C.J. van der Woude

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.

High frequency of early colorectal cancer in inflammatory bowel disease

Background and aim: 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.

Clinical and endosonographic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn's disease with infliximab: A double-blind placebo-controlled study

Background : Ciprofloxacin is effective in perianal Crohns disease but after treatment discontinuation symptoms reoccur. Infliximab is effective but requires maintenance therapy.

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 × 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 × 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.

High intra-uterine exposure to infliximab following maternal anti-TNF treatment during pregnancy

Aliment Pharmacol Ther 2011; 33: 1053–1058

Review article: defining remission in ulcerative colitis

Aliment Pharmacol Ther 2011; 34: 113–124

Hidradenitis suppurativa and inflammatory bowel disease: are they associated? Results of a pilot study.

Background  The co‐occurrence of hidradenitis suppurativa (HS) and Crohn disease (CD) published in a few case reports resulted in the wide acceptance of an association between these two diseases. However, the combined prevalence of these diseases is currently unknown; furthermore, it is unknown whether this co‐occurrence also applies for ulcerative colitis (UC).

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.

Chronic inflammation, apoptosis and (pre-)malignant lesions in the gastro-intestinal tract

Inflammatory conditions are characterized by activation of the transcription factor nuclear factor kappa B (NF-κB), resulting in the expression of NF-κB-regulated, inflammation-related genes, such as inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2). Expression of these genes contributes to the survival of cells. Indeed, exposure to pro-inflammatory cytokines in the absence of NF-κB activation leads to apoptosis.1,2 Chronic inflammatory conditions are accompanied by constitutive activation of NF-κB and hence, to the continuous expression of pro-survival genes, as has been observed in chronic gastritis.3 Although beneficial for the survival of cells during exposure to inflammatory stress, the continuous activation of NF-κB may also pose a risk: cells with a pro-survival phenotype may give rise to continuously proliferating cells and may thus be tumorigenic. Progression to a malignant phenotype of these cells will most likely involve additional changes in the expression of non-NF-κB regulated genes e.g. a shift in the balance of pro- and anti-apoptotic genes towards a more anti-apoptotic phenotype. Literature on inflammation-related genes and the apoptotic balance in pre-malignant and malignant conditions in the gastro-intestinal tract is still scarce and conflicting. In this review, we aim to give an overview of the existing literature and we will focus on inflammation- and apoptosis-related genes in the sequence of normal epithelium-inflamed epithelium-metaplasia-dysplasia-cancer in the gastrointestinal tract, in particular esophagus (Barretts esophagus: BE), stomach (gastritis) and colon (inflammatory bowel disease: IBD).

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. (Inflamm Bowel Dis 2009)