Dynamic contrast-enhanced MRI in patients with luminal Crohn's disease.

OBJECTIVES: To prospectively assess dynamic contrast-enhanced (DCE-)MRI as compared to conventional sequences in patients with luminal Crohn's disease. METHODS: Patients with Crohn's disease undergoing MRI and ileocolonoscopy within 1 month had DCE-MRI (3T) during intravenous contrast injection of gadobutrol, single shot fast spin echo sequence and 3D T1-weighted spoiled gradient echo sequence, a dynamic coronal 3D T1-weighted fast spoiled gradient were performed before and after gadobutrol. Maximum enhancement (ME) and initial slope of increase (ISI) were calculated for four colon segments (ascending colon+coecum, transverse colon, descending colon+sigmoid, rectum) and (neo)terminal ileum. C-reactive protein (CRP), Crohn's disease activity index (CDAI), per patient and per segment Crohn's disease endoscopic index of severity (CDEIS) and disease duration were determined. Mean values of the (DCE-)MRI parameters in each segment from each patient were compared between four disease activity groups (normal mucosa, non-ulcerative lesions, mild ulcerative and severe ulcerative disease) with Mann-Whitney test with Bonferroni adjustment. Spearman correlation coefficients were calculated for continuous variables. RESULTS: Thirty-three patients were included (mean age 37 years; 23 females, median CDEIS 4.4). ME and ISI correlated weakly with segmental CDEIS (r=0.485 and r=0.206) and ME per patient correlated moderately with CDEIS (r=0.551). ME was significantly higher in segments with mild (0.378) or severe (0.388) ulcerative disease compared to normal mucosa (0.304) (p<0.001). No ulcerations were identified at conventional sequences. ME correlated with disease duration in diseased segments (r=0.492), not with CDAI and CRP. CONCLUSIONS: DCE-MRI can be used as a method for detecting Crohn's disease ulcerative lesions.

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

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.

Anti tumour necrosis factor as risk factor for free perforations in Crohn's disease? A case-control study.

AIM: Although the occurrence of intestinal perforation in Crohn's disease (CD) is rare, clinical observation has led to the question whether anti tumour necrosis factor (TNF) treatment is a risk factor for free perforation. The aim of this study was to investigate the possible relation between anti-TNF treatment and occurrence of free perforation, defined as intestinal perforations leading to emergency surgery. METHOD: In this case-control study, all emergency operation reports from the period 1999-2009 of patients diagnosed with CD were checked for the presence of free perforation. These cases were compared with a sixfold larger control group derived from our CD patient database. Cases and controls were matched for age, gender, Montreal classification and surgical stage to ensure equal disease severity. Cases and controls were then compared regarding previous or current exposure to anti-TNF treatment. RESULTS: Thirteen patients underwent emergency surgery for spontaneous free perforation. Eight (62%) had been treated with anti-TNF within 5 months before the perforation. In the 78 matched controls, 29 (37%) had been or were still treated with anti-TNF. The odds for a free perforation adjusted for known confounders in two separate regression analyses were significantly higher in anti-TNF treated CD patients, albeit with a large confidence interval (OR 4.1, 95% CI: 1.1-16.0; and OR 23.0, 95% CI 2.2-238.5). CONCLUSION: This study showed a higher occurrence of free perforations in CD patients with anti-TNF therapy compared with those without anti-TNF therapy. Patients with CD and anti-TNF treatment showing acute abdominal pain must be suspected of this complication.

Pilot study of probe-based confocal laser endomicroscopy during colonoscopic surveillance of patients with longstanding ulcerative colitis.

