Dermatology

Trends of cutaneous squamous cell carcinoma in the Netherlands: increased incidence rates, but stable relative survival and mortality 1989-2008 (Article)

Hollestein, L.M. — 2012-02-16T00:00:00Z

Abstract Background Incidence rates of cutaneous squamous cell carcinoma (SCC) are increasing in many countries, though detailed information is scarce. Objectives To describe detailed trends in incidence rates, relative survival and estimate mortality rates of SCC in the Netherlands. Methods Information on newly diagnosed SCC patients between 1989 and 2008 was obtained from the Netherlands Cancer Registry (NCR). Information of non-melanoma skin cancer (NMSC) mortality was obtained from Statistics Netherlands. European Standardised Rates (ESR) and Estimated Annual Percentage Change (EAPC) were calculated. Incidence rates were fitted to two different models and predicted by the best fitted model. Cohort-based and multivariate survival analyses were performed to assess changes over time. Results The ESR increased from 22.2 to 35.4 per 100,000 inhabitants for males and from 7.8 to 20.5 for females. The EAPC was 6.9% (95% confidence interval: 5.8–8.7) for males and 9.2% (95% CI: 7.5–11.0) for females. Incidence rates increased for all body sites, except for the lips, where a decreasing trend for males was observed. The predicted ESR in 2020 is 46.9 per 100,000 inhabitants for males and 28.7 for females. The 5-year relative survival rate was 92.0% (95% CI: 91.3–92.8) for males and 94.9% (95% CI: 94.0–95.7) for females and remained stable over time. Overall relative survival was better for females, but females with advanced disease had a 30.4 relative excess risk of dying compared to those in stage I. This difference was 9.9 for men. The estimated mortality rate decreased with –1.9% (95% CI: –3.1% to –0.7%) annually. Conclusions Incidence rates of SCC increased rapidly. Relative survival was high, as most SCCs were diagnosed in stage I. Nevertheless, the number of newly diagnosed patients may exceed 11,000 by 2020, emphasising the need to improve methods to prevent skin cancer.

Letter: Pigmented bowen's disease: A report of two cases (Article)

Vries, N.K. de — 2011-07-01T00:00:00Z

Endovenous treatments for varicose veins (Doctoral Thesis)

Bos, R.R. van den — 2011-06-22T00:00:00Z

Endovenous treatment is currently one of the most frequently used methods for treating varicose veins in the Netherlands. Varicose veins are tortuous and enlarged veins due to weakening in the vein’s wall or valves. They are manifestations of chronic venous disease (CVD), which may lead to serious complications.

Increased risk of infectious disease requiring hospitalization among patients with psoriasis: A population-based cohort (Article)

Wakkee, M. — 2011-06-10T00:00:00Z

Background: Immunologic alterations caused by psoriasis and/or its therapies may affect the risk of serious infections. Objective: For patients with psoriasis, we explored the overall and therapy-related risk of contracting an infectious disease (ID) requiring hospitalization in a large population-based cohort. Methods: The incidence of ID was compared between patients with psoriasis and a randomly selected cohort (ratio 1:5) using hospital and pharmacy databases covering 2.5 million Dutch residents between 1997 and 2008. First and multiple IDs were defined and categorized into 20 groups based on primary International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnoses. Multivariate Cox regression and Poisson event-count models were used to test the risk difference of IDs between patients with psoriasis and reference cohort. Results: A total of 25,742 patients with psoriasis and 128,710 reference subjects were followed up for approximately 6 years. The likelihood of IDs in patients with psoriasis was twice as high as the reference population (908 vs 438 events/100,000 person-years, crude hazard ratio 2.08, 95% confidence interval 1.96-2.22). In a multivariate model the hazard ratio decreased to 1.54 (95% confidence interval 1.44-1.65). This risk was highest for patients with more severe psoriasis (adjusted hazard ratio 1.81, 95% confidence interval 1.57-2.08), but was not associated with recent systemic antipsoriatic drug dispensing. Respiratory tract, abdominal, and skin infections occurred most frequently in patients with psoriasis. Multiple event analysis that counted the total number of infectious discharge diagnoses gave similar results. Limitations: No data were available on lifestyle factors. Conclusion: The risk of severe infections was significantly higher for patients with psoriasis compared with control subjects and could not be explained by exposure to systemic antipsoriatic drugs.

