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Background: Although sun exposure is an established cause of cutaneous malignant melanoma, possible interactions with host factors remain incompletely understood. Here we report the first results from a large prospective cohort study of pigmentation factors and sun exposure in relation to melanoma risk., Methods: The Women's Lifestyle and Health Cohort Study included 106 379 women from Norway and Sweden who were aged 30-50 years in 1991 or 1992 when they completed an extensive questionnaire on personal characteristics and exposures. Linkages to national registries ensured complete follow-up through December 31, 1999. Poisson regression models were used to estimate relative risks (RRs). All statistical tests were two-sided., Results: During an average follow-up of 8.1 years, 187 cases of melanoma were diagnosed. Risk of melanoma was statistically significantly associated with increasing body surface area (RR for > or =1.79 m2 versus < or =1.61 m2 = 1.60, 95% confidence interval [CI] = 1.03 to 2.48; P(trend) =.02), number of large asymmetric nevi on the legs (RR for > or =7 nevi versus 0 nevi = 5.29, 95% CI = 2.33 to 12.01; P(trend)<.001), hair color (RR for red versus dark brown or black = 4.05, 95% CI = 2.11 to 7.76; P(trend)<.001), sunburns per year at ages 10-19, 20-29, and 30-39 years (P(trend)<.001, P(trend) =.03, and P(trend) =.05, respectively), and use of a device that emits artificial light (solarium) one or more times per month (P =.04)., Conclusions: Our results confirm previous findings that hair color, number of nevi on the legs, and history of sunburn are risk factors for melanoma and suggest that use of a solarium is also associated with melanoma risk. Adolescence and early adulthood appear to be among the most sensitive age periods for the effects of sunburn and solarium use on melanoma risk. However, it may be too early to see the full effect of adult exposures in this cohort.

The current status of lymphatic mapping and sentinel node biopsy in the treatment of patients with malignant melanoma and breast cancer is described. The possible use of a similar method in patients with colorectal and gastric cancer is outlined. Peroperative lymphatic mapping and identification of sentinel node(s) in patients with gastrointestinal cancer may lead to modified (tailored) resections and extended lymph node dissections only in those patients in whom the sentinel node(s) contains tumour cells. The method offers the possibility of improving staging by identification of patients with early disseminated disease who should be considered for adjuvant treatment or be included in trials of adjuvant treatment to speed up the breakthrough of more effective adjuvant regimens. Large studies are needed to find out if the sentinel node concept is as valid in gastrointestinal cancer as studies so far have shown that it is for malignant melanoma and breast cancer.

We calculated the short-term and long-term risks of developing cancer among 3,766 patients with a diagnosis of cutaneous melanoma in situ in Sweden from 1958 to 1992. In total, 393 patients developed a primary cancer at any site compared with an expected number of 177 [standardized incidence ratio (SIR) = 2.2, 95% confidence interval (CI) = 2.0-2.4]. Patients below 60 years of age at diagnosis had the highest SIR (2.7, 95% CI = 2.3-3.2). The overall risks were similar between men and women. The highest risk was seen during the first year of follow-up, though the risk remained elevated also after 15 or more years of follow-up. For specific sites, the highest SIR was found for developing invasive cutaneous malignant melanoma (SIR = 22.2). The risk of subsequent primary non-melanoma skin cancer was elevated 8-fold in men and almost 7-fold in women. An elevated risk was also found for female breast cancer (SIR = 1.4). Especially among women, other sites with increased cancer risk (though not significant) were non-Hodgkin's lymphoma (SIR = 1.9), multiple myeloma (3.2) and cancers of the colon (1.6) and pancreas (1.6). In conclusion, patients with melanoma in situ run a generally increased risk of developing primary cancers, especially cutaneous malignant melanoma and non-melanoma skin cancer. The increased long-term risk of cancer after diagnosis of melanoma in situ may be due to continuing carcinogenic exposure or to intrinsic tumor susceptibility., (Copyright 1999 Wiley-Liss, Inc.)

We analyzed incidence trends of cutaneous melanoma in situ in Sweden in 1968-1992. Among men, age-standardized rates increased from 0.1/100,000 in 1968 to 2.9/100,000 in 1992, which corresponds to an average annual increase of 15.0%. Among women, rates increased from 0.3 to 3.7, and the annual increase was 12.8%. Age-specific rates increased since 1978, predominantly in men aged 45 years and older, whereas in women rates increased in all ages. Multivariate analysis showed that incidence rates could be explained by both cohort effects and period effects in addition to age. However, cohort effects seemed more important among men than among women, in whom period effects dominated. Thus, factors associated with the development of melanoma in situ may differ between the sexes. Melanoma in situ is an immediate precursor of invasive melanoma, and the increased detection and surgical excision of these tumors will prevent the occurrence of invasive melanoma.

