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1. Risk Factors and Clinical Outcomes in Patients with IBD with Melanoma

Author

Nissen, Loes H. C., Pierik, Marieke, Derikx, Lauranne A. A. P., de Jong, Elke, Kievit, Wietske, van den Heuvel, Tim R. A., van Rosendael, Alexander R., Plasmeijer, Elsemieke I., Dewint, Pieter, Verhoeven, Rob H. A., Overbeek, Lucy I. H., Nagtegaal, Iris D., Hoentjen, Frank, and van der Meulen–de Jong, Andrea E.

Published
2017
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3. A 20-Year Temporal Change Analysis in Incidence, Presenting Phenotype and Mortality, in the Dutch IBDSL Cohort-Can Diagnostic Factors Explain the Increase in IBD Incidence?

Author

van den Heuvel, Tim R. A., van den Heuvel, Tim R. A., Jeuring, Steven F. G., Zeegers, Maurice P., van Dongen, Dorien H. E., Wolters, Anouk, Masclee, Ad A. M., Hameeteman, Wim H., Romberg-Camps, Marielle J. L., Oostenbrug, Liekele E., Pierik, Marieke J., Jonkers, Daisy M., van den Heuvel, Tim R. A., van den Heuvel, Tim R. A., Jeuring, Steven F. G., Zeegers, Maurice P., van Dongen, Dorien H. E., Wolters, Anouk, Masclee, Ad A. M., Hameeteman, Wim H., Romberg-Camps, Marielle J. L., Oostenbrug, Liekele E., Pierik, Marieke J., and Jonkers, Daisy M.

Abstract

Background: The aim was to study temporal changes in incidence, disease phenotype at diagnosis, and mortality of adult inflammatory bowel disease [IBD] patients in South Limburg, The Netherlands, diagnosed between 1991 and 2010. In addition, the 2010 IBD prevalence was estimated.Methods: A multi-faceted approach including hospital administrations, the national pathology registry [PALGA], and general practitioners led to the identification of 1162 patients with Crohn's disease [CD], 1663 with ulcerative colitis [UC], and 84 with unclassified IBD [IBD-U]. Temporal changes in incidence, disease phenotype, and mortality were studied using linear, multinomial regression analyses, and standardised mortality rates [SMR], respectively.Results: The annual incidences increased from 17.90/100000 in 1991 to 40.36/100000 in 2010 for IBD, from 5.84/100000 to 17.49/100000 for CD, and from 11.67/100000 to 21.47/100000 for UC p <0.01 for all]. A shift towards milder disease at diagnosis was observed over time [eg decrease of complicated disease in CD, increase of proctitis in UC]. IBD mortality was similar to that in the general population (SMR 0.92; 95% confidence interval [CI] 0.81-1.05), and did not change over time. The estimated IBD prevalence was 830/100000.Conclusions: The IBD incidence in South Limburg increased significantly between 1991 and 2010. The shift towards milder disease at diagnosis in parallel with the improved diagnostics and ability to detect low-grade inflammation was suggestive of an important role of diagnostic factors in this increase. Environmental factors probably played a role as well. The mortality was low and, together with the increasing incidence, led to the high prevalence of IBD in South Limburg.

Published
2017

4. Ambient air quality as risk factor for microscopic colitis - A geographic information system (GIS) study

Author

Verhaegh, Bas P. M., Verhaegh, Bas P. M., Bijnens, Esmee M., van den Heuvel, Tim R. A., Goudkade, Danny, Zeegers, Maurice P., Nawrot, Tim S., Masclee, Ad A. M., Jonkers, Daisy M. A. E., Pierik, Marieke J., Verhaegh, Bas P. M., Verhaegh, Bas P. M., Bijnens, Esmee M., van den Heuvel, Tim R. A., Goudkade, Danny, Zeegers, Maurice P., Nawrot, Tim S., Masclee, Ad A. M., Jonkers, Daisy M. A. E., and Pierik, Marieke J.

Abstract

Background: Microscopic colitis (MC) is considered a multifactorial disease, strongly associated with smoking. However, little is known about the role of environmental factors such as ambient air pollution in MC pathophysiology. There is an overlap in components of cigarette smoke and ambient air pollution. Therefore, the aim of this study was to explore an independent association between ambient air quality and MC.Methods: A case-control study was performed. MC cases in South Limburg, the Netherlands, diagnosed between 2000 and 2012, were retrieved from the national pathology registry and matched to non-MC controls from the same area based on age (+/- 2 years) and gender. A stable residential address for >= 3 years was required. Residential land use, proximity to major road, and concentrations of air pollution compounds, were determined using a Geographic Information System (GIS). Univariate and multivariable regression analyses were corrected for age, gender and smoking status.Results: In total, 345 MC cases (78.6% female) and 583 matched controls (77.2% female) were included. In the univariate analyses, the percentage of urban green within a 500 m buffer and residential proximity to the nearest highway were associated with MC (both p <0.10). On the multivariable level only a higher age at diagnosis (OR 1.02, 95%-CI 1.01-1.04) and current smoking at index date (OR 4.30; 95%-CI 3.01-6.14) were significantly associated with MC.Conclusion: Based on the current findings, ambient air quality does not seem to be an important risk factor for MC, in contrast to the well-known risk factors age and current smoking.