Elevated levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 in hidradenitis suppurativa skin: A rationale for targeting TNF-α and IL-1β (Article)

Zee, H.H. van der — 2011-06-01T00:00:00Z

Background The pathogenesis of hidradenitis suppurativa (HS) is largely unknown and the disease is difficult to treat. Patients are in high need of an effective treatment. Although it is not known whether the levels of tumour necrosis factor (TNF)-α are aberrant in HS skin, anti-TNF-α biologics are used, with variable clinical efficacy. Objectives To determine the cytokine profile in lesional and perilesional HS skin. Methods We cultured 20 lesional and 10 normal-appearing perilesional HS skin samples, seven psoriasis and six healthy control skin samples in a transwell culture system. Two distinct cytokine bead arrays were used to measure the spectrum of inflammatory cytokines in the culture supernatant. Results from HS skin samples were compared with those of healthy and psoriasis skin. Results The proinflammatory cytokines interleukin (IL)-1β and TNF-α as well as the anti-inflammatory cytokine IL-10 were significantly elevated in HS skin. Elevated levels of these cytokines were also found in perilesional HS skin. Fold increases relative to control skin of IL-1β, TNF-α and IL-10 in HS were 31, 5 and 34, compared with psoriasis: 4, 1 and 2, respectively. Levels of all three cytokines showed a trend towards a positive correlation with disease severity. IL-2, IL-4, IL-5 and interferon-γ were hardly detectable in HS or healthy control skin. Conclusions This study shows for the first time that IL-1β, TNF-α and IL-10 levels are elevated in HS skin. These data provide a rationale for therapies with biologics targeting cytokines such as TNF-α and IL-1. © 2011 The Authors. BJD

GATA3 expression is decreased in psoriasis and during epidermal regeneration; induction by narrow-band UVB and IL-4 (Article)

Rácz, E. — 2011-05-23T00:00:00Z

Psoriasis is characterized by hyperproliferation of keratinocytes and by infiltration of activated Th1 and Th17 cells in the (epi)dermis. By expression microarray, we previously found the GATA3 transcription factor significantly downregulated in lesional psoriatic skin. Since GATA3 serves as a key switch in both epidermal and T helper cell differentiation, we investigated its function in psoriasis. Because psoriatic skin inflammation shares many characteristics of epidermal regeneration during wound healing, we also studied GATA3 expression under such conditions. Psoriatic lesional skin showed decreased GATA3 mRNA and protein expression compared to non-lesional skin. GATA3 expression was also markedly decreased in inflamed skin of mice with a psoriasiform dermatitis induced with imiquimod. Tape-stripping of non-lesional skin of patients with psoriasis, a standardized psoriasis-triggering and skin regeneration-inducing technique, reduced the expression of GATA3. In wounded skin of mice, low GATA3 mRNA and protein expression was detected. Taken together, GATA3 expression is downregulated under regenerative and inflammatory hyperproliferative skin conditions. GATA3 expression could be re-induced by successful narrow-band UVB treatment of both human psoriasis and imiquimod-induced psoriasiform dermatitis in mice. The prototypic Th2 cytokine IL-4 was the only cytokine capable of inducing GATA3 in skin explants from healthy donors. Based on these findings we argue that GATA3 serves as a key regulator in psoriatic inflammation, keratinocyte hyperproliferation and skin barrier dysfunction.

Rhabdoid tumor mimicking hemangioma (Article)

Assen, Y.J. — 2011-05-01T00:00:00Z

We report a young boy with a malignant tumor, which remained unrecognized for 8 months because it was assumed to be a hemangioma. The presentation of a rhabdoid tumor mimicking hemangioma is very rare. It was reported only on two earlier occasions. Rhabdoid tumors are one of the most aggressive types of malignancies encountered in pediatric oncology. It is important to recognize that a fast growing vascular lesion in a child will often be a hemangioma, but could also be an aggressive tumor.

Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis (Article)

Swindell, W.R. — 2011-04-11T00:00:00Z

Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.

