Ingrid Synnerstad

Effect of Pregnancy on Survival in Women With Cutaneous Malignant Melanoma

PURPOSE An adverse influence of pregnancy on the risk of death in women with cutaneous melanoma was suggested historically by anecdotal reports. Previous studies included small numbers of women observed for short periods. METHODS Using data from the Swedish National and Regional Registries, we performed a retrospective cohort study of all Swedish women who were diagnosed with cutaneous melanoma during their reproductive period, from January 1, 1958, to December 31, 1999. The relationship between pregnancy status at the diagnosis of melanoma and overall survival was examined in multivariable proportional-hazards models. RESULTS The cohort comprised 185 women (3.3%) diagnosed with melanoma during pregnancy and 5,348 (96.7%) women of the same childbearing age diagnosed with melanoma while not pregnant. There was no statistically significant difference in overall survival between pregnant and nonpregnant groups (log-rank chi(2)1[r] = 0.84, P = .361). Pregnancy status at the time of diagnosis of melanoma was not related to survival in a multivariable Cox model in the 2,101 women (hazard ratio for death in the pregnant group was 1.08; 95% CI, 0.60 to 1.93). In the multivariable analysis, pregnancy status after diagnosis of melanoma was not a significant predictor of survival (hazard ratio for death in women who had pregnancy subsequent to the diagnosis of melanoma was 0.58; 95% CI, 0.32 to 1.05). CONCLUSION The survival of pregnant women with melanoma is not worse than the survival of nonpregnant women with melanoma. Pregnancy subsequent to the diagnosis of primary melanoma was not associated with an increased risk of death.

Important factors for pain during photodynamic therapy for actinic keratosis

Photodynamic therapy (PDT) is an efficient treatment for actinic keratosis. A common problem, however, is pain. The aim of this study was to investigate pain during PDT for actinic keratosis. The possibility of using capsaicin cream for pain relief was also assessed. Pain was investigated during aminolaevulinic acid PDT in 91 patients. Size, redness, scaling and induration of the lesions were recorded. Maximum pain during treatment was registered, using a visual analogue scale (0-10). The pain-reducing efficacy of capsaicin was tested in a pilot study in six patients (10 lesions). These patients were pre-treated with capsaicin cream for one week before commencing PDT. Pain was found to be normally distributed around a mean value of visual analogue scale 4.6. Larger lesions gave more pain (p=0.001). The redness of the actinic lesions was found to be related to PDT-induced pain (p=0.01), the reduction of actinic area (p=0.007), and the cure rate (p=0.01). The redder the actinic area, the better the treatment outcome and the more pain experienced. Patients with the largest reduction in the actinic area experienced more pain (p=0.053). The most important factors for presence of pain seem to be the size and the redness of the lesion. No significant pain relief was experienced after pre-treatment with capsaicin.

Societal Cost of Skin Cancer in Sweden in 2005

Skin cancer is one of the most rapidly increasing cancers among the Swedish population and a significant cause of illness and death. This study aims to estimate the total societal cost of skin cancer in Sweden for 2005, using a prevalence-based cost-of-illness approach. The total cost of skin cancer was estimated at euro 142.4 million (euro 15/inhabitant), of which euro 79.6 million (euro 8/inhabitant) was spent on health services and euro 62.8 million (euro 7/inhabitant) was due to loss of production. The main cost driver was resource utilization in outpatient care, amounting to 42.2% of the total cost. Melanoma was the most costly skin cancer diagnosis. Non-melanoma skin cancer was, however, the main cost driver for health services alone. For the future it is important to establish effective preventive measures to avoid increasing costs and suffering caused by skin cancer.

Inflammasome polymorphisms confer susceptibility to sporadic malignant melanoma

Genetic variants of NLRP3 and NLRP1 are known to modulate levels of pro‐inflammatory cytokine interleukin (IL)‐1β. The purpose of this study was to investigate the association of NLRP3/NLRP1 polymorphisms with susceptibility and clinical features of malignant melanoma in a Swedish case–control study. Common variants in NLRP3/NLRP1 were investigated in sporadic malignant melanoma patients and healthy controls followed by analysis using logistic regression. NLRP3 variant (rs35829419) was significantly more common in male patients than in controls (OR, 2.22; CI, 1.27–3.86). Upon stratification, significant association with nodular melanoma was observed (OR, 2.89; CI, 1.33–6.30), which intensified in male patients (OR 4.03, CI 1.40–11.59). The NLRP1 variant (rs12150220) was significantly more common in fair‐skinned female patients (OR, 1.85; CI, 1.04–3.33) and showed strong associations with nodular melanoma (OR, 6.03; CI, 1.33–25). Our data suggest that NLRP3/NLRP1 polymorphisms are associated with melanoma susceptibility; these findings warrant validation in other independent populations.

Frequency and distribution pattern of melanocytic naevi in Swedish 8-9-year-old children.

The naevus profile was examined in a Swedish cohort of 8-9-year-old children; 524/545 individuals (96%) were examined (279 boys and 245 girls). There was a wide variation in the total number of naevi (0-79) and boys had more naevi than girls (median 9 and 7, respectively, p<0.01). No dysplastic naevi were found. Overall, 15/ 524 (3%) had at least one lesion clinically diagnosed as a congenital melanocytic naevus. Boys had more naevi on the face (median 1) and trunk (median 5) than girls (median 0 and 3, respectively, p<0.001). There was no difference in the number of naevi on the legs between the two sexes. The highest counts per unit surface area for both sexes were found on the back, chest and the lateral aspect of the arms, areas intermittently sun-exposed. Children with fair skin and light eye colours had significantly more naevi than those with darker colours but children with red hair had very few naevi. Children with one or more naevi on the buttocks (25%), dorsal surfaces of the feet (11%) or on the scalp (7%) had twice as many naevi in total compared with those without naevi in these regions. Children with naevi in all three regions (0.8%) had four times as many naevi in total. A relationship between total counts and counts on the back or lateral aspect of the arms was found (r2 = 0.59). Either of these two areas might be suitable for predicting total naevus counts.

