groups.Results: In 218 (61.8%) of the 353 patients the CD course necessitated IT. Those patients were significantly younger at symptom onset and diagnosis, and required significantly more often a systemic corticosteroid therapy. Furthermore, significant differences in serological markers of inflammation were observed. Age, gender and the effect of initial steroid therapy were used to develop a prognostic model predicting the individual probability of necessitating IT.Conclusions: The simple clinical items age at diagnosis, gender, and need for systemic steroid therapy can predict a progressive disease course in early CD. Our model based on these parameters allows an individualized estimation of each patient's risk to develop a progressive disease course. Thereby, our model can help in deciding if patients will need immunosuppressive drugs early in the disease course or if a careful watch and wait strategy is justified.Highlights: ► Retrospective analysis from 6 German tertiary IBD centers involving 353 patients. ► Age, gender and effect of steroids are associated with necessity of immunosuppressors. ► A prognostic model predicts the patient's risk for a progressive disease course.

Risk factors in German twins with inflammatory bowel disease: Results of a questionnaire-based survey

2011-08-19

Abstract: Introduction: Environmental factors may play an important role in the pathogenesis of IBD. The history of patients of the German IBD twin study was analyzed by questionnaires and interviews.Methods: Randomly selected German monozygotic (MZ) and dizygotic (DZ) twins with at least one sibling suffering from IBD (n=512) were characterized in detail including demography, medical history and concomitant medications. Controls comprised of non-twin IBD patients (n=392) and healthy subjects (n=207).Results: The most significant variables that were associated with Crohn's disease (CD) or ulcerative colitis (UC) included living abroad before time of diagnosis (OR, 4.32; 95% CI, 1.57–13.69), high frequency of antibiotic use (MZ CD OR, 5.03; 95% CI 1.61–17.74, DZ CD OR, 7.66; 95% CI, 3.63–16.82, MZ UC OR, 3.82; 95% CI, 1.45–10.56, DZ UC OR, 3.08; CI, 1.63–5.92), high consumption of processed meat including sausage (MZ CD OR, 7.9; 95% CI, 2.15–38.12, DZ CD OR, 10.75; 95% CI, 4.82–25.55, MZ UC OR, 5.69; 95% CI, 1.89–19.48, DZ UC OR, 18.11; 95% CI, 7.34–50.85), and recall of bacterial gastrointestinal infections (MZ CD OR, 15.9; 95% CI, 4.33–77.14, DZ CD OR, 17.21; 95% CI, 4.47–112.5, MZ UC OR, 5.87; 95% CI, 1.61–28.0, DZ UC OR, 11.34; 95% CI, 4.81–29.67).Conclusions: This study reinforced the association of life style events, in particular a specific dietary and infections history, with IBD. Alteration of gut flora or alterations of the mucosal immune system in reactivity to the flora could be an important factor to explain the relationship between life-style and disease.

Genetic variants in autophagy-related genes and granuloma formation in a cohort of surgically treated Crohn's disease patients

2011-07-15

Abstract: Background and aims: Granulomas are a characteristic microscopic finding in Crohn's disease. Their clinical significance is controversial and their pathogenesis is unknown, but impaired processing of bacterial components has been suggested. Autophagy is a fundamental process involved in the elimination of intracellular bacteria. Genetic variants in autophagy genes IRGM and ATG16L1 have been associated with susceptibility to Crohn's disease. We therefore investigated whether variants in autophagy genes contribute to granuloma formation.Methods: Surgical specimens from 464 clinically well-documented Crohn's patients were reviewed and scored for the presence and distribution of granulomas. All patients were genotyped for the CD-associated SNPs in ATG16L1 and IRGM as well as for 77 haplotype tagging SNPs in 13 additional autophagy genes.Results: Granulomas were found in 75% of the patients. Their frequency increased with more distal involvement of the GI tract. Granuloma positive patients were significantly younger at the time of diagnosis and surgery, and were more likely to smoke. We identified associations between granulomas and autophagy gene variants ATG4A (rs5973822), FNBP1L (rs17109951) and ATG4D (rs7248026; rs2304165; rs10439163).Conclusion: These findings suggest that granuloma formation is a marker of a more aggressive disease course, and that variants in autophagy genes ATG4A, ATG2A, FNBP1L and ATG4D, may contribute to granuloma formation.Highlights: ► Granulomas are a marker of aggressive clinical behavior. ► Young patients develop granulomas more frequently with more granulomas in the bowel wall. ► Smokers are more likely to develop granulomas. ► Autophagy genes ATG4A, FNBP1L and ATG4D are associated with granuloma formation.

