http://repub.eur.nl/res/aut/49053/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/40054/ 2013-06-01T00:00:00Z The aim of this study is to assess time trends of the risk of melanoma as a second primary cancer (MSPC) among cancer patients in the Netherlands during 1989-2008. Data from the population-based Netherlands Cancer Registry (NCR) were used for an analysis of time trends in the risk of MSPC in a fixed inception cohorts design (1989-1990, 1996-1997, and 2003), with similar lengths of follow-up. Standardized incidence ratios and absolute excess risks (AERs) were calculated to estimate the relative risks and excess absolute risks of MSPC. Differential time trends of risk in MSPC were observed, that is, decreasing for standardized incidence ratios and increasing for AERs in both sexes, but not reaching significance. Over time, AER changed from 24 to 72 per 10 000 person years (P for trend=0.01) in male patients with a previous melanoma during 2-5 years of follow-up, whereas among women with a first squamous cell carcinoma of skin, AER increased markedly (P for trend=0.3) over time during the first year of follow-up, coinciding with a decrease during the 2-5 years of the follow-up period (P for trend=0.1). MSPCs diagnosed later during follow-up were thicker than those diagnosed earlier, this difference being only statistically significant among male patients with a previous melanoma. The observed favorable risk trend among female patients coincided with thicker MSPCs than male patients. Differential risk trends were observed for MSPC among cancer patients during the past two decades in the Netherlands that did not seem to be affected by greater awareness of the disease. As the stage distribution of MSPCs worsened during follow-up, efforts should be made towards an earlier diagnosis of MSPC. http://repub.eur.nl/res/pub/39928/ 2013-04-22T00:00:00Z In this systematic review and meta-analysis the risk of a subsequent basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or melanoma in patients with a previous keratinocyte carcinoma (KC) was investigated. PubMed, Embase, Web of Science and the Cochrane library were searched for studies published before 1st January 2012 that reported risks (i.e. proportions, cumulative risks or standardised incidence ratios [SIR]) of developing a subsequent BCC, SCC or melanoma in patients with prior KC. 45 articles fulfilled the inclusion criteria. In BCC patients, the pooled proportion for a subsequent BCC, SCC or melanoma was respectively 29.2% (95% confidence interval (CI) 24.6-34.3%), 4.3% (1.7-10.1%) and 0.5% (0.4-0.8%). The pooled proportion of a subsequent SCC, BCC or melanoma in SCC patients was respectively 13.3% (95% CI 7.4-22.8%), 15.9% (5.6-37.6%) and 0.5% (0.3-0.6%). The pooled SIRs for a subsequent BCC, SCC or melanoma were respectively 17.4 (95% CI 0.0-37.4), 3.2 (0.0-6.5) and 2.4 (2.3-2.6) in BCC and 4.2 (95% CI 2.0-6.5), 15.0 (14.0-16.0) and 2.7 (2.3-3.2) in SCC patients. In the subgroup analyses, strongest differences in risks were found in the continent strata (risks Australia > North America > Europe). http://repub.eur.nl/res/pub/38488/ 2012-12-01T00:00:00Z Background Patients with melanoma are at increased risk of developing a subsequent melanoma. Objectives To estimate the risks of developing a second primary in situ or invasive cutaneous melanoma after a first melanoma, between 1989 and 2008. Methods Patients were followed until diagnosis of a second melanoma, date of death or end of study. Cumulative risks, standardized incidence ratio (SIR, observed second melanomas divided by background age-, calendar- and sex-specific incidence rates of melanoma, as recorded in the Netherlands Cancer Registry) and absolute excess risk (AER, observed minus expected per 10 000 person-years) of second melanomas were calculated. Results In total, 10 765 patients with in situ melanoma and 46 700 with invasive melanoma were included. The cumulative risks of a second invasive melanoma after a first in situ or invasive melanoma at 20 years of follow-up were 6·2% and 5·0%, respectively. The relative risk of developing any melanoma (in situ or invasive) after any first melanoma (measured as SIR) varied from 12·4-fold [invasive after invasive melanoma; 95% confidence interval (CI) = 11·6-13·2] to 26·4-fold (in situ after in situ melanoma; 95% CI = 22·6-30·7) increase compared with the general population. SIRs and AERs remained elevated up to 20 years after the first melanoma. Conclusions This study shows significantly increased long-term risks (both relative and absolute) of developing a second invasive melanoma after a first melanoma (invasive and in situ), and