We determined risk factors for late deaths from cutaneous malignant melanoma (CMM) based on clinical characteristics at diagnosis, initial surgical treatment, histopathologic features of the primary tumor and type of eventual recurrences during follow-up. We examined deaths from CMM 8 or more completed years after the initial diagnosis in a case-control study nested in a nationwide cohort comprising all 8,838 patients with CMM diagnosed in Sweden during 1960-1978 with complete follow-up through 1986. There were 285 case patients and 285 control patients, individually matched by sex, age and follow-up time. Conditional logistic regression was used to obtain odds ratios (OR) as estimates of the relative risk. The risk of late mortality increased stepwise, almost 19-fold, with increasing tumor thickness from < or = 0.75 to > or = 7.00 mm. Besides the thickest tumors (> or = 7.00 mm), those of intermediate thickness (1.50-2.49 mm) had the highest risk (OR 8.5). After adjustment for tumor thickness, non-radical primary surgical treatment increased the risk of late mortality almost 3-fold while prophylactic lymph node dissection entailed a significantly reduced risk of late mortality (OR 0.5); the histopathologic features increasing level of invasion and vertical growth phase also remained significantly associated with a poor outcome. In a multivariate model, non-radical primary surgical treatment, prophylactic lymph node dissection, vertical growth phase, level of invasion and lymphocyte reaction were independent predictors of late mortality.

Pigmentary changes during pregnancy and sex-specific differences in incidence patterns of cutaneous malignant melanoma (CMM) suggest that sex hormones may be involved in the development of CMM. We explored possible associations between childbearing and the risk of CMM in a case-control study "nested' in a nation-wide cohort. A total of 4,779 incident cases of CMM in women aged 24-65 were compared with 23,888 individually age-matched controls. Delayed childbearing was associated with an increased risk of CMM, corresponding to approximately 16% per 5 years. Parous women had a significantly lower risk of CMM compared with nulliparous women; in univariate analysis there was an 8% reduction in risk for each additional birth (odds ratio = 0.92; 95% confidence interval = 0.89-0.95). In multivariate analyses the risk of CMM was best explained by a model including both age at first birth and parity. Age at first birth was the most important variable. Time since most recent birth was unrelated to risk of CMM. These findings indicate that early childbearing and multiparity reduce the risk of CMM. Conceivable explanations are hormonal changes induced by childbearing, enhanced immunologic activity via exposure to fetal antigens during pregnancy, or long-lasting effects of pregnancy-associated hyperpigmentation. Our results need confirmation in studies with proper adjustment for confounding; less sun exposure in young mothers and high parity women may represent an alternative explanation but is unlikely to explain entirely the twofold difference in risk found between extreme categories of age at first birth and parity.

To quantify the risk of second primary cancers among patients with cutaneous malignant melanoma, we studied 20,354 patients in the Swedish Cancer Register during 1958-88. A second primary cancer was reported in 1605 patients, compared with an expected number of 1109.5 [standardised incidence ratio (SIR) = 1.45, 95% confidence interval (CI) = 1.38-1.52]. The highest risk was found among patients younger than 60 years. The greatest risk was seen during the first year after diagnosis (SIR = 1.91, CI = 1.69-2.14), but even after long-term follow-up--15 years or more--the risk was still significantly elevated (SIR = 1.56, CI = 1.35-1.79). The strongest association was found for a second primary malignant melanoma (men, SIR = 10.0, CI = 8.26-12.00; women, SIR = 8.66, CI = 7.22-10.30) and non-melanoma skin cancer (men, SIR = 3.58, CI = 2.85-4.44; women, SIR = 2.41, CI = 1.71-3.29). The risk of second cancers associated with tissues of neuroectodermal origin was increased, especially tumours of the nervous system (men, SIR = 1.73, CI = 1.10-2.60; women, SIR = 2.03, CI = 1.45-2.78). The SIR of second cancers involving the immune system was also increased. An excess risk of endometrial cancer was seen (SIR = 1.41, CI = 1.03-1.88), but no significant associations existed for cancers of the breast, ovary, testis or other endocrine glands. Among tumours of the digestive tract, only colon cancer in men had a significantly increased SIR (1.33, CI = 1.00-1.74).