A longitudinal study of changes in provider-patient interaction in treatment of localized prostate cancer (Article)

Ernstmann, N. — 2011-04-11T00:00:00Z

Purpose: Whilst much is known as to the met and unmet communication needs of prostate cancer patients, few studies have been conducted on the changes in communication between provider and patient over time. Therefore, the aim of our study is to examine (a) whether there are changes over time in the quality of psychosocial care in long-term treatment of localized prostate cancer and (b) whether those changes are associated with the treatment decision. Methods: HAROW is a prospective, observational study designed to collect clinical data and patient reported outcomes (PROs) of different treatment options (hormonal therapy, active surveillance, radiation, operation, watchful waiting) for newly diagnosed patients with localized prostate cancer under real conditions. At 6-month intervals, general clinical data, PROs (e.g. quality of life, quality of physician-patient interaction) and individual costs are documented. We analysed data of N = 1,216 patients at the time of initial diagnosis (T1) and after 6 months (T2). Results: There is a significant decline in shared decision-making behaviour of physicians for the group of patients undergoing a prostatectomy and for the hormonal therapy group at the time of initial diagnosis and after 6 months. In terms of emotional support by physicians, there is a significant difference between the treatment groups at the time of initial diagnosis with patients undergoing a prostatectomy reporting significantly less support than the hormonal therapy group. Conclusion: Future research from both, the providers' and the patients' perspective, will have to clarify if we can interpret our results as change in the communication behaviour once the treatment decision for prostatectomy or hormonal therapy is made.

A review of topical negative pressure therapy in wound healing: Sufficient evidence? (Article)

Mouës, C.M. — 2011-04-01T00:00:00Z

Background Topical negative pressure (TNP) therapy has become a useful adjunct in the management of various types of wounds. However, the TNP system still has characteristics of a "black box" with uncertain efficacy for many users. We extensively examined the effectiveness of TNP therapy reported in research studies. Data sources A database search was undertaken, and over 400 peer-reviewed articles related to the use of TNP therapy (animal, human, and in vitro studies) were identified. Conclusions Almost all encountered studies were related to the use of the commercial VAC device (KCI Medical, United States). Mechanisms of action that can be attributed to TNP therapy are an increase in blood flow, the promotion of angiogenesis, a reduction of wound surface area in certain types of wounds, a modulation of the inhibitory contents in wound fluid, and the induction of cell proliferation. Edema reduction and bacterial clearance, mechanisms that were attributed to TNP therapy, were not proven in basic research.

Fumarates vs. methotrexate in moderate to severe chronic plaque psoriasis: a multicentre prospective randomized controlled clinical trial (Article)

Fallah Arani, S — 2011-04-01T00:00:00Z

Background Methotrexate and fumarates are effective systemic therapies for moderate to severe psoriasis according to the European S3 guidelines. Objectives We conducted a randomized controlled trial comparing the effectiveness and the adverse events of methotrexate and fumarates. Methods Sixty patients with moderate to severe psoriasis vulgaris were randomly assigned to treatment for 16 weeks with either methotrexate (30 patients; 15 mg per week) or fumarates (30 patients; 30 mg, followed by 120 mg according to a standard progressive dosage regimen) and were followed up for 4 weeks. The primary endpoint with respect to the efficacy was the difference in mean change from baseline in Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment. The study was powered to detect a difference of five points. Analyses were by intention to treat. Results Six patients were excluded because five were not eligible and one withdrew consent. Two patients in the methotrexate group and one in the fumarate group dropped out during the 12 weeks of treatment because of nonappearance at the outpatient clinic. In total, 25 patients in the methotrexate group and 26 in the fumarate group were evaluated in the primary analysis. After 12 weeks of treatment, the mean ± SD PASI decreased from 14·5 ± 3·0 at baseline to 6·7 ± 4·5 in the 25 patients treated with methotrexate, whereas it decreased from 18·1 ± 7·0 to 10·5 ± 6·7 in the 26 patients treated with fumarates. After adjustment for baseline values, the absolute difference (fumarates minus methotrexate) in the mean values at 12 weeks was 1·4 (95% confidence interval −2·0 to 4·7; P = 0·417). Conclusions In this randomized trial methotrexate and fumarates were found to be equally effective in the treatment of patients with moderate to severe psoriasis. No serious or irreversible adverse events were observed in any of the patients.