Upper gastrointestinal involvement in paediatric onset Crohn's disease: Prevalence and clinical implications

S. Crocco, S. Martelossi, N. Giurici, V. Villanacci, A. Ventura — 2011-08-01

Abstract: Background and aims: Our study evaluated the prevalence, the characteristics and implications of the upper gastrointestinal localisation (UGI+) in paediatric Crohn's Disease (CD) patients.Methods: This prospective study evaluated 45 newly diagnosed CD patients at diagnosis and follow up with respect to CD localisation.Results: All patients presented CD at the colon and/or ileum. In 24/45 patients (53.3%, 12 F and 12 M) an UGI+ involvement was also found. UGI+ patients had a younger age of onset (10.9years versus 12.6years; P<0.05). PCDAI at diagnosis was significantly higher in the UGI+ (41 vs. 25 P<0.01). UGI+ patients were overall more symptomatic. Pancolitis and extraintestinal manifestations were also more frequent (19/24 (80%) vs. 12/21 (57%) P<0.01). Growth was more impaired at diagnosis in UGI+ patients. By the end of the follow-up (mean 3years, range 2 to 4) no significant difference was found in PCDAI (17 in UGI+ patients vs. 11 in UGI− P=NS), or the number of relapses. Weight and growth catch-up in UGI+ patients were comparable to UGI− ones. However, UGI+ patients required a more aggressive therapeutic approach.Conclusion: At least half of paediatric onset CD patients have an upper gastrointestinal localisation. UGI+ patients present an earlier onset and a more severe disease. The final outcome does not differ, but UGI+ patients require a more aggressive therapeutic approach.Highlights: ► We evaluated the upper gastrointestinal localization in paediatric Crohn’s Disease (CD)patients. ► At least half of paediatric onset CD patients have an upper gastrointestinal localization. ► Patients with upper involvement present an earlier onset and a more severe disease. ► The final outcome does not differ , but patients with upper involvement require more aggressive therapy.

Recombinant human erythropoietin in patients with inflammatory bowel disease and refractory anemia: A 15-year single center experience

2011-08-18

Abstract: Aim of the study: To describe our 15-year experience on the patients' response and safety to the use of EPO in IBD patients with refractory anemia.Patients–Methods: Single center retrospective chart analysis of all IBD patients receiving EPO for the period 1994–2009. Patients with resistant anemia not responding to I.V. iron therapy were enrolled. Concommitant medication, medical and laboratory data on short and long-term patients' responses and safety were recorded.Results: In total 820 IBD files were reviewed and among 78 patients treated with I.V. iron we identified 26 patients who received EPO in concordance to our inclusion criteria. Azathioprine or methotrexate was administered in 17 patients and 7 patients received concomitant Infliximab. After EPO, 22/26 patients (84.6%) responded and peripheral blood parameters were significantly improved and blood transfusions were significantly decreased (p<0.001). Erythropoietin dose was increased in three non-responders while two patients required emergency transfusions. No adverse events were recorded.Conclusions: In anemic IBD patients who are refractory to I.V. iron monotherapy, administration of EPO significantly improved peripheral blood parameters with safety. Prospective controlled trials are needed to confirm positive patients' response to EPO and identify those patients who are more likely to benefit.

Intensification of infliximab therapy in Crohn's disease: Efficacy and safety

2011-08-22

Abstract: Introduction: The response of Crohn's disease (CD) to infliximab is initially good, although a loss of efficacy is observed over time. Dose escalation has been recommended in such cases.Aims: To study the response to an intensified infliximab regimen in patients with CD; and to evaluate the adverse effects associated with intensification of therapy and identify predictors of loss of response.Methods: We performed a retrospective multicenter survey of all patients with CD who had been treated with at least the 3 induction doses of standard infliximab therapy, and for whom treatment had to be intensified due to loss of response. We analyzed the efficacy of the intensified regimen.Results: Thirty-three patients were included. After the first intensification dose, 79% of patients had a clinical response (33.5% complete response, 45.5% partial response). In the long term, 83%, 69%, 47%, and 29% of patients who had an initial response to the intensification maintained the response at 6, 12, 18, and 36months, respectively. The loss of efficacy after escalation was 43% per patient-year of follow-up. One patient had an infusion reaction after 36 doses. One patient developed a herpes zoster infection.Conclusions: A high proportion of patients whose dose of infliximab is increased due to loss of efficacy respond initially. However, nearly half lose the response after one year. The safety profile of an intensified infliximab regimen is good.