In Sweden, improvement in survival rates of patients with cutaneous malignant melanoma has counteracted the increase in incidence to produce a moderate rise in mortality. Our aim was to determine the possible impact of drift in diagnostic criteria, earlier diagnosis and changing biological features of the tumours upon trends in survival. We studied a stratified sample of 528 patients diagnosed between 1960 and 1984 in a strictly defined geographical region. No evidence of drift in diagnostic criteria was found. The proportion of patients with invasion level Clark II increased from 3.2% in 1960-64 to 22.5% in 1980-84, the proportion of thin melanomas (< or = 0.75 mm) increased from 9.4% to 31.5% and the tumour thickness decreased significantly between each 5 year period of diagnosis. These changes are most likely the results of earlier diagnosis. However, changes in tumour characteristics have occurred, since the proportion of superficially spreading malignant melanoma increased from 35% in 1960-64 to 51% in 1980-84 and the proportion of acral lentiginous melanoma decreased from 11% to 2%. The proportion of nodular melanomas remained fairly constant. The proportion of tumours with lymphocytic reaction did not change, whereas those with histological regression increased slightly. Proportional hazards analyses showed a significantly lower survival in patients diagnosed in 1960-64 but no apparent trend after 1965. This finding remained after adjustment for all studied clinical and histopathological factors which point towards changes in unmeasured biological features of the disease.

Background: Previous malignant melanoma studies regarding prognostic factors have often selected their patients from hospitals. Unfortunately, most of these studies have had small numbers of patients, consisted of short-term data sets, omitted important factors, did not optimize histopathologic classification, had too short or inadequate follow-up, and did not test their predictive models., Purpose: Our study goals were to identify independent clinical and histopathologic determinants of survival in malignant melanoma, to analyze changes in prognostic value over follow-up time, and, finally to construct a prognostic index., Methods: A random sample from the Swedish Cancer Registry of the records of 498 (246 men and 252 women) patients defined by gender, five 5-year time periods of diagnosis from 1960 through 1984, and five anatomic sites formed the cohort on whom data were analyzed by univariate analyses. Multivariate analyses were based on data on 476 patients with complete information about all variables. All patients in the cohort had complete follow-up through December 31, 1989. Clinical information was abstracted and recorded as: date of diagnosis, stage at diagnosis, sex, age, anatomic site of primary tumor, date of death, and cause of death. Histopathologic slides were re-examined and classified with regard to histogenetic type, level of invasion, tumor thickness, ulceration, vascular invasion, regression, lymphocytic reaction, pre-existing nevus, and cell type., Results: All variables, except pre-existing nevus and cell type, were significant predictors of survival. In the multivariate analyses including all variables, women still had a significant, 33% lower relative hazard than men. The prognosis was poor in the youngest age group. Patients with external ear, scalp-neck, and trunk-located melanoma had increasing relative hazard when all variables were included. Regional metastases and tumor thickness remained independent prognostic factors. No significant association between histogenetic type or level of invasion persisted. Patients whose tumors showed ulceration or vascular invasion had lower relative hazard when all variables were included. Level of invasion, tumor thickness, ulceration, and vascular invasion were significantly associated with the prognosis during both short- and long-term follow-up. The patients were subgrouped according to percentage fractions of their score on the prognostic index. Survival curves for these groups of patients were well separated, thus identifying patients with a low or high risk of death from malignant melanoma., Conclusion: The present population-based study identifies independent clinical and histopathologic predictors of survival in cutaneous malignant melanoma and emphasizes the role of histopathologic characteristics such as tumor thickness, ulceration, and vascular invasion besides anatomic site.

We compared measurements of temporal trends in cancer survival either based on observed survival or relative survival. Survival rates for cutaneous malignant melanoma diagnosed in Sweden 1960-1982 were used as an example. In a proportional hazards model based on observed survival, the hazard ratio for patients diagnosed during the period 1975-1979 was 0.56 (95% confidence limits 0.49-0.64) in men and 0.45 (0.38-0.53) in women when the period 1960-1964 was the reference. When relative survival was the outcome measure, during the same period, the hazard ratio decreased to 0.47 (0.39-0.56) in men and 0.36 (0.29-0.44) in women. Thus, the effect of period of diagnosis was larger when the analysis was based on relative survival rates. The reasons for the differences between these two alternative measurements are explained in the article and advantages/disadvantages of the two approaches are discussed.