Monitoring of Kindreds With Hereditary Predisposition for Cutaneous Melanoma and Dysplastic Nevus Syndrome: Results of a Swedish Preventive Program

PURPOSE To evaluate a program initiated in 1987 by the Swedish Melanoma Study Group aiming to provide preventive surveillance to kindreds with hereditary cutaneous melanoma and dysplastic nevus syndrome. PATIENTS AND METHODS Overall, 2,080 individuals belonging to 280 melanoma families were followed for 14 years between 1987 and 2001 at 12 participating centers. Data were registered in a central database. RESULTS Among 1,912 skin lesions excised during follow-up, 41 melanomas were removed in 32 individuals. Of these, 15 (37%) were in situ melanomas and 26 (63%) invasive melanomas. The median tumor thickness of invasive melanomas was 0.5 mm. Ulceration was absent in 24 of 26 invasive melanomas (92%) and 12 (46%) lacked vertical growth phase. Compared with melanomas in the general Swedish population, the melanomas identified in these kindreds during follow-up had better prognostic characteristics. All melanomas except one were diagnosed in families with two or more first-degree relatives with melanoma. Diagnosis of melanoma occurred in three of eight kindreds with germline CDKN2A mutations, supporting that families with such mutations are at increased risk for melanoma development. Of the 32 individuals who developed melanoma during follow-up, 21 (66%) had had at least one previously diagnosed melanoma. CONCLUSION This study shows that a coordinated program aimed at detecting and offering skin surveillance in kindreds with hereditary cutaneous melanoma results in a low incidence of melanomas during the follow-up period and that the tumors that do arise have favorable prognostic characteristics.

Frequency and distribution pattern of melanocytic naevi in Estonian children and the influence of atopic dermatitis

Background  There is a strong correlation between naevus number and prospective melanoma risk. Melanoma is one of the most rapidly increasing cancers in Estonia and primary prevention programmes for melanoma that target risk behaviour in the sun have so far not been launched.

Importance of FAS-1377, FAS-670, and FASL-844 polymorphisms in tumor onset, progression, and pigment phenotypes of Swedish patients with melanoma : a case-control analysis.

Purpose:Human skin melanoma at later stages usually has an extremely poor prognosis. It is of importance to search for biologic markers to identify and monitor individuals at risk for melanoma for early diagnosis and to avoid tumor progression. The FAS gene and its natural ligand (FASL) gene initiate the death signal cascade, playing a central role in the apoptotic signaling pathway and tumor growth and metastasis. Patients and Methods:In this study, we analyzed polymorphisms in 229 patients with melanoma and 351 age- and gender-matched tumor-free individuals. Genomic DNAs were isolated from mononuclear cells in peripheral vein blood, and the polymorphisms were examined with polymerase chain reaction–restriction fragment length polymorphism techniques. Frequency in distribution of the polymorphisms was compared between the patients with melanoma and the healthy control subjects, and associations with patients’ pigment phenotypes, age at diagnosis, and melanoma characteristics were analyzed. Results and Conclusions:The FAS-1377, FAS-670, and FASL-844 polymorphisms were not found to be markers of melanoma risk (P > 0.05). In patients with melanoma, frequencies of the FAS-1377, FAS-670, and FASL-844 polymorphisms were different between the patients aged <50 and ≥50 years (P ≤ 0.025, P ≤ 0.025, and P ≤ 0.01). Moreover, the FAS-670 polymorphism correlated with tumor Breslow thickness (P ≤ 0.01) and Clark level (P ≤ 0.001) and was associated with tumors developing in sun-exposed locations (P ≤ 0.001). FAS and FASL were not markers for melanoma risk but might be important in the development and progression of sun-induced melanoma independently of skin type.

Low risk of melanoma in patients with atopic dermatitis

Background  There is a possible association between atopy and cancer based on the concept of atopic diseases as a hyper‐reactive state of the immune system. Melanoma is an immunogenic tumour, and since patients with atopic dermatitis (AD) are subjected to local and systemic immunosuppressives, it would be expected to find an influence of AD on the melanoma risk. There is a positive correlation between the number of naevi and melanoma risk, and children and adults with AD have fewer naevi than controls although many patients receive ultraviolet treatment.

Spectrophotometric Analysis of Melanocytic Naevi During Pregnancy

Malignant melanoma is the most common cancer during pregnancy, but it is unknown whether melanocytic naevi in general are activated. A total of 381 melanocytic naevi in 34 Caucasian primigravidae were examined using spectrophotometric intracutaneous analysis (SIAscopy) technology in early pregnancy and prior to delivery. The Siagraphs of each naevus were then compared in order to evaluate changes over time. A total of 163 melanocytic naevi in 21 nulliparous women served as an additional control group. At the first visit none of the Siagraphs examined for the case or control groups aroused suspicion of dysplastic naevus or melanoma and no significant structural changes were noted during the observation period. However, 2.1% of the melanocytic naevi in the pregnant group increased and 1.3% decreased in size. Corresponding figures in the non-pregnant group were 1.8% and 0%, respectively. Only one naevus in a pregnant woman increased slightly in epidermal pigmentation, and a decrease in pigmentation was noted in 3.7% of the melanocytic naevi in the cases and 1.8% in the controls. None of the differences within or between the groups was statistically significant. We conclude that pregnancy does not influence the appearance of pigmented naevi. A changing naevus during pregnancy should be examined carefully and considered for excision and histopathology.