Do Inflammatory Bowel Disease patients with anxiety and depressive symptoms receive the care they need?

2011-09-12

Abstract: Background and aims: Inflammatory Bowel Disease (IBD) patients with anxiety and/or depressive symptoms may not receive the care they need. Provision of care requires insight into the factors affecting these psychiatric symptoms. The study was designed to examine the extent to which: (1) IBD patients with anxiety and/or depressive symptoms receive mental treatment and (2) clinical and socio-demographic variables are associated with these symptoms.Methods: 231 adult IBD patients (79% response rate), attending a tertiary care center, completed standardized measures on anxiety and depressive symptoms (HADS), quality of life (SF-12) and mental health care use (TIC-P). Diagnosis and disease activity were determined by the gastroenterologist.Results: 43% had high levels of anxiety and/or depressive symptoms, indicative of a psychiatric disorder (HADS≥8), of whom 18% received psychological treatment and 21% used psychotropic medication. In multivariate analysis, high disease activity was associated with anxiety (OR=2.72 | p<0.03) and depression (OR=3.36 | p<0.01), while Crohn's disease was associated with anxiety (OR=2.60 | p<0.03).Conclusions: Despite high levels of anxiety and depressive symptoms and poor quality of life, psychiatric complaints in IBD patients were undertreated. Screening for and treatment of psychiatric symptoms should become an integral part of IBD medical care.Highlights: ► 18 % of IBD patients with high levels of anxiety and depression receive mental help. ► Higher levels of depression and anxiety are associated with having active disease. ► Screening should become an integral part of IBD medical care. ► Psychological interventions for anxiety and depression in IBD patients are needed.

Canadian cost-utility analysis of initiation and maintenance treatment with anti-TNF-α drugs for refractory Crohn's disease

2011-09-12

Abstract: Objectives: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Symptoms include but are not limited to abdominal pain, nausea, emesis, and diarrhea. Anti-TNF-α drugs are increasingly being used in patients with CD who have inadequate response to conventional therapy. However, these medications are quite expensive. The objective of this study is to evaluate the cost-utility of two anti-TNF-α drugs (infliximab, adalimumab) for refractory CD.Methods: A Markov model was used to estimate the costs and QALYs of three treatments (usual care, infliximab, adalimumab) over a 5year time horizon. After initial treatment, patients achieve remission, achieve treatment response or remain in the drug refractory health state. Patients who achieve remission or treatment response are at risk of relapse each 3month model cycle. Patients in the drug refractory health state either remain in the health state or have surgery in each cycle. Different costs and utility values were assigned to the various model health states. Model input parameters including initial response rates, relapse rates, utility values were derived from published literature.Results: Usual care had both the lowest expected costs ($17,017) and QALYs (2.555), while infliximab had both the highest expected costs ($54,084) and QALYs (2.721). The incremental cost per QALY moving from usual care to adalimumab and from adalimumab to infliximab was estimated to be to be $193,305 and $451,165, respectively.Conclusions: Based on common willingness to pay thresholds, ant-TNF-α drugs would not be perceived as a cost effective treatment for refractory CD.Highlights: ► We assess the cost-effectiveness of infliximab and adalimumab for chrohn’s disease. ► A 5 year probabilistic Markov model used. ► Adalimumab costs $193,305 per quality adjusted life year (QALY)versus to usual care. ► Infliximab costs $451,165 per QALY compared to adalimumab. ► Infliximab and adalimumabmay be poor value for money for Chron’s disease.

Diagnostic yield of upper endoscopy in paediatric patients with Crohn's disease and ulcerative colitis. Subanalysis of the HUPIR registry

