http://repub.eur.nl/res/aut/16930/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39180/ 2012-06-06T00:00:00Z No one would argue that men and women differ. The differences between the sexes are obvious and affect every aspect of life. The biological grounds for these differences are determined by the complementary yet distinct roles of the two sexes in the process of procreation. The success of human reproduction is related to the very efficient selection process for the proper genetic material that will, after 40 weeks of intense physical investment by the female, result in the birth of a healthy progenitor1. This ultimate goal of procreation determines the basic differences between male and female biology that presumably functions at the level of every cell. http://repub.eur.nl/res/pub/31956/ 2012-01-01T00:00:00Z A 62-year-old man with alcoholic liver cirrhosis underwent liver transplantation. The transplantation went uneventful and the ultrasound imaging of the liver performed after transplantation did not show any abnormalities. Eighteen months later, an intra-hepatic focal lesion was found on ultrasound. A contrast-enhanced ultrasound revealed a lesion with a malignant pattern of contrast uptake. The histo-pathological and subsequent molecular-pathological analysis concluded a colorectal metastasis of donor origin. The donor had no history of malignancy but no complete autopsy had been performed which illustrates the importance of the meticulous donors' screening. Transplanted patients carry a high risk of developing malignancy in general but donor related-tumors are very rare. The therapeutic considerations differ substantially between recipient- and donor-related malignancies. Therefore, considering the possibility of donor-related tumor by raising suspicion of malignant lesion with appropriate imaging and distinction from recipient-related malignancy by molecular analysis are crucial for proper therapeutic decision. http://repub.eur.nl/res/pub/34599/ 2011-12-01T00:00:00Z Background: Although new therapeutic strategies have been developed to control Crohn's disease, medical treatment for refractory cases is not able to prevent extensive and/or repeat surgery. Recently, several cases have been reported of successful remission induction in Crohn's disease patients by means of hematopoietic stem cell transplantation (HSCT). Here we report our long-term (4 to 6. years) outcome in three patients. Patients: Three patients (two male, one female) with active severe Crohn's disease were planned to undergo autologous HSCT. All patients were intolerant or refractory to conventional therapies, including anti-TNFα antibodies. Patients either refused surgery or surgery was considered not to be a feasible alternative due to the extensive disease involvement of the small intestine. Methods: Peripheral blood stem cells were mobilized using a single infusion of cyclophosphamide 4g/m2, followed on day 4 by subcutaneous injections with G-CSF 5μg/kg twice daily until leukapheresis. CD34+ cells were isolated after leukapheresis by magnetic cell sorting. In two of the three patients a second round of stem cell mobilization using G-CSF only was required, either because of low yield or because of insufficient recovery after CD34 selection. Prior to transplantation, immune ablation was achieved using cyclophosphamide 50mg/kg/day (4days), antithymocyte globulin 30mg/kg/day (3days) and prednisolone 500mg (3days). Endoscopy, barium small bowel enteroclysis and MRI enterography were performed. Results: All three patients successfully completed stem cell mobilization, and two of them subsequently underwent conditioning and autologous HSCT with CD34+ cell selection. Treatment was well tolerated, with acceptable toxicity. Now, 5 and 6. years post-transplantation, these patients are in remission under treatment. The third patient went into remission after mobilization and therefore she decided not to undergo conditioning and HSCT transplantation. After a successful pregnancy she relapsed two years later. Since then, she suffers from refractory Crohn's disease for which we are now reconsidering conditioning and transplantation. Conclusion: Autologous HSCT appears to be safe and can be an alternative strategy for Crohn's disease patients with severe and therapy resistant disease. http://repub.eur.nl/res/pub/25932/ 2011-05-01T00:00:00Z Aliment Pharmacol Ther 2011; 33: 1053-1058 Summary Background Typically, inflammatory bowel disease (IBD) patients are in their reproductive years, raising questions about safely using antitumour necrosis factor antibodies like infliximab (IFX) during pregnancy. IgG antibodies naturally cross the placenta, especially during the last trimester. To prevent foetal intra-uterine exposure, stopping IFX treatment at gestational week 30 is recommended. However, whether this limits intra-uterine and early postnatal IFX exposure is unestablished. Aim To determine the intra-uterine exposure to IFX following maternal treatment with IFX. Methods Four pregnant IBD patients intentionally continued IFX during pregnancy. IFX levels were assessed in newborns' cord blood and the mothers' peripheral blood at delivery. The children's development during the first 3-6 months, infections, vaccine reactions and antibody responses to vaccinations against Haemophilus influenzae type b and Pneumococcus were assessed. Results The patients stopped IFX therapy at gestational week 21, 26, 26 and 30, respectively. In three infants, therapeutic IFX