Published
2019

5. Development and Validation of a Patient-reported Score to Screen for Mucosal Inflammation in Inflammatory Bowel Disease

Author

de Jong, Marin J, primary, Roosen, Danielle, additional, Degens, Juliette H R J, additional, van den Heuvel, Tim R A, additional, Romberg-Camps, Marielle, additional, Hameeteman, W, additional, Bodelier, Alexander G L, additional, Romanko, Igor, additional, Lukas, Milan, additional, Winkens, Bjorn, additional, Markus, Tineke, additional, Masclee, Ad A M, additional, van Tubergen, Astrid, additional, Jonkers, Daisy M A E, additional, and Pierik, Marie J, additional

Published
2018
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6. Incidence and Classification of Postcolonoscopy Colorectal Cancers in Inflammatory Bowel Disease: A Dutch Population-Based Cohort Study

Author

Wintjens, Dion S J, primary, Bogie, Roel M M, additional, van den Heuvel, Tim R A, additional, le Clercq, Chantal M C, additional, Oostenbrug, Liekele E, additional, Romberg-Camps, Mariëlle J L, additional, Straathof, Jan-Willem, additional, Stassen, Laurents P S, additional, Masclee, Ad A M, additional, Jonkers, Daisy M A E, additional, Sanduleanu-Dascalescu, Silvia, additional, and Pierik, Marie J, additional

Published
2018
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7. Corticosteroid Sparing in Inflammatory Bowel Disease is More Often Achieved in the Immunomodulator and Biological Era—Results from the Dutch Population-Based IBDSL Cohort

Author

Jeuring, Steven F G, primary, Biemans, Vince B C, additional, van den Heuvel, Tim R A, additional, Zeegers, Maurice P, additional, Hameeteman, Wim H, additional, Romberg-Camps, Mariëlle J L, additional, Oostenbrug, Liekele E, additional, Masclee, Ad A M, additional, Jonkers, Daisy M A E, additional, and Pierik, Marieke J, additional

Published
2018
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8. Incidence and Classification of Postcolonoscopy Colorectal Cancers in Inflammatory Bowel Disease: A Dutch Population-Based Cohort Study

Author

Wintjens, Dion S. J., Wintjens, Dion S. J., Bogie, Roel M. M., van den Heuvel, Tim R. A., le Clercq, Chantal M. C., Oostenbrug, Liekele E., Romberg-Camps, Marielle J. L., Straathof, Jan-Willem, Stassen, Laurents P. S., Masclee, Ad A. M., Jonkers, Daisy M. A. E., Sanduleanu, Silvia, Pierik, Marie J., Wintjens, Dion S. J., Wintjens, Dion S. J., Bogie, Roel M. M., van den Heuvel, Tim R. A., le Clercq, Chantal M. C., Oostenbrug, Liekele E., Romberg-Camps, Marielle J. L., Straathof, Jan-Willem, Stassen, Laurents P. S., Masclee, Ad A. M., Jonkers, Daisy M. A. E., Sanduleanu, Silvia, and Pierik, Marie J.

Abstract

Background and Aims: Patients with inflammatory bowel disease [IBD] colitis are at increased risk for colorectal cancer [CRC]. We examined the proportion and most likely aetiology of potentially preventable postcolonoscopy CRCs [PCCRCs] in a population-based cohort. Furthermore, adherence to IBD surveillance guidelines was evaluated in both PCCRCs and the remainder of prevalent CRCs.Methods: All IBD patients diagnosed from 1991 to 2011 in the South Limburg region of The Netherlands [i.e. IBDSL cohort] were included. CRC cases were cross-checked with the Dutch pathology database and cancer registry. PCCRCs were defined as cancers diagnosed within 6-60 months after a colonoscopy and were classified as attributable to 'inappropriate surveillance interval', 'inadequate bowel examination', 'incomplete resection', 'missed lesion' or 'newly developed cancer'.Results: Twenty CRC cases were identified during 25,931 patient years of follow-up in 2,801 patients. The proportion of PCCRCs was 45.0%. Of these, 55.6% could be considered a 'missed lesion', while other possible aetiologies occurred only once. Considering both PCCRCs [n=9] and prevalent CRCs [n=11], ten were detected after publication of the surveillance guideline, but only three patients were enrolled. Moreover, 6 CRCs [30.0%] were detected before the recommended start of surveillance.Conclusions: In the IBDSL cohort, 45.0% of all CRCs were considered to be PCCRCs, mainly classified as missed lesions. Additionally, a large proportion of CRCs in our cohort were observed before a surveillance endoscopy was performed. Therefore, stringent adherence to IBD surveillance guidelines, improving endoscopy techniques and adjusting the surveillance program may lead to a decrease in CRC incidence.