BACKGROUND AND AIMS: Surveillance of patients with ulcerative colitis consists of taking targeted and random biopsies, which is time-consuming and of doubtful efficiency. The use of probe-based confocal laser endomicroscopy (pCLE) may increase efficiency. This prospective pilot study aimed to evaluate the feasibility and diagnostic accuracy of pCLE in ulcerative colitis surveillance. METHODS: In 22 patients with ulcerative colitis, 48 visible lesions and 87 random areas were initially evaluated by real-time narrow-band imaging (NBI) and high-definition endoscopy (HDE). Before taking biopsies, fluorescein-enhanced pCLE was performed. All pCLE videos were scored afterwards by two endoscopists who were blinded to histology and endoscopy. Outcome measures were: (1) the feasibility of pCLE, expressed as pCLE imaging time required, percentage of imaging time with clear pCLE histology, and pCLE video quality as rated by two endoscopists; and (2) the diagnostic accuracy of pCLE. RESULTS: The median pCLE imaging time required was 98 seconds for lesions vs. 66 seconds for random areas ( P = 0.002). The median percentages of imaging time with clear pCLE histology were 61 % vs. 81 % respectively ( P < 0.001). The pCLE video quality was rated as good/excellent in 69 %. Feasibility was significantly poorer for sessile and pedunculated mobile lesions. The sensitivity, specificity, and accuracy of blinded pCLE were 65 %, 82 %, and 81 %, whereas these figures were 100 %, 89 %, and 92 % for real-time endoscopic diagnosis with NBI and HDE. CONCLUSION: This study demonstrates that pCLE for ulcerative colitis surveillance is feasible with reasonable diagnostic accuracy. Future research should show whether increased experience with pCLE improves its ease of use and whether real-time pCLE diagnosis is associated with greater diagnostic accuracy.

Narrow-band imaging versus high-definition endoscopy for the diagnosis of neoplasia in ulcerative colitis.

BACKGROUND AND STUDY AIMS: Controversy exists about which colonoscopic technique is most sensitive for the diagnosis of neoplasia in patients with ulcerative colitis. We compared new-generation narrow-band imaging (NBI) to high-definition endoscopy (HDE) for the detection of neoplasia and evaluated NBI for the differentiation of neoplastic from non-neoplastic mucosa. PATIENTS AND METHODS: Randomized crossover trial in which patients with ulcerative colitis underwent both NBI and HDE colonoscopy in random order with at least 3 weeks between the two procedures, which were performed by different endoscopists. Lesions detected during the first examination were left in situ in order to enable detection during the second examination as well. Main outcome measures were (1) neoplasia detection, and (2) diagnostic accuracy of NBI for differentiating neoplastic from non-neoplastic mucosa by using the Kudo classification and vascular pattern intensity (VPI). RESULTS: Twenty-five patients were randomized to undergo HDE first and 23 to undergo NBI first. Of 16 neoplastic lesions, 11 (69 %) were detected by HDE and 13 (81 %) by NBI ( P = 0.727). Of 11 patients with neoplasia, 9 (82 %) were diagnosed by HDE and 8 (73 %) by NBI ( P = 1.0). The sensitivity, specificity, and accuracy of the Kudo classification were 76 %, 66 % and 67 %. Corresponding figures for VPI were 80 %, 72 %, and 73 %. CONCLUSION: NBI does not improve the detection of neoplasia in patients with ulcerative colitis compared to HDE. In addition, NBI proves unsatisfactory for differentiating neoplastic from non-neoplastic mucosa.

Suicide attempt in ulcerative colitis patient after 4 months of infliximab therapy--a case report.

In the summary of product characteristics of infliximab (IFX), psychiatric side effects are reported to be rare, and in literature only limited data exist. This report presents a case of a patient with ulcerative colitis who developed a depression with psychotic symptoms during IFX therapy and made a suicide attempt 4 months after the initiation of therapy. Although the time between start of IFX therapy and onset of symptoms could suggest a correlation, this, of course, does not prove that IFX was the causative factor for his depression and suicide attempt.

Laparoscopic resection with transcolonic specimen extraction for ileocaecal Crohn's disease.