2011-08-25

Abstract: Background, aims: According to Porto Criteria upper gastrointestinal (UGI) endoscopy is recommended in patients with suspected inflammatory bowel disease (IBD). Nevertheless, previous studies revealed frequent involvement of UGI tract even in patients with ulcerative colitis (UC). The aim of the present study was to determine the diagnostic role of esophagogastroduodenoscopy (EGD) and assess the prevalence and different aspects of UGI involvement in children registered in the Hungarian Pediatric IBD Registry (HUPIR) from 1st of January 2007 to 31th of December 2009.Methods: Twenty seven institutes provided prospective follow-up data about newly diagnosed IBD patients to HUPIR. The registry was based on detailed questionnaire (76 parameters) involving anamnestic data, laboratory findings, activity indexes, diagnostic procedures, endoscopic examinations (EGD and ileocolonoscopy), and histological data. Localization and phenotype of disease were based on the Montreal classification criteria.Results: During the 3-year period 420 children were diagnosed with IBD, 265 (63%) of them had Crohn's disease (CD), 130 (31%) UC, and 25 (6%) IBD-unclassified (IBD-U). The mean age at diagnosis was 13.2 years (range: 1.2–18 years). EGD was performed in 237 patients (56%), in most cases in patients suffering from CD. Macroscopic lesions on EGD were noted in 64% of patients with CD and 40% of children with UC. Characteristic lesions for CD (ulcer, erosion, aphthous lesion, and granuloma) were noted in 31% of CD patients, however, EGD helped to establish the final diagnosis in 9% of CD patients (diagnostic yield, 9%).Conclusions: There was a high frequency of UGI involvement in children with CD and UC. One third of CD patients showed significant lesions at upper endoscopy and one patient out of ten had real diagnostic help from EGD.Highlights: ► Upper gastrointestinal involvement is common in paediatric patients with IBD. ► Characteristic findings were noted in one third of patients with CD. ► Abnormalities observed in UC were unspecific and did not provide diagnostic help. ► EGD helped to establish the final diagnosis in 9% of CD patients (diagnostic yield).

Hepatotoxicity associated with 6-methyl mercaptopurine formation during azathioprine and 6-mercaptopurine therapy does not occur on the short-term during 6-thioguanine therapy in IBD treatment

2011-08-19

Abstract: Background and aims: High concentrations of methylated thiopurine metabolites, such as 6-methyl mercaptopurine, are associated with hepatotoxicity during administration of the conventional thiopurines azathioprine or 6-mercaptopurine in IBD patients. Metabolization of the non-conventional thiopurine 6-thioguanine does not generate 6-methyl mercaptopurine. Hence, the aim of our study was to evaluate hepatotoxicity during 6-thioguanine in IBD patients who previously failed conventional thiopurines due to 6-methyl mercaptopurine associated hepatotoxicity.Methods: A retrospective single center intercept cohort study was performed of IBD patients using 6-thioguanine between January 2006 and July 2010 after failing conventional thiopurine therapy due to 6-methyl mercaptopurine associated hepatotoxicity. The primary outcome was the occurrence of 6-thioguanine induced hepatotoxicity, scaled according to the Common Terminology Criteria for Adverse Events.Results: Nineteen patients were included. Median duration of 6-thioguanine therapy (median daily dosage 21mg (9–24)) was 23weeks (6–96). Hepatotoxicity did not reoccur in 15 out of 19, whereas grade 1 toxicity persisted in 4 patients (p<0.001). Median aspartate aminotransferase and alanine aminotransferase concentrations decreased from 34U/l (20–59) and 64U/l (15–175) to 23U/l (18–40; p=0.003) and 20U/l (14–48; p=0.019), respectively.Conclusion: Hepatotoxicity does not reoccur during 6-thioguanine treatment in most IBD patients who failed conventional thiopurines due to 6-methyl mercaptopurine associated hepatotoxicity. Hence, at least at short-term, 6-thioguanine appears a justifiable alternative thiopurine for these IBD patients.

Serum adenosine deaminase activity as a predictor of disease severity in ulcerative colitis

2011-08-19

Abstract: Background and aim: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by recurrent inflammation and ulcerations of colonic mucosa and an inappropriate and delayed healing. Adenosine deaminase (ADA) is a cytoplasmic enzyme involved in the catabolism of purine bases, capable of catalyzing the deamination of adenosine, forming inosine in the result process. Although ADA has been shown to increase in several inflammatory conditions, there are no literature data indicating an alteration in UC.Methods: This study evaluated the activity of total ADA in serum of 43 patients with UC and 18 healthy controls. Patients’ age, disease duration, drug intake, and other medical history were all noted for each subject. Complete blood count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were determined for both patients and controls. Correlation analysis was also performed between ADA and other inflammation markers of UC.Results: Serum mean ADA levels were 11.12±2.03 and 7.99±2.04 U/l for patients with UC in active state and in remission and 8.55±2.26 U/l in the healthy control group. Mean serum ADA levels were significantly elevated in active UC patients compared with patients with UC in remission and control groups. Overall accuracy of ADA in determination of active UC was 83.7 with sensitivity 83.3%, specificity 84.2%.Conclusions: Serum ADA levels were found to be elevated in UC patients in active state suggesting a partial role of activated T-cell response in the disease pathophysiology. Further randomized controlled studies are warranted to demonstrate the role of ADA in UC patients, with a special interest in specifically targeted therapies against ADA for achieving disease remission.