Published
2018

9. Corticosteroid Sparing in Inflammatory Bowel Disease is More Often Achieved in the Immunomodulator and Biological Era-Results from the Dutch Population-Based IBDSL Cohort

Author

Jeuring, Steven F. G., Jeuring, Steven F. G., Biemans, Vince B. C., van den Heuvel, Tim R. A., Zeegers, Maurice P., Hameeteman, Wim H., Romberg-Camps, Marielle J. L., Oostenbrug, Liekele E., Masclee, Ad A. M., Jonkers, Daisy M. A. E., Pierik, Marieke J., Jeuring, Steven F. G., Jeuring, Steven F. G., Biemans, Vince B. C., van den Heuvel, Tim R. A., Zeegers, Maurice P., Hameeteman, Wim H., Romberg-Camps, Marielle J. L., Oostenbrug, Liekele E., Masclee, Ad A. M., Jonkers, Daisy M. A. E., and Pierik, Marieke J.

Abstract

OBJECTIVES: Corticosteroid-free remission is an emerging treatment goal in the management of inflammatory bowel disease (IBD). In the population-based Inflammatory Bowel Disease South Limburg cohort, we studied temporal changes in corticosteroid use and assessed the corticosteroid-sparing effects of immunomodulators and biologicals in real life.METHODS: In total, 2,823 newly diagnosed patients with Crohn's disease (CD) or ulcerative colitis (UC) were included. Corticosteroid exposure and cumulative days of use were compared between patients diagnosed in 1991-1998 (CD: n=316, UC: n=539), 1999-2005 (CD: n=387, UC: n=527), and 2006-2011 (CD: n=459, UC: n=595). Second, the corticosteroid-sparing effects of immunomodulators and biologicals were assessed.RESULTS: Over time, the corticosteroid exposure rate was stable (54.0% in CD and 31.4% in UC), even as the cumulative corticosteroid use in the first disease year (CD: 83 days (interquartile range (IQR) 35189), UC: 62 days (IQR 0-137)). On the long-term, a gradual decrease in cumulative corticosteroid use was seen in CD (era '91-'98: 366 days (IQR 107-841), era '06-'11: 120 days (IQR 72-211), PCONCLUSIONS: In a real-world setting, more recently diagnosed IBD patients used lower amounts of corticosteroids as of the second year of disease. For CD, a significant association was found with the use of immunomodulators and biologicals. These conclusions support the increasing use of these treatment modalities.

Published
2018

10. Inflammatory bowel disease, cancer and medication: Cancer risk in the Dutch population-based IBDSL cohort

Author

van den Heuvel, Tim R. A., Wintjens, Dion S. J., Jeuring, Steven F. G., Wassink, Maartje H. H., Romberg-Camps, Marielle J. L., Oostenbrug, Liekele E., Sanduleanu, Silvia, Hameeteman, Wim H., Zeegers, Maurice P., Masclee, Ad A., Jonkers, Daisy M., Pierik, Marieke, Interne Geneeskunde, Promovendi NTM, RS: NUTRIM - R2 - Gut-liver homeostasis, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Maag Darm Lever (9), RS: CAPHRI - R5 - Optimising Patient Care, RS: NUTRIM - R4 - Gene-environment interaction, and Complexe Genetica

Subjects
Crohn's disease, immunosuppression, inflammatory bowel disease, cancer, epidemiology, population based, ulcerative colitis
Abstract