BACKGROUND: Ileocolic resection for Crohn's disease can be performed entirely laparoscopically. However, an incision is needed for specimen extraction. This prospective observational study assessed the feasibility of endoscopic transcolonic specimen removal. METHODS: Endoscopic specimen removal was attempted in a consecutive series of ten patients scheduled for laparoscopic ileocolic resection. Primary outcomes were feasibility, operating time, reoperation rate, pain scores, morphine requirement and hospital stay. To assess applicability, outcomes were compared with previous data from patients who had laparoscopically assisted operations. RESULTS: Transcolonic removal was successful in eight of ten patients; it was considered not feasible in two patients because the inflammatory mass was too large (7-8 cm). Median operating time was 208 min and median postoperative hospital stay was 5 days. After surgery two patients developed an intra-abdominal abscess, drained laparoscopically or percutaneously, and one patient had another site-specific infection. The operation took longer than conventional laparoscopy, with no benefits perceived by patients in terms of cosmesis or body image. CONCLUSION: Transcolonic removal of the specimen in ileocolic Crohn's disease is feasible in the absence of a large inflammatory mass but infection may be a problem. It is unclear whether the technique offers benefit compared with conventional laparoscopic surgery.

Long-term outcomes following laparoscopically assisted versus open ileocolic resection for Crohn's disease.

BACKGROUND: Long-term results of laparoscopically assisted versus open ileocolic resection for Crohn's disease were evaluated in a randomized trial. METHODS: Sixty patients who underwent ileocolic resection between 1999 and 2003 were followed prospectively. Primary outcomes were reoperation, readmission and repeat resection rates for recurrent Crohn's disease. Secondary outcomes were quality of life (QOL), body image and cosmesis. RESULTS: Five patients were lost to follow-up. Median follow-up was 6.7 (interquartile range 5.7-7.9) years. Sixteen of 29 and 16 of 26 patients remained relapse free after ileocolic resection in the laparoscopic and open groups respectively (risk difference 6 (95 per cent confidence interval - 20 to 32) per cent). Resection of recurrent Crohn's disease was necessary in two of 29 versus three of 26 patients (risk difference 5 (-11 to 20) per cent). Overall reoperation rates for recurrent Crohn's disease, incisional hernia and adhesion-related problems were two of 29 versus six of 26 (risk difference 16 (-3 to 35) per cent). QOL was similar, whereas body image and cosmesis scores were significantly higher after laparoscopy (P = 0.029 and P < 0.001 respectively). CONCLUSION: Laparoscopically assisted ileocolic resection results in better body image and cosmesis, whereas open surgery is more likely to produce incisional hernia and obstruction.

Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel disease.

BACKGROUND: Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse. METHOD: The aim of this study was to compare tumour stage and survival of IBD patients with CRC who were a part of a surveillance programme with those who were not. A nationwide pathology database (PALGA (pathologisch anatomisch landelijk geautomatiseerd archief)) was consulted to identify IBD patients with CRC treated in all eight university hospitals in The Netherlands over a period of 15 years. Patients were assigned to the surveillance group when they had undergone one or more surveillance colonoscopies before a diagnosis of CRC. Patients who had not undergone surveillance served as controls. Tumour stage and survival were compared between the two groups. RESULTS: A total of 149 patients with IBD-associated CRC were identified. Twenty-three had had colonoscopic surveillance before CRC was discovered. The 5-year CRC-related survival rate of patients in the surveillance group was 100% compared with 74% in the non-surveillance group (P=0.042). In the surveillance group, only one patient died as a consequence of CRC compared with 29 patients in the control group (P=0.047). In addition, more early tumour stages were found in the surveillance group (P=0.004). CONCLUSIONS: These results provide evidence for improved survival from colonoscopic surveillance in IBD patients by detecting CRC at a more favourable tumour stage.

Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis.