Acute and delayed hypersensitivity reactions to infliximab and adalimumab in a patient with Crohn's disease

2011-09-02

Abstract: A 61year old woman with active luminal Crohn's disease was successfully treated with infliximab induction therapy followed by 5 infusions every 8weeks. However, symptoms returned in the weeks preceding the 7th and 8th infusions. The 9th infusion was therefore given only 4weeks after the 8th infusion, but an acute severe anaphylactoid reaction occurred immediately after start of the infusion. Anti-infliximab IgG antibody concentration was high (100U/ml) prior to the 8th infusion and up to 1year after infliximab discontinuation (81U/ml). Anti-infliximab IgE antibodies were not found, and the anti-infliximab antibodies did not cross react with adalimumab. One week after the anaphylactoid reaction to infliximab, adalimumab therapy was initiated. Twelve days after the first adalimumab administration (80mg), a delayed hypersensitivity reaction occurred. This was likely caused by rapidly generated anti-adalimumab IgG antibodies (45U/ml), as these antibodies appeared to be specific for adalimumab in that infliximab failed to compete with adalimumab/anti-adalimumab antibody binding ex vivo. In conclusion, immunogenicity to infliximab and adalimumab may be associated with both acute anaphylactoid reactions and delayed hypersensitivity reactions. Reactions may be precipitated by newly induced specific anti-drug antibodies rather than by cross-reactivity of previously generated antibodies.

Colorectal small cell carcinoma in ulcerative colitis with identical rare p53 gene mutation to associated adenocarcinoma and dysplasia

2011-09-12

Abstract: Colorectal small cell carcinomas (SCCs) are rare tumors and are infrequently associated with ulcerative colitis (UC). We report a case of primary rectal SCC combined with adenocarcinoma arising in left-sided UC. Immunohistochemically, tumor cells were positive for chromogranin A, synaptophysin, and CD56 in the SCC but not in the adenocarcinoma. The patient simultaneously developed multiple lesions of adenocarcinoma and high-grade dysplasia in the sigmoid colon and rectum. To elucidate whether SCC might evolve from multipotential cells in dysplasia and/or adenocarcinoma, we examined the mutational status of TP53 and KRAS. The same clonality of these lesions including SCC was confirmed by the presence of an identical single nucleotide point mutation in TP53. KRAS mutation was not observed in these lesions. Thus, these lesions seem to have developed from the same origin. Long-standing inflammation leading to dysplasia might be responsible for the development of some SCCs in UC particularly when they are combined with dysplasia and/or adenocarcinoma.

Physician perspectives on unresolved issues in the use of conventional therapy in Crohn's disease: Results from an international survey and discussion programme

2011-10-20

Abstract: Background and aims: Data on the optimal use of conventional therapies in Crohn's disease are lacking in guidelines. An educational programme was established to explore questions raised in clinical practice and to provide practical answers.Methods: Telephone interviews with 96 gastroenterologists and a web survey of 1370 gastroenterologists identified 26 key questions. Ten questions were taken forward to the next stage based on the opinion of an International Steering Committee. Draft answers to the questions were prepared from available evidence following a literature search. The draft answers were debated in national meetings of participating countries (n=36) and voted on using a standard scoring system. Revised answers went forward to an international meeting and were debated and voted on using the same methodology. Final answers were developed, based on evidence and clinical experience of the participants.Results: Evidence on corticosteroid and immunomodulator use such as dosage, timing and duration, choice of drug or regimen, and safety is scarce. Key points of the answers included the importance of: identifying patients with poor prognosis; early intervention with optimal doses of immunomodulators; avoiding prolonged or repetitive corticosteroid therapy; achieving corticosteroid-free remission; achieving a balance between clinical benefit and safety when intensifying or prolonging therapy or combining different agents; re-evaluating therapy at appropriate time points; and considering the role of biomarkers and mucosal healing.Conclusions: The answers to 10 key questions were based on available evidence and clinical experience of programme participants. It is hoped they will be of practical use in everyday gastroenterology practice.

Erratum to “Cancer in inflammatory bowel disease 15years after diagnosis in a population-based European Collaborative follow-up study” [J Crohns Colitis (2011) 5, 430-442]

2012-02-01

The Publisher regrets that an error occurred in the last 4 lines of the Table (just before the references) of the EC-IBD centres and members. The correction is as follows:

Instruction for Authors

2012-02-01