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W Bergman

Publications and source records attributed to W Bergman.

At least 37 records · Page 2Linked to original sources
PubMed1999

Familial melanoma; CDKN2A and beyond.

The most common hereditary melanoma susceptibility disorder is the familial atypical multiple mole-melanoma (FAMMM) syndrome. FAMMM is regarded as an ideal natural model to study the very complex pathologic mechanism of melanoma. In 1994, cloning of the melanoma susceptibility gene CDKN2A was thought to give answers to many questions on genotype-phenotype correlations in familial melanoma. Today, 4 y later, germline mutations cosegregate with melanoma in only 40%-50% of the families predisposed to this disease. The hunt for genes and modifying genes is on again. Through the years the very well-characterized Dutch FAMMM families have proven to be valuable study subjects in melanoma research. This paper describes over 10 y of melanoma research illustrated by research performed in the Dutch FAMMM families.

Chromosomes, Human, Pair 9↗
PubMed1999

Consensus on the management of malignant melanoma of the skin in The Netherlands. Dutch Melanoma Working Party.

In 1996 the Dutch Melanoma Working Party, in co-operation with the National Organization for Quality Assurance in Hospitals in the Netherlands and the Dutch Association of Comprehensive Cancer Centres, organized the third consensus conference on the management of melanoma of the skin. The following guidelines were approved. The recommended margin for diagnostic excision is 2 mm of macroscopically normal skin around the lesion; the margins for therapeutic excision are 1 cm of normal skin for a Breslow thickness of < or = 2 mm and 2 cm for a Breslow thickness of > 2 and < or = 4 mm. A margin of at least 2 cm also appears to be justified for thicker melanomas. Elective lymph node dissection is not recommended. Sentinel node biopsy appears to be a promising method to detect occult metastases in the regional lymph nodes. If regional lymph node metastases are present, therapeutic regional lymph node dissection must be conducted. Isolated regional perfusion is indicated for inoperable tumour growth in an extremity. Radiotherapy can be applied curatively (for example, if surgery is not possible), palliatively (if desired in combination with hyperthermia) or postoperatively (if non-radical resection is suspected). Adjuvant systemic therapy for melanoma patients is still experimental. Atypical (dysplastic) naevi and congenital naevi are major risk factors for melanoma. No consensus has been reached about the prophylactic excision of all congenital naevi. A follow-up period of 5 years is sufficient for patients with a melanoma of < or = 1.5 mm Breslow thickness (provided there are no histological signs of regression) and of 10 years when the Breslow thickness is > 1.5 mm. The patient should be actively involved in the follow-up (inspection, palpation). Regular routine blood tests, radiological examination and ultrasound scanning are not considered to be worthwhile. There is no evidence that the growth of micro-metastases is stimulated by hormonal changes during pregnancy or contraceptive pill use. Excessive exposure to ultraviolet radiation should be discouraged. Regular population screening for melanoma is not considered to be worthwhile, owing to the relatively low frequency and the predominantly favourable stage at the time of diagnosis, particularly in young people.

Diagnosis↗
PubMed1999

A locus linked to p16 modifies melanoma risk in Dutch familial atypical multiple mole melanoma (FAMMM) syndrome families.

The CDKN2A gene that encodes the cell cycle inhibitor p16 shows mutations in many but not all 9p21-linked melanoma families. Most Dutch melanoma families segregate for a unique founder mutation (p16-Leiden), encoding a truncated nonfunctional p16 protein. The highly variable risk for p16-Leiden carriers to develop melanoma suggests a role for other genetic and/or environmental factors. We hypothesized that a 9p21 gene other than CDKN2A may be relevant in the remaining 9p21-linked melanoma families without p16 mutations but may also act as a risk modifier in p16-Leiden carriers. Haplotype analysis for 9p21 was performed using microsatellite markers in six p16-Leiden families originating from a founder population. p16-Leiden carriers in two families shared an unexpectedly large founder haplotype ( approximately 20-cM) around CDKN2A, mostly in proximal direction. Melanoma-positive p16-Leiden carriers from these families showed this extensive proximal haplotype compared with melanoma-negative p16-Leiden carriers from the same families. Additional p16-Leiden families less heavily affected with melanoma showed shorter haplotypes sharing, excluding the region proximally of CDKN2A. The presence of a gene involved in melanoma susceptibility proximal of CDKN2A is corroborated by somatic deletions of 9p in tumors, which frequently do not include CDKN2A but a more proximal chromosomal area instead. Our results provide a candidate region for further gene mapping in p16-negative 9p21-linked melanoma families and guide the search for risk modifiers in melanoma development.