The management of inflammatory bowel disease (IBD) has changed since the mid-1990s (e.g., use of thiopurines/anti-TNF alpha agents, improved surveillance programs), possibly affecting cancer risk. To establish current cancer risk in IBD, updates are warranted from cohorts covering this time span, and detailed enough to study associations with phenotype and medication. We studied intestinal-, extra-intestinal-and overall cancer risk in the Dutch population-based IBDSL cohort. In total, 1,157 Crohn's disease (CD) and 1,644 ulcerative colitis (UC) patients were diagnosed between 1991 and 2011, and followed until 2013. Standardized incidence ratios (SIRs) were calculated for CD and UC separately, as well as for gender- ,phenotype-, disease duration-, diagnosis era-and medication groups. We found an increased risk for colorectal cancer in CD patients with colon involvement (SIR 2.97; 95% CI 1.08-6.46), but not in the total CD or UC population. In addition, CD patients were at increased risk for hematologic-(2.41; 1.04-4.76), overall skin-(1.55; 1.06-2.19), skin squamous cell-(SCC; 3.83; 1.83-7.04) and overall cancer (1.28; 1.01-1.60), whereas UC patients had no increased risk for extra-intestinal-and overall cancer. Finally, in a medication analysis on CD and UC together, long-term immunosuppression exposure (> 12 months) was associated with an increased risk for hematologic cancer, non-Hodgkin lymphoma, SCC and overall cancer, and this increase was mainly attributed to thiopurines. IBD patients with long-term immunosuppression exposure can be considered as having a higher cancer risk, and our data support the advice in recent IBD guidelines to consider skin cancer screening in these patients.

Published
2016

11. Improvements in the Long-Term Outcome of Crohn's Disease Over the Past Two Decades and the Relation to Changes in Medical Management: Results from the Population-Based IBDSL Cohort

Author

Jeuring, Steven F. G., Jeuring, Steven F. G., van den Heuvel, Tim R. A., Liu, Limmie Y. L., Zeegers, Maurice P., Hameeteman, Wim H., Romberg-Camps, Marielle J. L., Oostenbrug, Liekele E., Masclee, Ad A. M., Jonkers, Daisy M. A. E., Pierik, Marieke J., Jeuring, Steven F. G., Jeuring, Steven F. G., van den Heuvel, Tim R. A., Liu, Limmie Y. L., Zeegers, Maurice P., Hameeteman, Wim H., Romberg-Camps, Marielle J. L., Oostenbrug, Liekele E., Masclee, Ad A. M., Jonkers, Daisy M. A. E., and Pierik, Marieke J.

Abstract

OBJECTIVES: Medical treatment options and strategies for Crohn's disease (CD) have changed over the past decades. To assess its impact, we studied the evolution of the long-term disease outcome in the Dutch Inflammatory Bowel Disease South Limburg (IBDSL) cohort.METHODS: In total, 1,162 CD patients were included. Three eras were distinguished: 1991-1998 (n=316), 1999-2005 (n=387), and 2006-2011 (n=459), and patients were followed until 2014. Medication exposure and the rates of hospitalization, surgery, and phenotype progression were estimated using Kaplan-Meier survival analyses and compared between eras by multivariable Cox regression models. Second, propensity score matching was used to assess the relation between medication use and the long-term outcome.RESULTS: Over time, the immunomodulator exposure rate increased from 30.6% in the era 1991-1998 to 70.8% in the era 2006-2011 at 5 years. Similar, biological exposure increased from 3.1% (era 1991-1998) to 41.2% (era 2006-2011). In parallel, the hospitalization rate attenuated from 65.9% to 44.2% and the surgery rate from 42.9% to 17.4% at 5 years, respectively (both P0.05 for all analyses). Similar results were found for biological users (P>0.05 for all analyses).CONCLUSIONS: Between 1991 and 2014, the hospitalization and surgery rates decreased, whereas progression to complicated disease is still common in CD. These improvements were not significantly related to the use of immunomodulators and biologicals.

Published
2017

12. Better survival of renal cell carcinoma in patients with inflammatory bowel disease

Author

Derikx, Lauranne A. A. P., Nissen, Loes H. C., Drenth, Joost P. H., van Herpen, Carla M., Kievit, Wietske, Verhoeven, Rob H. A., Mulders, Peter F. A., Hulsbergen-van de Kaa, Christina A., Boers-Sonderen, Marye J., van den Heuvel, Tim R. A., Pierik, Marieke, Nagtegaal, Iris D., Hoentjen, Frank, Kluin, P. M., Hogenes, M., Hamel, A. F., Natté, R., van Dijk, C. M., Kusters-Vandevelde, H. V. N., Sastrowijoto, S. H., Willig, A. P., Dijkstra, G., van der Meulen-de Jong, A. E., Vu, M. K., Cats, A., Haanen, J. B. A. G., van der Woude, C. J., Russel, M. G. V. M., Oldenburg, B., Meeuse, J. J., Corporaal, S., Zonneveld, A. M., Wahab, P. J., van den Hazel, S. J., Mares, W. G. N., Lieverse, R. J., Meijssen, M. A. C., Thuernau, K., Janik, D., van der Heide, H., Ponsioen, C. Y., Stokkers, P. C. F., Gastroenterology and Hepatology, Interne Geneeskunde, and RS: NUTRIM - R2 - Gut-liver homeostasis