Narrowband ultraviolet B inhibits innate cytosolic double-stranded RNA receptors in psoriatic skin and keratinocytes (Article)

Rácz, E. — 2011-04-01T00:00:00Z

Background: The mode of action of narrowband ultraviolet B (NB-UVB) therapy in clearing psoriasis is incompletely understood, and in vivo studies at the molecular level in patients undergoing NB-UVB therapy are limited. We previously demonstrated increased expression and activity of double-stranded RNA (dsRNA) receptors in psoriasis lesions, and suggested that this enhanced innate signalling contributed to the maintenance of psoriatic inflammation. Objectives: We investigated whether NB-UVB affects dsRNA receptor expression and function in vivo as well as in vitro. Methods: Skin samples of patients with psoriasis undergoing NB-UVB treatment were analysed for epidermal messenger RNA (mRNA) expression of the various dsRNA receptors by microarray and quantitative reverse transcription-polymerase chain reaction. Primary human keratinocytes were irradiated with NB-UVB and stimulated with interferon (IFN)-α or IFN-γ, critical cytokines in psoriasis. The dsRNA analogue polyriboinosinic-polyribocytidylic acid was used to assess the functional responsiveness of the cells to dsRNA. Results: NB-UVB therapy of patients with psoriasis resulted in a significantly reduced mRNA expression of the activating dsRNA receptors MDA5 (IFIH1) and RIG-I (DDX58). On the other hand, expression of LGP2 (DHX58), toll-like receptor 3 (TLR3) and PKR (EIF2AK2) was not affected. In vitro, NB-UVB irradiation completely blocked the upregulation of four of the dsRNA receptors in primary human keratinocytes stimulated with IFN-α or IFN-γ, resulting in an attenuated inflammatory response to dsRNA. Conclusions: Our results show that NB-UVB irradiation inhibits the local innate inflammatory response to dsRNA, and suggest a novel mechanism of action of NB-UVB phototherapy in psoriasis. © 2011 The Author BJD

Acquired scrotal lymphangioma successfully treated using carbon dioxide laser ablation (Article)

Lanjouw, E. — 2011-04-01T00:00:00Z

Methodological pluralism in health communication research (Article)

Neumann, H.A.M. — 2011-03-01T00:00:00Z

Nasal reconstruction after malignant tumor resection: An algorithm for treatment (Article)

Moolenburgh, S.E. — 2011-03-01T00:00:00Z

Validation of self-reported folic acid use in a multiethnic population: results of the Amsterdam Born Children and their Development study (Article)

Sikkens, J.J. — 2011-02-16T00:00:00Z

OBJECTIVE: To assess folic acid supplementation rates and validate the self-reporting of folic acid supplement use among pregnant women in a multiethnic cohort. DESIGN: Secondary analysis of a prospective cohort study. SETTING: Self-reported folic acid supplement use in the Amsterdam Born Children and their Development study cohort was compared with serum folate concentrations using non-parametric trend analysis and linear and logistic regression. SUBJECTS: A total of 4234 pregnant women of various ethnic backgrounds. RESULTS: Serum folate levels showed a significant positive linear trend as reported use of folic acid increased (P < 0·001), which was supported by linear regression (r = 0·49). Odds of having low serum folate concentration decreased with reported early start of folic acid intake. Young, multiparous or non-Western women reported less pre-conception folic acid intake. Non-Western women showed lower serum folate concentrations. The overall rate of over-reporting, i.e. serum folate concentrations ≤20 nmol/l while reporting the use of folic acid supplements, was 20·7 %. Women of Surinamese and Moroccan ancestry had higher odds of over-reporting (OR = 2·3; 95 % CI 1·5, 3·5 and OR = 2·3; 95 % CI 1·3, 4·0, respectively). The odds for Surinamese women remained significant after adjusting for the onset of supplement use, parity and age (OR = 1·7; 95 % CI 1·1, 2·6). CONCLUSIONS: Although self-reporting is a valid method for assessing folic acid supplement use in a multiethnic population, some participants do over-report. Surinamese and possibly Moroccan women appear to over-report more often. Rates of supplementation are low, especially in non-Western women. This suggests the need for intensifying current campaigns or perhaps even additional advice to start or continue to use folic acid post-conceptionally.