OBJECTIVES: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and psoriasis), while the roles that interleukin 2 (IL2) and IL21 play in the immune response also make them attractive candidates for IBD. The objective of this study was to test for association between the IL2/IL21 locus and the IBDs. METHODS: The four single nucleotide polymorphisms (SNPs) in the IL2/IL21 locus most associated with coeliac disease were genotyped in 1590 subjects with IBD and 929 controls from The Netherlands, and then replicated in a North American cohort (2387 cases and 1266 controls) and an Italian cohort (805 cases and 421 controls), yielding a total of 4782 cases (3194 UC, 1588 CD) and 2616 controls. Allelic association testing and a pooled analysis using a Cochran-Mantel-Haenszel test were performed. RESULTS: All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35 x 10(-10), rs13119723 p = 8.60 x 10(-8), rs6840978 p = 3.0 7x 10(-8), rs6822844 p = 2.77 x 10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86 x 10(-5)). CONCLUSIONS: A strong association for the IL2/IL21 locus with UC was found, which also confirms it as a general susceptibility locus for inflammatory disease.

More right-sided IBD-associated colorectal cancer in patients with primary sclerosing cholangitis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) and concurrent primary sclerosing cholangitis (PSC) have a higher risk of developing colorectal cancer (CRC) than IBD patients without PSC. The aim of this study was to investigate potential clinical differences between patients with CRC in IBD and those with CRC in IBD and PSC, as this may lead to improved knowledge of underlying pathophysiological mechanisms of CRC development. METHODS: The retrospective study from 1980-2006 involved 7 Dutch university medical centers. Clinical data were retrieved from cases identified using the national pathology database (PALGA). RESULTS: In total, 27 IBD-CRC patients with PSC (70% male) and 127 IBD-CRC patients without PSC (59% male) were included. CRC-related mortality was not different between groups (30% versus 19%, P = 0.32); however, survival for cases with PSC after diagnosing CRC was lower (5-year survival: 40% versus 75% P = 0.001). Right-sided tumors were more prevalent in the PSC group (67% versus 36%, P = 0.006); adjusted for age, sex, and extent of IBD, this difference remained significant (odds ratio: 4.8, 95% confidence interval [CI] 2.0-11.8). In addition, tumors in individuals with PSC were significantly more advanced. CONCLUSIONS: The right colon is the predilection site for development of colonic malignancies in patients with PSC and IBD. When such patients are diagnosed with cancer they tend to have more advanced tumors than patients with IBD without concurrent PSC, and the overall prognosis is worse. Furthermore, the higher frequency of right-sided tumors in patients with PSC suggests a different pathogenesis between patients with PSC and IBD and those with IBD alone.

Molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort.

BACKGROUND: Crohn's disease and ulcerative colitis have a complex genetic background. We assessed the risk for both the development and severity of the disease by combining information from genetic variants associated with inflammatory bowel disease (IBD). METHODS: We studied 2804 patients (1684 with Crohn's disease and 1120 with ulcerative colitis) and 1350 controls from seven university hospitals. Details of the phenotype were available for 1600 patients with Crohn's disease and for 800 with ulcerative colitis. Genetic association for disease susceptibility was tested for the nucleotide-binding and oligomerisation domain 2 gene (NOD2), the IBD5 locus, the Drosophila discs large homologue 5 and autophagy-related 16-like 1 genes (DLG5 and ATG16L1) and the interleukin 23 receptor gene (IL23R). Interaction analysis was performed for Crohn's disease using the most associated single nucleotide polymorphism (SNP) for each locus. Odds ratios were calculated in an ordinal regression analysis with the number of risk alleles as an independent variable to analyse disease development and severity. RESULTS: Association with Crohn's disease was confirmed for NOD2, IBD5, DLG5, ATG16L1 and IL23R. Patients with Crohn's disease carry more risk alleles than controls (p = 3.85 x 10(-22)). Individuals carrying an increasing number of risk alleles have an increasing risk for Crohn's disease, consistent with an independent effects multiplicative model (trend analysis p = 4.25 x 10(-23)). Patients with Crohn's disease with a more severe disease course, operations or an age of onset below 40 years have more risk alleles compared to non-stricturing, non-penetrating behaviour (p = 0.0008), no operations (p = 0.02) or age of onset above 40 years (p = 0.028). CONCLUSION: Crohn's disease is a multigenic disorder. An increase in the number of risk alleles is associated with an increased risk for the development of Crohn's disease and with a more severe disease course. Combining information from the known common risk polymorphisms may enable clinicians to predict the course of Crohn's disease.

Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn's disease.

BACKGROUND: Adalimumab is an effective treatment in patients with Crohn's disease; as it is a humanized anti-tumour necrosis factor monoclonal antibody, immunogenicity is thought not to be of any significance. AIM: To assess whether antibodies to adalimumab (ATAs) affect adalimumab treatment outcome in patients with Crohn's disease previously treated with infliximab. METHODS: A retrospective study was performed. Patients with active Crohn's disease and who had lost response or were intolerant to infliximab were treated with adalimumab. Clinical response and side effects were assessed as were serum ATAs and antibodies to infliximab (ATIs). RESULTS: In total 30 patients [M/F (7/23)], median age 36 years (range 21-73) were treated with adalimumab for 318 days (median range 83-632). Clinical response was 77% (23/30), a dose escalation was necessary in eight (27%) patients and side effects were observed in 47% (14/30). In five patients (17%) ATAs were detected; of these patients, four were nonresponders. The presence of ATAs was related to nonresponse to adalimumab (P = 0.006). ATIs were positive in 57% of patients (17/30) and serum levels were significantly increased in adalimumab nonresponders (P = 0.01). CONCLUSION: Immunogenicity plays a role in adalimumab treatment because of the development of ATAs.

Endoscopic tri-modal imaging for surveillance in ulcerative colitis: randomised comparison of high-resolution endoscopy and autofluorescence imaging for neoplasia detection; and evaluation of narrow-band imaging for classification of lesions.

BACKGROUND: Endoscopic tri-modal imaging (ETMI) incorporates white light endoscopy (WLE), autofluorescence imaging (AFI) and narrow-band imaging (NBI). AIMS: To assess the value of ETMI for the detection and classification of neoplasia in patients with longstanding ulcerative colitis. DESIGN: Randomised comparative trial of tandem colonoscopies. SETTING: Academic Medical Centre Amsterdam, Netherlands. PATIENTS AND METHODS: Fifty patients with ulcerative colitis underwent surveillance colonoscopy with ETMI. Each colonic segment was inspected twice, once with AFI and once with WLE, in random order. All detected lesions were inspected by NBI for Kudo pit pattern analysis and additional random biopsies were taken. MAIN OUTCOME MEASURES: Neoplasia miss-rates of AFI and WLE, and accuracy of the Kudo classification by NBI. RESULTS: Among patients assigned to inspection with AFI first (n = 25), 10 neoplastic lesions were primarily detected. Subsequent WLE detected no additional neoplasia. Among patients examined with WLE first (n = 25), three neoplastic lesions were detected; subsequent inspection with AFI added three neoplastic lesions. Neoplasia miss-rates for AFI and WLE were 0% and 50% (p = 0.036). The Kudo classification by NBI had a sensitivity and specificity of 75% and 81%; however, all neoplasia was coloured purple on AFI (sensitivity 100%). No additional patients with neoplasia were detected by random biopsies. CONCLUSION: Autofluorescence imaging improves the detection of neoplasia in patients with ulcerative colitis and decreases the yield of random biopsies. Pit pattern analysis by NBI has a moderate accuracy for the prediction of histology, whereas AFI colour appears valuable in excluding the presence of neoplasia. TRIAL REGISTRATION NUMBER: ISRCTN05272746.

High frequency of early colorectal cancer in inflammatory bowel disease.