Subjects
Male, Time Factors, Kaplan-Meier Estimate, urologic and male genital diseases, Inflammatory bowel disease, Crohn Disease, Risk Factors, Renal cell carcinoma, Odds Ratio, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Medicine, Registries, Early Detection of Cancer, Netherlands, Aged, 80 and over, education.field_of_study, Age Factors, Middle Aged, Prognosis, Kidney Neoplasms, female genital diseases and pregnancy complications, Oncology, Cohort, Female, medicine.symptom, Immunosuppressive Agents, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, renal cell carcinoma, Pancolitis, medicine.medical_specialty, Population, immunosuppressive therapy, Risk Assessment, Immunocompromised Host, Predictive Value of Tests, inflammatory bowel disease, Internal medicine, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Humans, education, Carcinoma, Renal Cell, Aged, Proportional Hazards Models, Retrospective Studies, Chi-Square Distribution, Tumor Necrosis Factor-alpha, business.industry, Retrospective cohort study, Odds ratio, medicine.disease, digestive system diseases, Surgery, Cancer registry, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Multivariate Analysis, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Colitis, Ulcerative, Clinical Research Paper, business
Abstract

// Lauranne A.A.P. Derikx 1 , Loes H.C. Nissen 1 , Joost P.H. Drenth 1 , Carla M. van Herpen 2 , Wietske Kievit 3 , Rob H.A. Verhoeven 4 , Peter F.A. Mulders 5 , Christina A. Hulsbergen-van de Kaa 6 , Marye J. Boers-Sonderen 2 , Tim R.A. van den Heuvel 7 , Marieke Pierik 7 , Iris D. Nagtegaal 6 , Frank Hoentjen 1 , On behalf of the Dutch Initiative on Crohn and Colitis (ICC), PALGA group and IBD/RCC group 1 Inflammatory Bowel Disease Centre, Department of Gastroenterology and Hepatology, Radboud university medical centre, Nijmegen, The Netherlands 2 Department of Medical Oncology, Radboud university medical centre, Nijmegen, The Netherlands 3 Radboud Institute for Health Sciences, Radboud university medical centre, Nijmegen, The Netherlands 4 Netherlands comprehensive cancer organization / Netherlands Cancer Registry, Utrecht, The Netherlands 5 Department of Urology, Radboud university medical centre, Nijmegen, The Netherlands 6 Department of Pathology, Radboud university medical centre, Nijmegen, The Netherlands 7 Department of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands Correspondence to: Lauranne A.A.P. Derikx, e-mail: Lauranne.Derikx@radboudumc.nl Keywords: inflammatory bowel disease, renal cell carcinoma, immunosuppressive therapy Received: June 30, 2015 Accepted: September 24, 2015 Published: October 05, 2015 ABSTRACT Background: Immunosuppressive therapy may impact cancer risk in inflammatory bowel disease (IBD). Cancer specific data regarding risk and outcome are scarce and data for renal cell carcinoma (RCC) are lacking. We aimed(1) to identify risk factors for RCC development in IBD patients (2) to compare RCC characteristics, outcome and survival between IBD patients and the general population. Methods: A PALGA (Dutch Pathology Registry) search was performed to establish a case group consisting of all IBD patients with incident RCC in The Netherlands (1991–2013). Cases were compared with two separate control groups: (A) with a population-based IBD cohort for identification of risk factors (B) with a RCC cohort from the general population to compare RCC characteristics and outcomes. Results: 180 IBD patients with RCC were identified. Pancolitis (OR 1.8–2.5), penetrating Crohn’s disease (OR 2.8), IBD related surgery (OR 3.7–4.5), male gender (OR 3.2–5.0) and older age at IBD onset (OR 1.0–1.1) were identified as independent risk factors for RCC development. IBD patients had a significantly lower age at RCC diagnosis ( p < 0.001), lower N-stage ( p = 0.025), lower M-stage ( p = 0.020) and underwent more frequently surgical treatment for RCC ( p < 0.001) compared to the general population. This translated into a better survival ( p = 0.026; HR 0.7) independent of immunosuppression. Conclusions: IBD patients with a complex phenotype are at increased risk to develop RCC. They are diagnosed with RCC at a younger age and at an earlier disease stage compared to the general population. This translates into a better survival independent of immunosuppressive or anti-TNFα therapy.