IL-1F5, -F6, -F8, and -F9: A novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression (Article)

Johnston, A. — 2011-02-15T00:00:00Z

IL-1F6, IL-1F8, and IL-1F9 and the IL-1R6(RP2) receptor antagonist IL-1F5 constitute a novel IL-1 signaling system that is poorly characterized in skin. To further characterize these cytokines in healthy and inflamed skin, we studied their expression in healthy control, uninvolved psoriasis, and psoriasis plaque skin using quantitative RT-PCR and immunohistochemistry. Expression of IL-1F5, -1F6, -1F8, and -1F9 were increased 2 to 3 orders of magnitude in psoriasis plaque versus uninvolved psoriasis skin, which was supported immunohistologically. Moreover, treatment of psoriasis with etanercept led to significantly decreased IL-1F5, -1F6, -1F8, and -1F9 mRNAs, concomitant with clinical improvement. Similarly increased expression of IL-1F5, -1F6, -1F8, and -1F9 was seen in the involved skin of two mouse models of psoriasis. Suggestive of their importance in inflamed epithelia, IL-1α and TNF-α induced IL-1F5, -1F6, -1F8, and -1F9 transcript expression by normal human keratinocytes. Microarray analysis revealed that these cytokines induce the expression of antimicrobial peptides and matrix metalloproteinases by reconstituted human epidermis. In particular, IL-1F8 increased mRNA expression of human β-defensin (HBD)-2, HBD-3, and CAMP and protein secretion of HBD-2 and HBD-3. Collectively, our data suggest important roles for these novel cytokines in inflammatory skin diseases and identify these peptides as potential targets for antipsoriatic therapies.

Incidence, Prevalence and Future Trends of Primary Basal Cell Carcinoma in the Netherlands (Article)

Flohil, S.C. — 2011-01-24T00:00:00Z

Abstract: Basal cell carcinoma (BCC) incidence rates are increasing worldwide. This study’s objective was to estimate the occurrence of BCC in the Netherlands in terms of incidence and prevalence. Data on first primary carcinomas were retrieved from the Eindhoven Cancer Registry and extrapolated to the Dutch population. Extrapolated data showed a total of 444,131, histologically confirmed cases in the Netherlands between 1973 and 2008. During this period, age-adjusted incidence rates (European Standard Population) increased approximately three-fold from 40 to 148 per 100,000 in males and from 34 to 141 in females. Lifetime risk of BCC was 1 in 5–6 for Dutch citizens. Disease prevalence in the Netherlands was 1.4% and almost four times higher than this (5.4%) in the oldest age group (age 65 years or more). Predictions of future trends showed no signs of a plateau in the number of cases. These estimates should urge Dutch policymakers to provide solutions for the growing group of patients with BCC.

Assessing the public's preference for surgical treatment of primary basal cell carcinoma: A discrete-choice experiment in the South of the Netherlands (Article)

Essers, B.A.B. — 2010-12-01T00:00:00Z

Background Basal cell carcinoma (BCC) is a slowly growing nonmelanoma type of skin cancer that often is located on the face. Different therapies are available to treat BCC, of which surgical excision (SE) and Mohs micrographic surgery (MMS) are the most frequently used surgical procedures. ObjectiveS To examine which attributes of a surgical treatment the general public values as important and to determine the incremental willingness to pay for MMS versus SE. Methods A discrete-choice experiment (DCE) was conducted among members of the general public to examine which attributes of a surgical treatment for primary BCC are valued as important. In addition, based on the attributes included in the experiment, the willingness to pay for MMS versus SE was determined. Results Respondents (N=312) preferred a treatment with a lower recurrence rate, shorter surgery time, shorter travelling time, shorter waiting time, no risk for re-excision, and lower cost. The incremental willingness to pay for MMS was 847 euro ($1,203). Conclusions Results from this DCE indicate that, when outcome and process attributes are considered from a societal perspective, MMS is preferred over SE for primary BCC.

The heat-pipe resembling action of boiling bubbles in endovenous laser ablation (Article)

Geld, C.W.M. van der — 2010-11-01T00:00:00Z

Endovenous laser ablation (EVLA) produces boiling bubbles emerging from pores within the hot fiber tip and traveling over a distal length of about 20 mm before condensing. This evaporation-condensation mechanism makes the vein act like a heat pipe, where very efficient heat transport maintains a constant temperature, the saturation temperature of 100°C, over the volume where these non-condensing bubbles exist. During EVLA the above-mentioned observations indicate that a venous cylindrical volume with a length of about 20 mm is kept at 100°C. Pullback velocities of a few mm/s then cause at least the upper part of the treated vein wall to remain close to 100°C for a time sufficient to cause irreversible injury. In conclusion, we propose that the mechanism of action of boiling bubbles during EVLA is an efficient heat-pipe resembling way of heating of the vein wall.