BACKGROUND AND AIMS: To detect precancerous dysplasia or asymptomatic cancer, patients suffering from inflammatory bowel disease often undergo colonoscopic surveillance based on American or British guidelines. It is recommended that surveillance is initiated after 8-10 years of extensive colitis, or after 15-20 years for left-sided disease. These starting points, however, are not based on solid scientific evidence. Our aim was to assess the time interval between onset of inflammatory bowel disease (IBD) and colorectal carcinoma (CRC), and subsequently evaluate how many patients developed cancer before their surveillance was recommended to commence. METHODS: A nationwide automated pathology database (PALGA) was consulted to identify patients with IBD-associated colorectal carcinoma in seven university medical centres in The Netherlands between January 1990 and June 2006. Data were collected retrospectively from patient charts. Time intervals between onset of disease and cancer diagnosis were calculated in months. RESULTS: 149 patients were identified with confirmed diagnoses of IBD and CRC (ulcerative colitis n = 89/Crohn's disease n = 59/indeterminate colitis n = 1). Taking date of diagnosis as the entry point, 22% of patients developed cancer before the 8 or 15 year starting points of surveillance, and 28% if surveillance was commenced 10 or 20 years after diagnosis for extensive or left-sided disease, respectively. Using onset of symptoms to calculate the time interval, 17-22% of patients would present with cancer prior to the surveillance starting points. CONCLUSIONS: These results show that the diagnosis of colorectal cancer is delayed or missed in a substantial number of patients (17-28%) when conducting surveillance strictly according to formal guidelines.

Pharmacogenetics of thiopurine therapy in paediatric IBD patients.

BACKGROUND: Azathioprine is widely used in the treatment of children with inflammatory bowel disease. The occurrence and type of adverse events to azathioprine may be related to thiopurine S-methyltransferase (TPMT) enzyme activity and to inosine triphophate pyrophosphatase (ITPase) deficiency. AIM: Investigate frequencies of functional TPMT polymorphisms and ITPA polymorphisms and their association with the occurrence of adverse events during azathioprine therapy in a paediatric inflammatory bowel disease population. METHODS: Seventy-two azathioprine treated paediatric inflammatory bowel disease patients, 47% girls, mean age 12.5 years (range 6.5-17.5), were assessed for TPMT and ITPA polymorphisms and for adverse events. The relation between polymorphisms and adverse events is evaluated. RESULTS: Of all azathioprine treated patients, 11 experienced an adverse event for which azathioprine was stopped: pancreatitis (n = 4), leucopenia (n = 2) and 'general malaise' (n = 5). Of the 11 patients who stopped azathioprine because of adverse events, 10 had wild-type alleles for all investigated genotypes. Genotyping of ITPA 94C>A polymorphisms showed that two patients were homozygous, both tolerated azathioprine well. CONCLUSIONS: No association of functional ITPA and TPMT polymorphisms and the occurrence of azathioprine related adverse events could be detected. Pharmacogenetic assessment prior to thiopurine therapy does not seem warranted.

New cytokine therapeutics for inflammatory bowel disease.

Conventional therapy for inflammatory bowel diseases rely on corticosteroids and 5-aminosalicylates combined with immunosuppressive agents for maintenance. These drugs are not always effective and may inflict serious side effects. Other therapies are therefore awaited. Infliximab, a monoclonal antibody against the pro-inflammatory cytokine TNF-alpha has been successfully applied as a treatment for Crohn's disease. The mechanism of action of this drug extends beyond the level of TNF-alpha scavenging and includes induction of apoptosis of effector cells. Numerous anti-TNF antibodies have been developed and are currently evaluated in clinical trials. Other targets for monoclonal antibodies include integrins and cytokines involved in T-cell differentiation and activation. Likewise recombinant proteins that moderate TNF bioactivity and lymphocyte function have been developed. The therapeutic effect of recombinant interleukin-10 seems to be dependent on local delivery of the protein. Antisense therapy targeting lymphocyte migration has also been tested in IBD. Finally, the conventional drug thalidomide and possibly MAP-kinase inhibitors may become novel treatment entities for IBD.