Published
2015

13. Improvements in the Long-Term Outcome of Crohn’s Disease Over the Past Two Decades and the Relation to Changes in Medical Management: Results from the Population-Based IBDSL Cohort

Author

Jeuring, Steven F G, primary, van den Heuvel, Tim R A, additional, Liu, Limmie Y L, additional, Zeegers, Maurice P, additional, Hameeteman, Wim H, additional, Romberg-Camps, Mariëlle J L, additional, Oostenbrug, Liekele E, additional, Masclee, Ad A M, additional, Jonkers, Daisy M A E, additional, and Pierik, Marieke J, additional

Published
2017
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15. Cohort Profile: The Inflammatory Bowel Disease South Limburg Cohort (IBDSL).

Author

van den Heuvel, Tim R. A., Jonkers, Daisy M., Jeuring, Steven F. G., Romberg-Camps, Marielle J. L., Oostenbrug, Liekele E., Zeegers, Maurice P., Masclee, Ad A., Pierik, Marie J., van den Heuvel, Tim Ra, Jeuring, Steven Fg, and Romberg-Camps, Marielle Jl

Subjects
*INFLAMMATORY bowel diseases, *CROHN'S disease, *ULCERATIVE colitis, *INTESTINAL diseases, *CHRONIC diseases
Published
2017
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17. Ambient air quality as risk factor for microscopic colitis - A geographic information system (GIS) study.

Author

Verhaegh BPM, Bijnens EM, van den Heuvel TRA, Goudkade D, Zeegers MP, Nawrot TS, Masclee AAM, Jonkers DMAE, and Pierik MJ

Subjects
Case-Control Studies, Female, Humans, Male, Netherlands epidemiology, Risk Factors, Air Pollutants analysis, Air Pollution statistics & numerical data, Colitis, Microscopic epidemiology, Environmental Exposure statistics & numerical data, Geographic Information Systems
Abstract

Background: Microscopic colitis (MC) is considered a multifactorial disease, strongly associated with smoking. However, little is known about the role of environmental factors such as ambient air pollution in MC pathophysiology. There is an overlap in components of cigarette smoke and ambient air pollution. Therefore, the aim of this study was to explore an independent association between ambient air quality and MC., Methods: A case-control study was performed. MC cases in South Limburg, the Netherlands, diagnosed between 2000 and 2012, were retrieved from the national pathology registry and matched to non-MC controls from the same area based on age (±2 years) and gender. A stable residential address for ≥3 years was required. Residential land use, proximity to major road, and concentrations of air pollution compounds, were determined using a Geographic Information System (GIS). Univariate and multivariable regression analyses were corrected for age, gender and smoking status., Results: In total, 345 MC cases (78.6% female) and 583 matched controls (77.2% female) were included. In the univariate analyses, the percentage of urban green within a 500 m buffer and residential proximity to the nearest highway were associated with MC (both p < 0.10). On the multivariable level only a higher age at diagnosis (OR 1.02, 95%-CI 1.01-1.04) and current smoking at index date (OR 4.30; 95%-CI 3.01-6.14) were significantly associated with MC., Conclusion: Based on the current findings, ambient air quality does not seem to be an important risk factor for MC, in contrast to the well-known risk factors age and current smoking., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Published
2019
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18. Development and Validation of a Patient-reported Score to Screen for Mucosal Inflammation in Inflammatory Bowel Disease.

Author

de Jong MJ, Roosen D, Degens JHRJ, van den Heuvel TRA, Romberg-Camps M, Hameeteman W, Bodelier AGL, Romanko I, Lukas M, Winkens B, Markus T, Masclee AAM, van Tubergen A, Jonkers DMAE, and Pierik MJ

Subjects
Adult, Colitis pathology, Colitis, Ulcerative diagnosis, Colitis, Ulcerative pathology, Colonoscopy, Crohn Disease diagnosis, Crohn Disease pathology, Feces chemistry, Female, Humans, Inflammatory Bowel Diseases pathology, Intestinal Mucosa pathology, Leukocyte L1 Antigen Complex analysis, Male, Middle Aged, Prospective Studies, Reproducibility of Results, Surveys and Questionnaires, Inflammatory Bowel Diseases diagnosis, Patient Reported Outcome Measures
Abstract