Alleles↗
PubMed1998

Illness perceptions, coping and functioning in patients with rheumatoid arthritis, chronic obstructive pulmonary disease and psoriasis.

The present cross-sectional study analyzed the extent to which illness perceptions and coping strategies (as measured by the Illness Perception Questionnaire and the Utrecht Coping List, respectively) are associated with levels of daily functioning, as indicated by the Medical Outcomes Study SF-20, and disease-specific measures in 244 adults: 84 with rheumatoid arthritis (RA); 80 with chronic obstructive lung disease (COPD); and 80 with psoriasis. The results of stepwise regression analyses indicated that a strong illness identity, passive coping, belief in a long illness duration, belief in more severe consequences, and an unfavorable score on medical variables were associated with worse outcome on disease-specific measures of functioning and on general role and social functioning. Coping by seeking social support and beliefs in controllability/curability of the disease were significantly related to better functioning. The implications of these findings for future interventions and research are discussed.

Activities of Daily Living↗
PubMed1998

Excess cancer mortality in six Dutch pedigrees with the familial atypical multiple mole-melanoma syndrome from 1830 to 1994.

An increased incidence of systemic cancers has been described in some reports of familial atypical multiple mole-melanoma kindreds. If the gene defect underlying the familial atypical multiple mole-melanoma syndrome is not only important for the development of melanoma of the skin, the impact of the defect on life expectancy may be much higher than previously thought. We investigated all-cause mortality from 1830 to the present and causes of death from 1941 to 1994 in proven, obligate, and potential CDKN2 mutation carriers to obtain an estimate of the impact of a hereditary defect of the CDKN2 gene on mortality. From 1830 to 1994 there were 65 deaths, although only 42 deaths were expected [standardized mortality ratio (SMR) 1.6, 95% confidence interval (CI) 1.2-2.0] and the SMR doubled with calendar time. Excess mortality was shown in most of the families, but was confined to ages 35-70 y (SMR 2.1, 95%CI 1.5-2.9). Excess mortality could be fully attributed to cancer mortality, especially to pancreatic carcinoma and melanoma of the skin. There appeared to be some heterogeneity among the families, especially due to the specific cancer pattern within a family. The impact of the defect of the CDKN2 gene is rising over calendar time, mainly because the mortality in the general population has been falling. Excess mortality was not only due to melanoma, but also to pancreatic carcinoma. Therefore, follow-up programs of affected family members should not be confined to a regular check of the atypical nevi.

Adult↗
PubMed1998

Multiple agminate Spitz naevi.

We report two patients with multiple agminate Spitz naevi (MASM), a rare disorder. In case 1, a 16-year-old girl, the results of chromosomal investigation of fibroblasts from the affected area (translocation 45, X, t(4; 7) (p14; p22) in a mosaic pattern) suggest that early during embryogenesis a de novo reciprocal translocation has occurred between chromosomes 4 and 7. This resulted in the skin lesions as described on the right shoulder, arm and hand. The melanoma risk in MASM is also discussed.

Adolescent↗
PubMed1998

Occurrence of cutaneous and uveal melanoma in patients with uveal melanoma and their first degree relatives.

Uveal and cutaneous melanomas are rare tumours, but have been described to occur together in one patient or in members of the same family. A group of 109 consecutive uveal melanoma patients from one specialized ocular tumour clinic were investigated dermatologically. The patient's own history and medical data and the family history of skin or eye problems were recorded. A total of three cutaneous melanomas were found as a result of this study--two in ocular melanoma patients and one in a first-degree relative. Four patients had first-degree relatives with a skin melanoma (in three of these families dysplastic naevus syndrome was also found), and one patient had a first-degree relative with an uveal melanoma. To find cutaneous and uveal melanoma coexisting in two cases and cutaneous melanoma in first-degree relatives in four cases out of a total of 109 uveal melanoma patients seems more than a coincidence. A linking factor in three cases was the familial atypical multiple mole melanoma syndrome, suggesting a common genetic predisposition to both malignancies in these families. In our only family with familial uveal melanoma, cutaneous melanoma and atypical naevi did not occur. A different genetic mechanism for these cases is probable.

