Clinical Characteristics of Cutaneous Melanoma and Second Primary Malignancies in a Dutch Hospital-Based Cohort of Cutaneous Melanoma Patients

The increasing number of living cutaneous melanoma patients and the increased risk of developing a second primary tumour incited us to analyse the clinical characteristics of cutaneous melanoma and define the frequency, site, and type of second primary cancers in cutaneous melanoma patients. We collected data on patients who visited the Department of Dermatology at the Radboud University Nijmegen Medical Centre and were newly diagnosed with cutaneous melanoma or metastasis of melanoma with unknown primary localization between 2002 and 2006. A total of 194 cases were included; eleven patients developed a subsequent melanoma, 24 had at least one basal cell carcinoma, three had at least one squamous cell carcinoma, and 21 patients had a second non-cutaneous primary malignancy. In conclusion, 48 patients developed a subsequent malignancy. As nonmelanoma skin cancer is the most frequent second malignancy, our results subscribe to the necessity of follow-up by a dermatologist

The lymphoid chemokine CCL21 triggers LFA-1 adhesive properties on human dendritic cells

Item does not contain fulltextDendritic cells (DCs) are the most potent APCs, involved in the induction of immunity and tolerance. Recently we showed that during differentiation of human DCs from monocyte precursors, Lymphocyte function-associated antigen-1 (LFA-1)-binding capacity is lost, although integrin expression levels were maintained constant, suggesting a different regulation mechanism of this integrin on different cell types. However, the exact role of LFA-1 in DC adhesion and migration remains obscure. Chemokines are potent regulators of integrin function, influencing migratory and adhesive properties of leukocytes. Here, we show that upon vaccination of cancer patients with human DCs, cells that have migrated in vivo into the lymph nodes upregulated the active form of LFA-1. We further show that exposure of human DCs to the lymphoid chemokine CCL21 specifically restores the high-affinity form of LFA-1 and induces binding to its ligand ICAM-1 under low shear stress. Our data indicate that on DCs LFA-1 may function as an inducible anchor during lymphatic transmigration or within the lymph nodes. A thorough understanding of the adhesive events during the DC life cycle will help to improve the outcome of DC-based antitumor clinical trials

Proposal to extend the PROMIS® item bank v2.0 ‘Ability to Participate in Social Roles and Activities’: item generation and content validity

Purpose: Previous research indicated that the Patient-Reported Outcomes Measurement Information System (PROMIS®) item bank v2.0 ‘Ability to Participate in Social Roles and Activities’ may miss subdomains of social participation. The purpose of this study was to generate items for these missing subdomains and to evaluate their content validity. Methods: A three-step approach was followed: (1) Item generation for 16 International Classification of Functioning Disability and Health subdomains currently not covered by the item bank; (2) Evaluation of content validity of generated items through expert review (n = 20) and think-aloud interviews with a purposeful sample of people with and without (chronic) health conditions (n = 10), to assess item comprehensibility, relevance, and comprehensiveness; and 3) Item revision based on the results of step 2, in a consensus procedure. Results: First, 48 items were generated. Second, overall, content experts indicated that the generated items were relevant. Furthermore, based on experts’ responses, items were simplified and ‘participation in social media’ was identified as an important additional subdomain of social participation. Additionally, ‘participating in various social roles simultaneously’ was identified as a missing item. Based on the responses of the interviewed adults items were simplified. Third, in total 17 items, covering 17 subdomains, were proposed to be added to the original item bank. Discussion: The relevance, comprehensibility and comprehensiveness of the 17 proposed items were supported. Whether the proposed extension of the item bank leads to better psychometric properties of the item bank should be tested in a large-scale field study

A qualitative study investigating the meaning of participation to improve the measurement of this construct

Purpose: The purpose of this study was to improve the measurement of participation. Research questions were as follows: (1) What constitutes participation according to adults? (2) Do they mention participation subdomains that are not covered in the Patient-Reported Outcomes Measurement Information System (PROMIS) item bank “Ability to Participate in Social Roles and Activities”? Methods: Semi-structured interviews were conducted with 46 adults from the general population. Interviews were thematically analysed using the International Classification of Functioning, Disability and Health (ICF) as conceptual framework. Thereafter, assigned codes were compared to PROMIS item bank. Results: Participants mentioned a variety of participation subdomains that were meaningful to them, such as socializing and employment. All subdomains could be classified into the ICF. The following subdomains were not covered by the PROMIS item bank: acquisition of necessities, education life, economic life, community life, and religion and spirituality. Also a distinction between remunerative (i.e. paid) and non-remunerative (i.e. unpaid) employment, and domestic life was missing. Several ICF sub-codes were not mentioned, such as ceremonies. Conclusions: Many participation subdomains were mentioned to be meaningful. As several of these subdomains are not covered in the PROMIS item bank, it may benefit from extension with new (patient-)reported subdomains of participation

High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia.

Item does not contain fulltextIn acute myeloid leukemia (AML), aberrant expression and mutations of transcription factors have been correlated with disease outcome. In the present study, we performed expression and mutation screening of GATA2, which is an essential transcription factor for regulation of myeloid lineage determination, in de novo pediatric AML patients. GATA2 mutations were detected in 5 of 230 patients, representing a frequency of 2.2% overall and 9.8% in cytogenetically normal AML. GATA2 expression analysis demonstrated that in 155 of 237 diagnostic samples (65%), GATA2 expression was higher than in normal BM. In complete remission, normalization of GATA2 expression was observed, whereas GATA2 expression levels stayed high in patients with resistant disease. High GATA2 expression at diagnosis was an independent poor prognostic factor for overall survival (hazard ratio [HR] = 1.7, P = .045), event-free survival (HR = 2.1, P = .002), and disease-free survival (HR = 2.3, P = .004). The prognostic impact of GATA2 was particularly evident in specific AML subgroups. In patients with French-American-British M5 morphology, inv(16), or high WT1 expression, significant differences in survival were observed between patients with high versus normal GATA2 expression. We conclude that high GATA2 expression is a novel poor prognostic marker in pediatric AML, which may contribute to better risk-group stratification and risk-adapted therapy in the future

In vivo MR tracking of magnetically labeled cells: first clinical experience with dendritic cell vaccines in melanoma patients.

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