Background and Aims: Patient-reported outcome measures [PROMs] assessing inflammatory bowel disease [IBD] activity are of interest for monitoring in clinical practice, telemedicine systems, or trials. Different PROMs for follow-up of disease activity are available; however, none was developed with endoscopy as gold standard. The objective of this study was to develop and validate a PROM to predict endoscopic disease activity, following the recommendations of the Food and Drug Administration., Methods: During development, 178 IBD patients undergoing a colonoscopy were asked to fill out 13 clinical questions derived from the literature. During endoscopy, inflammation was assessed with the simplified endoscopic score for Crohn's disease [CD] and the Mayo endoscopic subscore for ulcerative colitis [UC]. Based on correlation with endoscopic inflammation, questions were reduced to a total of six for CD and five for UC. The newly developed Monitor IBD At Home questionnaire [MIAH] was validated in an independent cohort of 135 CD and 131 UC patients. Additionally, diagnostic accuracy of the MIAH combined with a calprotectin home test [CHT] was assessed., Results: The MIAH-CD includes questions on rectal bleeding, mucus, stool frequency, urgency, fatigue, and patient-reported disease activity. The MIAH-UC contains items on rectal bleeding, stool frequency, urgency, abdominal pain, and patient-reported disease activity. Both questionnaires showed to be valid, reliable, and responsive to changes. The MIAH and CHT combined had a sensitivity, specificity, negative predictive value [NPV], and positive predicitive value [PPV] of 96.7%, 66.7%, 94.7%, and 76.3% for CD and of 88.2%, 81.4%, 95.6%, and 60.0% for UC, respectively, compared with endoscopy., Conclusions: The MIAH is the first PROM developed to predict endoscopic inflammation in IBD patients. A combination of this questionnaire and a CHT shows excellent diagnostic accuracy to screen for patients who need further assessment of disease activity, and can be used in daily practice, telemedicine systems, and trials., (Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2019
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19. Inflammatory bowel disease, cancer and medication: Cancer risk in the Dutch population-based IBDSL cohort.

Author

van den Heuvel TR, Wintjens DS, Jeuring SF, Wassink MH, Romberg-Camps MJ, Oostenbrug LE, Sanduleanu S, Hameeteman WH, Zeegers MP, Masclee AA, Jonkers DM, and Pierik MJ

Subjects
Adult, Aged, Cohort Studies, Female, Follow-Up Studies, Humans, Immunosuppression Therapy methods, Incidence, Inflammatory Bowel Diseases diagnosis, Inflammatory Bowel Diseases therapy, Male, Middle Aged, Neoplasms diagnosis, Netherlands epidemiology, Phenotype, Population Surveillance, Risk, Immunosuppression Therapy adverse effects, Inflammatory Bowel Diseases complications, Neoplasms epidemiology, Neoplasms etiology
Abstract

The management of inflammatory bowel disease (IBD) has changed since the mid-1990s (e.g., use of thiopurines/anti-TNFα agents, improved surveillance programs), possibly affecting cancer risk. To establish current cancer risk in IBD, updates are warranted from cohorts covering this time span, and detailed enough to study associations with phenotype and medication. We studied intestinal-, extra-intestinal- and overall cancer risk in the Dutch population-based IBDSL cohort. In total, 1,157 Crohn's disease (CD) and 1,644 ulcerative colitis (UC) patients were diagnosed between 1991 and 2011, and followed until 2013. Standardized incidence ratios (SIRs) were calculated for CD and UC separately, as well as for gender-, phenotype-, disease duration-, diagnosis era- and medication groups. We found an increased risk for colorectal cancer in CD patients with colon involvement (SIR 2.97; 95% CI 1.08-6.46), but not in the total CD or UC population. In addition, CD patients were at increased risk for hematologic- (2.41; 1.04-4.76), overall skin- (1.55; 1.06-2.19), skin squamous cell- (SCC; 3.83; 1.83-7.04) and overall cancer (1.28; 1.01-1.60), whereas UC patients had no increased risk for extra-intestinal- and overall cancer. Finally, in a medication analysis on CD and UC together, long-term immunosuppression exposure (>12 months) was associated with an increased risk for hematologic cancer, non-Hodgkin lymphoma, SCC and overall cancer, and this increase was mainly attributed to thiopurines. IBD patients with long-term immunosuppression exposure can be considered as having a higher cancer risk, and our data support the advice in recent IBD guidelines to consider skin cancer screening in these patients., (© 2016 UICC.)

Published
2016
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20. Better survival of renal cell carcinoma in patients with inflammatory bowel disease.

Author

Derikx LA, Nissen LH, Drenth JP, van Herpen CM, Kievit W, Verhoeven RH, Mulders PF, Hulsbergen-van de Kaa CA, Boers-Sonderen MJ, van den Heuvel TR, Pierik M, Nagtegaal ID, and Hoentjen F