Aged↗
PubMed1998

Effect of topical tretinoin under occlusion on atypical naevi.

Atypical naevi are potential precursors of melanoma and markers of increased melanoma risk. To examine the possibility of chemoprevention of melanoma by retinoids, we studied the effect of topical tretinoin 0.1% (all-transretinoic acid; vitamin A acid) and tretinoin 0.1% with hydrocortisone on atypical naevi. Thirty patients with atypical naevi were enrolled in a prospective randomized double blind study. For each patient three comparable naevi were selected and randomized to receive tretinoin 0.1% (T), tretinoin 0.1% with hydrocortisone 1% (C) or a placebo cream (P) once a week under Actiderm occlusion for 4 months. Baseline views of the naevi, taken with a videomicroscope (magnification 20 x), were assessed for morphological changes compared with views taken 2 months after the beginning of treatment, 1 week after completion of treatment and 6 months later. After completion of the study all naevi in the T and C groups and six naevi in the P group were removed and evaluated histologically for the presence of atypia. The number of naevi that had changed in colour or size was significantly higher in the T and C groups compared with the placebo group. A size reduction took place in 42.9% (T) and 40.0% (C) of the naevi and the colour changed in 75.0% (T) and 66.7% (C). The effect of treatment, in general subtle, did not differ significantly between groups T and C, but naevi treated with C became significantly less irritated. Histologically, 75.0% of the naevi treated with T and 69.6% of the naevi treated with C were atypical. Therefore, no major change was seen in the clinical aspect of atypical naevi after treatment with tretinoin 0.1% or tretinoin with hydrocortisone 1%, and most of the treated naevi still met the histological criteria for atypia after the treatment period. The current management of follow-up of atypical naevi and excision when change to melanoma is suspected is therefore still recommended. Nevertheless, some response was seen, which may justify a further exploration of tretinoin and hydrocortisone 1% therapy for a longer treatment period in combination with research to clarify its mechanism.

Adult↗
PubMed1998

Genetics of familial atypical multiple mole-melanoma (FAMMM) syndrome in The Netherlands: how far have we come?

By the genetic localization of the first melanoma susceptibility gene on chromosome 1p we thought that the puzzle on familial melanoma families would soon be solved. Now, almost fifteen years later we have learned that inherited melanoma is not a simple genetic disorder and that multiple genes, modifying genes and environmental factors might be involved. This paper outlines the current understanding of the genetics of melanoma and the relationship to atypical nevi based on more than ten years of genetic analysis in the Dutch familial atypical multiple mole-melanoma (FAMMM) syndrome families.

Chromosomes, Human, Pair 1↗
PubMed1997

[Dysplastic nevi and the risk of melanoma: a guideline for patient care. Nederlandse Melanoom Werkgroep van de Vereniging voor Integrale Kankercentra].

Consensus was recently reached in the Netherlands regarding the clinical management of dysplastic naevi and the definitions in clinical and pathological diagnostics. The term 'dysplastic' is reserved for histological diagnostics; the term preferred for clinical use is 'clinically atypical naevus'. A naevus is defined as clinically atypical if it meets three of the following five criteria: > or = 5 mm in diameter, vaguely bordered, asymmetrically shaped, irregularly pigmented and a red hue (erythema). Presence of clinically atypical naevi is a main risk factor for melanoma. Dysplastic naevus syndrome (DNS) is present if a patient has a melanoma and one or several clinically atypical naevi. The diagnosis of 'familial DNS' (familial atypical multiple mole-melanoma syndrome, abbreviation FAMMM syndrome) is made if at least two close relatives (including the patient) are known with a melanoma with or without atypical naevi, while one or several (other) relatives have atypical naevi. The risk of melanoma in a gene carrier of familial DNS is close to 100%, while multiple melanomas develop in 30% of the gene carriers. No DNA diagnostics is yet possible in most DNS/FAMMM families, because of the involvement of genes yet unknown. Accordingly, at present it is still too early for DNA diagnostics. Currently, therefore, the diagnosis is based only on anamnestic, clinical and histological grounds.

Clinical Protocols↗
PubMed1997

[2nd revised consensus skin melanoma. De Nederlandse Melanoom Werkgroep].