might serve as a basis for follow-up guidelines. © 2012 The Authors. BJD http://repub.eur.nl/res/pub/38516/ 2012-11-29T00:00:00Z Basal cell carcinoma (BCC) incidence rates are increasing. From 1973 to 2009, data on all first histologically confirmed BCCs were gained from the Eindhoven Cancer Registry to estimate trends in patient-based BCC incidence rates by sex, age group, and site in the southeast Netherlands. Trends in European age-standardized rates and age- and site-specific incidence rates were assessed by calculating the estimated annual percentage change (EAPC). Between 1973 and 2009, the European standardized rate quadrupled from 40 to 165 per 100,000 person-years for men and from 34 to 157 for women, significantly increasing since 1973 in both sexes, but accelerating from 2002 until 2009 with an EAPC of 6.8% (95% confidence interval (CI), 5.3-8.3) for men and 7.9% (95% CI, 6.2-9.7) for women. Women below the age of 40 years exhibited a constant linear increase of 6.3% since 1973. The head and neck region was most often affected in both sexes, but the steepest increase was seen for the trunk (EAPC men 13%, women 15%). In the absence of reliable tumor-based rates, these alarming patient-based rates are probably an interesting indicator for the impact of more intensive UV exposure in a prosperous European population.Journal of Investigative Dermatology advance online publication, 29 November 2012; doi:10.1038/jid.2012.431. http://repub.eur.nl/res/pub/38854/ 2012-11-01T00:00:00Z Background Melanoma incidence and mortality in Europe are high but there are significant gaps in the epidemiological information available across the continent. Objectives With the aim of enhancing the planning of educational programmes for reducing the melanoma burden in Europe, we analysed the most recent incidence and mortality data for Europe with a new focus on the regional disparities of melanoma reporting. Methods GLOBOCAN 2008, the standard set of worldwide estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer for 2008, was used to provide the estimated age-standardized rates (world standard population) of melanoma incidence and mortality in European countries and regions. Results The estimated age-standardized incidence of melanoma (measured per 100 000 person-years) varies widely from 19·2 in Switzerland to 2·2 in Greece. The incidence rate of 4·3 of Central and Eastern Europe (CEE) is less than half of that of Western Europe. Melanoma mortality rates of 1·5 are similar in CEE and Western Europe, although rates vary with a high of 3·2 in Norway and a low of 0·9 in Greece. Over 20 000 deaths from melanoma were estimated in Europe in 2008, with CEE having the largest share (35·5%) among the four geographical European regions. Population-based data are lacking for significant parts of CEE, which must rely on estimates. Conclusions The most recent estimates of melanoma incidence and mortality in Europe reveal sharp differences between European countries, possibly related to missed opportunities for early diagnosis and incomplete reporting of melanoma in Eastern Europe. © 2012 The Authors. BJD http://repub.eur.nl/res/pub/33166/ 2011-12-22T00:00:00Z Common variable immunodeficiency disorder (CVID) is the most prevalent form of primary idiopathic hypogammaglobulinemia. Identification of genetic defects in CVID is hampered by clinical and immunologic heterogeneity. By flow cytometric immunophenotyping and cell sorting of peripheral B-cell subsets of 37 CVID patients, we studied the B-cell compartment at the B-cell subset level using the κ-deleting recombination excision circle assay to determine the replication history and the Igκ-restriction enzyme hot-spot mutation assay to assess the somatic hypermutation status. Using this approach, 5 B-cell patterns were identified, which delineated groups with unique replication and somatic hypermutation characteristics. Each B-cell pattern reflected an immunologically homogenous patient group for which we proposed a different pathophysiology: (1) a B-cell production defect (n ∇ 8, 18%), (2) an early peripheral B-cell maturation or survival defect (n ∇ 4, 11%), (3) a B-cell activation and proliferation defect (n ∇ 12, 32%), (4) a germinal center defect (n ∇ 7, 19%), and (5) a postgerminal center defect (n ∇ 6, 16%). The results of the present study provide for the first time insight into the underlying pathophysiologic background in 5 immunologically homogenous groups of CVID patients. Moreover, this study forms the basis for larger cohort studies with the defined homogenous patient groups and will facilitate the identification of underlying genetic defects in CVID.