Subjects
Adult, Age Factors, Aged, Aged, 80 and over, Carcinoma, Renal Cell diagnosis, Carcinoma, Renal Cell immunology, Carcinoma, Renal Cell mortality, Carcinoma, Renal Cell therapy, Chi-Square Distribution, Colitis, Ulcerative diagnosis, Colitis, Ulcerative drug therapy, Colitis, Ulcerative immunology, Colitis, Ulcerative mortality, Crohn Disease diagnosis, Crohn Disease drug therapy, Crohn Disease immunology, Crohn Disease mortality, Early Detection of Cancer, Female, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Kaplan-Meier Estimate, Kidney Neoplasms diagnosis, Kidney Neoplasms immunology, Kidney Neoplasms mortality, Kidney Neoplasms therapy, Male, Middle Aged, Multivariate Analysis, Netherlands epidemiology, Odds Ratio, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Registries, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha immunology, Carcinoma, Renal Cell epidemiology, Colitis, Ulcerative epidemiology, Crohn Disease epidemiology, Kidney Neoplasms epidemiology
Abstract

Background: Immunosuppressive therapy may impact cancer risk in inflammatory bowel disease (IBD). Cancer specific data regarding risk and outcome are scarce and data for renal cell carcinoma (RCC) are lacking. We aimed(1) to identify risk factors for RCC development in IBD patients (2) to compare RCC characteristics, outcome and survival between IBD patients and the general population., Methods: A PALGA (Dutch Pathology Registry) search was performed to establish a case group consisting of all IBD patients with incident RCC in The Netherlands (1991-2013). Cases were compared with two separate control groups: (A) with a population-based IBD cohort for identification of risk factors (B) with a RCC cohort from the general population to compare RCC characteristics and outcomes., Results: 180 IBD patients with RCC were identified. Pancolitis (OR 1.8-2.5), penetrating Crohn's disease (OR 2.8), IBD related surgery (OR 3.7-4.5), male gender (OR 3.2-5.0) and older age at IBD onset (OR 1.0-1.1) were identified as independent risk factors for RCC development. IBD patients had a significantly lower age at RCC diagnosis (p < 0.001), lower N-stage (p = 0.025), lower M-stage (p = 0.020) and underwent more frequently surgical treatment for RCC (p < 0.001) compared to the general population. This translated into a better survival (p = 0.026; HR 0.7) independent of immunosuppression., Conclusions: IBD patients with a complex phenotype are at increased risk to develop RCC. They are diagnosed with RCC at a younger age and at an earlier disease stage compared to the general population. This translates into a better survival independent of immunosuppressive or anti-TNFα therapy.

Published
2015
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21. Disease Outcome of Ulcerative Colitis in an Era of Changing Treatment Strategies: Results from the Dutch Population-Based IBDSL Cohort.

Author

Jeuring SF, Bours PH, Zeegers MP, Ambergen TW, van den Heuvel TR, Romberg-Camps MJ, van Bodegraven AA, Oostenbrug LE, Breukink SO, Stassen LP, Hameeteman WH, Masclee AA, Jonkers DM, and Pierik MJ

Subjects
Adult, Cohort Studies, Colitis, Ulcerative complications, Colitis, Ulcerative diagnosis, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Netherlands, Proportional Hazards Models, Time Factors, Treatment Outcome, Colectomy, Colitis, Ulcerative therapy, Hospitalization, Immunologic Factors therapeutic use
Abstract

Background and Aims: In the past decades, treatment options and strategies for ulcerative colitis [UC] have radically changed. Whether these developments have altered the disease outcome at population level is yet unknown. Therefore, we evaluated the disease outcome of UC over the past two decades in the South-Limburg area of The Netherlands., Methods: In the Dutch population-based IBDSL cohort, three time cohorts were defined: cohort 1991-1997 [cohort A], cohort 1998-2005 [cohort B], and cohort 2006-2010 [cohort C]. The colectomy and hospitalisation rates were compared between cohorts by Kaplan-Meier survival analyses. Hazard ratios [HR] for early colectomy [within 6 months after diagnosis], late colectomy [beyond 6 months after diagnosis], and hospitalisation were calculated using Cox regression models., Results: In total, 476 UC patients were included in cohort A, 587 patients in cohort B, and 598 patients in cohort C. Over time, an increase in the use of immunomodulators [8.1%, 22.8% and 21.7%, respectively, p < 0.01] and biological agents [0%, 4.3% and 10.6%, respectively, p < 0.01] was observed. The early colectomy rate decreased from 1.5% in cohort A to 0.5% in cohort B [HR 0.14; 95% confidence interval 0.04-0.47], with no further decrease in cohort C [0.3%, HR 0.98; 95% confidence interval 0.20-4.85]. Late colectomy rate remained unchanged over time [4.0% vs 5.2% vs 3.6%, respectively, p = 0.54]. Hospitalisation rate was also similar among cohorts [22.3% vs 19.5% vs 18.3%, respectively, p = 0.10]., Conclusion: Over the past two decades, a reduction in early colectomy rate was observed, with no further reduction in the most recent era. Late colectomy rate and hospitalisation rate remained unchanged over time., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2015
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