The 'Guideline melanoma of the skin, second revised consensus' was published in March 1997. Some of the contents are cited: Over 1600 new melanomas are diagnosed in the Netherlands each year; by now the mean 5-year survival amounts to over 80%. In examination of a pigmented lesion a dermatoscope is a valuable tool. The recommended margin of the diagnostic excision was reduced from 5 mm to 2 mm of macroscopically normal skin round the lesion; the margins in definite excision are: 1 cm of normal skin for a Breslow thickness < or = 2 mm; 2 cm for a Breslow thickness > 2 and < or = 4 mm. A margin of at least 2 cm seems also justified for thicker melanomas. Elective (prophylactic) regional lymph node dissection is advised against. Sentinel node biopsy appears to be an attractive method to detect occult metastasis in regional nodes. In lymph node metastasis a (therapeutic) regional lymph node dissection should be performed. In case of inoperable tumourgrowth in an extremity regional isolated perfusion is indicated. Radiotherapy may be applied curatively (e.g. if surgery is not possible), palliatively (if desired in combination with hyperthermia) or postoperatively (if non-radical resection is suspected). Adjuvant systemic therapy in melanoma patients is still experimental; the earliest results of high doses of interferon alpha are encouraging. Atypical (dysplastic) naevi and congenital naevi are important risk factors for melanoma. No consensus was reached regarding prophylactic removal of all congenital naevi. Regarding the duration of the follow-up period, 5 years suffices in patients with a melanoma with a Breslow thickness < or = 1.5 mm (provided there are no histological signs of regression), while 10 years is required for melanomas with a Breslow thickness > 1.5 mm. The patient should be actively involved in the follow-up (inspection, palpation). Routine blood testing, roentgen examination or ultrasonography are considered to be useless. There are no indications that hormonal alterations during pregnancy or use of the pill stimulate the growth of micrometastases that may be present. Excessive exposure to ultraviolet rays is discouraged.

Biopsy↗
PubMed1997

Ultraviolet exposure and the development of banal and atypical naevi--a cross-sectional study on Curaçao and in The Netherlands.

The atypical naevus is both a risk factor for and a precursor lesion of melanoma. Sunlight is known to be an important aetiological factor for melanoma. Whether solar exposure is also involved in the initiation of (atypical) naevi is an issue of current interest. We performed a cross-sectional study among 270 inhabitants in the cloudy Netherlands and 282 white Dutch immigrants of the tropical island Curaçao to investigate whether solar exposure plays a role in the development of atypical naevi. All participants were interviewed and underwent total skin examination; banal melanocytic naevi and atypical naevi were counted. There was no significant difference in the mean number of melanocytic naevi > or = 2 mm or > or = 5 mm between Curaçao and the Netherlands. Furthermore, there was no significant difference in the mean crude and age standardized prevalence of atypical naevi between the Netherlands and Curaçao. In both groups individuals with atypical naevi had significantly more total naevi. Concerning the role of sun exposure in the development of naevi in the Netherlands, we found that the total naevus count had a significant association with cumulative sun exposure before the age of 12 as well as with two or more painful sunburns before the age of 12. In Curaçao these relationships were not observed. In contrast, however, on Curaçao the presence of atypical naevi showed an association (odds ratio = 2.6, 95% confidence interval 1.1-6.0) with the highest level of cumulative sun exposure and with painful sunburns before the age of 12 (odds ratio = 2.6, 95% confidence interval 1.2-5.5). In the Dutch group these associations were not significant. We hypothesize that in the development of banal naevi there is an association between the total number of naevi and sun exposure only at low exposure levels; however, after overstepping a critical threshold a further association between melanocytic naevi and sun exposure is lacking. Sunlight exposure before the age of 12 plays a complex role: only very high exposure levels seem to contribute to the development of atypical naevi.

Adolescent↗
PubMed1997

What do children aged 5 to 11 years old know about the sun and skin cancer? The practical difficulties of international collaborative research when analysis of language is involved.

The objective of this study was to determine the perceptions of primary school children about sun exposure and skin cancer, and the language they use about these issues, as a basis for the design of health promotional materials. In all, 2857 children in five European countries took part in the study and were compared with 641 Australian children participating in a similar study, since the latter have been exposed to more intensive health education about the sun. The 'draw and write' technique was used. In Europe the level of awareness about the risks of excessive sun exposure and the need to protect the skin was considerably lower than in Australia, although there was some variation within northern Europe. Amongst the European children acknowledging a need to protect the skin, the principal means of protection quoted was the use of suncreams, with inadequate awareness of the value of clothing, hats and shade. European children expressed greater approval of suntans than did the Australian children. Some methodological problems were encountered as a result of nuances in the languages involved, emphasizing difficulties in international research of this type.