levels were present in cord blood at levels of 5.5-13.7 Îg/mL and were two- to three-fold higher than in the peripheral blood of their mothers. During the 3- to 6-month follow-up, the children developed normally without signs of infections or allergic reactions, and had normal antibody titres after routine childhood vaccinations. Conclusion The use of IFX until gestational week 30 leads to foetal intra-uterine exposure to IFX at levels that exceed those in the mothers' peripheral blood. Although no short-term complications were detected, the high IFX levels observed in newborns raise concerns about unknown effects of IFX on the developing immune system. http://repub.eur.nl/res/pub/27612/ 2010-04-14T00:00:00Z Objective. It is estimated that 10%30% of Crohn's disease (CD) patients have small-bowel lesions, but the exact frequency and clinical relevance of these findings are unknown. Double-balloon enteroscopy (DBE) enables endoscopic visualization of the small bowel. The aim of this study was to evaluate the use of DBE for detecting small-bowel lesions in CD patients suspected of having small-bowel involvement. Furthermore, the clinical impact of adjusting treatment in these patients was assessed. Material and methods. A prospective study was performed in a tertiary referral center. CD patients suspected of small-bowel involvement and in whom distal activity had previously been excluded were included. All patients underwent DBE, followed by step-up therapy in patients with small-bowel lesions. The presence of small-bowel lesions during DBE was noted and clinical outcome was assessed after adjusting therapy. Results. Thirty-five patients (70%) showed small-bowel lesions; these lesions could not be assessed by conventional endoscopy in 23 (46%). At 1-year follow-up, step-up therapy in 26 patients (74%) led to clinical remission in 23 (88%). This was confirmed by a significant decrease in Crohn's disease activity index and mucosal repair on second DBE. Conclusions. DBE showed a high frequency of small-bowel lesions in known CD patients with clinically suspected small-bowel activity. Most of these lesions were not accessible for conventional endoscopy. Adjusting treatment in patients with small-bowel CD involvement led to clinical remission and mucosal repair in the majority of cases. http://repub.eur.nl/res/pub/27336/ 2010-01-06T00:00:00Z Objective. Inflammatory bowel disease (IBD) affects patients in reproductive age but little is known about the peri-conceptional use of medication for IBD. The aim of this study was to assess the type of medication used by IBD patients with the desire to reproduce and changes in medication in the peri-conceptional period. Material and methods. IBD patients with active conception plans and pregnant patients were prospectively recruited from the outpatient clinic of a single academic medical center. IBD-related medication and changes in this medication for reasons of a desire to conceive or pregnancy were analyzed. Results. In total, 61 patients (51 females; 40 with Crohn's disease, 21 with ulcerative colitis) were included. Thirteen patients (21%) used no medication, 44 (72%) used monotherapy and four (7%) used combination treatment. Of patients on monotherapy, 11 (19%) used 5-aminosalicylates, five (9%) used steroids, 11 (19%) used thiopurines, five (9%) used methotrexate and 11 (19%) used anti-tumor necrosis factor agents. Thirty-seven patients (61%) consulted a physician prior to conception. About one-third of these patients required a change in their medication due to their conception plans. Conclusions. In a referral center, the majority of IBD patients with conception plans require medication for which limited information on the safety of peri-conceptional use is available. In addition, the desire to reproduce leads to medication changes in about one-third of these patients. http://repub.eur.nl/res/pub/24752/ 2009-10-01T00:00:00Z SummaryBackground Adherence is important for successful treatment in inflammatory bowel disease (IBD) patients. Previous studies demonstrated high prevalence of non-adherence. Aim To assess IBD-patients' perceptions of therapy adherence and disease-related functional status in members of the Dutch patients' association of Crohn's disease and ulcerative colitis (CCUVN). Methods Inflammatory bowel disease-patients completed anonymously a survey at the website of the CCUVN. Statistical analysis was performed using principal component analysis, univariate and multivariate logistic regression. Results The questionnaire was completed by 1067 patients [617 (58%) Crohn's disease (CD) and 450 (42%) ulcerative colitis (UC)]. Mean age was 43 years (s.d. 13.7); women (66%). Of 920 patients currently using medication, 797 (87%) were adherent. Of the patients using 5-ASA, 91% were adherent (527/582), vs. 96% using corticosteroids (316/330) and 97% (414/425) using immunosuppressives. CD patients (OR 1.54; 95% CI 1.05-2.27), patients with duration of disease ≤8 years (OR 2.25; 95% CI 1.49-3.39) were more adherent. Fifty percent of patients reported a low functional status and were limited in daily activities. Conclusion This population-based study shows high therapy adherence, but low functional status in Dutch CCUVN-related IBD-patients. The high adherence rate in this present study could be an effect of CCUVN membership. http://repub.eur.nl/res/pub/27164/ 2009-07-01T00:00:00Z http://repub.eur.nl/res/pub/14589/ 2008-11-01T00:00:00Z 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.