Age Factors↗
PubMed1996

Chronic sun exposure and age are inversely associated with nevi in adult renal transplant recipients.

In 126 adult renal transplant recipients who had survived their transplantation for at least 8 years, we determined whether numbers of nevi and the presence of clinically atypical nevi were related to chronic sun exposure. On the basis of a skin examination, three groups were defined: patients with at least one clinically a typical nevus; patients with only clinically normal nevi: and patients without any nevi. The prevalence odds ratio of having any clinically atypical nevi as compared to having only clinically normal nevi was calculated in a logistic model, in relation to gender, skin type, age, sun exposure, and number of keratotic skin lesions present. Similarly, the prevalence odds ratio of having 30 or more nevi compared to fewer than 30 nevi was calculated. We found an inverse association between chronic sun exposure and age with numbers of nevi in adult renal transplant recipients. The presence of clinically atypical nevi was also inversely associated with chronic sun exposure, but this association disappeared after adjustment for age. We did not observe an association of nevi with the number of keratotic skin lesions, nor with humoral immune responses against human papillomavirus and the presence of certain HLA antigens, which are factors associated with nonmelanoma skin cancer in renal transplant recipients. Chronic sun exposure and age appeared to be strong determinants for decreased numbers of nevi in adult renal transplant recipients. Infection with human papillomaviruses does not appear to play an important role.

Adult↗
PubMed1995

Homozygotes for CDKN2 (p16) germline mutation in Dutch familial melanoma kindreds.

The p16 gene (CDKN2) which is localized on chromosome 9p21, is deleted in a significant number of sporadic cancers. Moreover, germline mutations identified in some melanoma-prone kindreds last year suggested that CDKN2 is identical to the 9p21-linked melanoma susceptibility gene (MLM); however, failure to identify p16 mutations in all melanoma kindreds putatively linked to 9p21 left some doubts. We have analysed CDKN2 coding sequences in 15 Dutch familial atypical multiple mole-melanoma (FAMMM) syndrome pedigrees, and identified a 19 basepair (bp) germline deletion in 13 of them. All 13 families originate from an endogamous population. The deletion causes a reading frame shift, predicted to result in a severely truncated p16 protein. Interestingly, two family members are homozygous for the deletion, one of whom shows no obvious signs of disease. This surprising finding demonstrates that homozygotes for this CDKN2 mutation are viable, and suggests the presence of a genetic mechanism that can compensate for the functional loss of p16. Our results also greatly strengthen the notion that p16 is indeed MLM.

Amino Acid Sequence↗
PubMed1995

A comparative study of atypical and melanocytic naevi on the tropical island Curaçao and in The Netherlands.

A cross-sectional study was undertaken in 270 inhabitants of The Netherlands (moderate maritime climate, latitude 51 degrees 5' N-53 degrees 3' N) with skin types I-III and 757 inhabitants of the tropical island Curaçao (latitude 12 degrees 2' N-12 degrees 23' N). The latter group consisted of 282 White individuals (mostly Dutch immigrants) and 475 people with non-White skin types IV, V and VI. All participants underwent total skin examination and melanocytic naevi (MN) and clinically atypical naevi (AN) were noted. There was no statistical difference in the mean number of naevi > or = 2 mm or > or = 5 mm between the Curaçao and The Netherlands White groups, but the mean number of naevi > or = 2 mm and > or = 5 mm was significantly lower in the Curaçao non-White group. We found no obvious differences in mean naevus counts between genders and the various comparable age groups. Furthermore, we found no significant difference in mean crude and mean age-standardized prevalence of (one or more) AN between Whites in The Netherlands and on Curaçao. The Mantel-Haenszel prevalence ratio weighted for age and gender differences of Curaçao Whites vs non-Whites was 5.93 (95% confidence interval 3.9-12.0), demonstrating that AN are significantly less prevalent in darker skin types. In all groups, people with AN had significantly more MN than people without AN. We found a generation-dependent difference in the expression of AN among White inhabitants of The Netherlands and on Curaçao, with a higher prevalence of AN in the younger generation.

Adolescent↗