To monitor mortality rates from malignant melanoma we analysed all patients in Sweden (6,324) who died of malignant melanoma in 1953 through 1987. Age-standardised rates per 10(5) increased from 1.1 to 4.0 in men and from 1.0 to 2.6 in women. The average annual increase levelled off in men from 4.6% during 1953-1967 to 2.0% in 1978-1987; and in women from 3.7% to 0%. Multivariate analyses showed that the change in rates for men was mainly due to a birth-cohort effect, whereas in women the rates changed similarly in all age-groups in accordance with a time-period effect. The risk of dying of malignant melanoma increased in men for birth cohorts up to 1932, whereas in women the rise continued for cohorts born as late as 1947. The best-fitted multivariate models were extrapolated to the year 2007, among men a slight increase in mortality rates seemed likely, whereas among women the rates will probably remain unchanged.

The incidence of cutaneous malignant melanoma has increased more than the incidence of any other malignant tumour disease in Sweden the last three decades. Parallel to the almost 6% annual increase in incidence there has been a 3% annual increase in mortality. The knowledge of significant risk factors for melanoma (intermittent sun exposure and phenotypic traits related to skin pigmentation and propensity for dysplastic nevi) as well as the relationship between thin tumours and a good prognosis has been used to develop strategies for primary and secondary prevention. In this paper the Swedish programs for education of physicians, nurses and the general population are presented. A nationwide program for the identification and follow-up of individuals with dysplastic nevus syndrome has been initiated. The effects of the programs are followed by population-based melanoma registries.

This study was based on 15,376 patients in Sweden with cutaneous malignant melanoma diagnosed during the 25-year period 1960-1984. Trunk melanoma increased substantially during that period among men, with age-standardized rates rising from 1.1 to 7.0 per 10(5). Among women, the greatest increases occurred in melanoma of the upper extremity (rising from 0.4 to 2.3), lower extremity (rising from 1.6 to 4.4), and trunk (rising form 0.6 to 3.1), but the rates for the latter two sites seemed to level off after 1978. Multivariate analyses showed that models based on a common parameter ("drift"), including linear birth cohort and/or time periods effects, were significantly superior to simple age models for explaining incidence trends for each separate site. Further, in men with melanoma of the trunk and upper and lower extremities, birth cohort effects had significant effects compared with drift. In contrast, in women, time period effects were a significant improvement on drift for melanoma of the trunk and lower extremity. The relative risk of malignant melanoma among men leveled off in later-born cohorts for all separate sites. A similar trend was found in women, except for melanomas of the trunk, in which the increase in relative risk persisted. The results indicate sex-specific differences in temporal trends of exposure to factors causing malignant melanoma.

Trends in incidence of and mortality and survival from malignant melanoma in Sweden for 1960 through 1982 were analyzed. Incidence rates increased annually by 5.4% for females and by 5.8% for males, whereas mortality rates increased annually by 2.7% for females and 3.3% for males. For females, the 5-year relative survival (RS) rates increased by approximately 15 percentage points before 1970. In contrast, males before 1970 had a successive improvement in RS rates of 4.6-8.2 percentage points for each 5-year period of diagnosis. Multivariate analyses revealed that during the study period the malignant melanoma-specific hazard decreased by 71% [95% confidence interval (CI) = 59%-79%] for females and by 64% (95% CI = 54%-73%) for males during the first 5 years of follow-up.

The relationship between site and survival in cutaneous malignant melanoma was investigated by a follow-up of 12,353 Swedish patients diagnosed in 1960-1982. In males, the poorest prognosis was found for tumors located on the scalp-neck region (5-year relative survival rate, RS51%), followed by the lower extremity (RS66%) and trunk (RS68%). Among females, the poorest prognosis was noted for tumors located on the external ear (5-year RS 71%), trunk (RS 78%) and scalp-neck (RS 78%). The prognosis varied considerably between the sites of the head-neck region--for eyelid and facial lesions the prognosis was good, but for external ear and scalp-neck tumors it was poor. Multivariate analysis taking into account age and year of diagnosis showed the highest relative hazards (RH) for female lesions of the trunk (1.40) and male scalp-neck tumors (1.65), with the upper extremity used as reference (RH = 1.00). Except for lesions of the trunk, no significant differences in RH were found between the various sites after 4 years of observation.

A total of 12,353 (97.5%) of all patients with a first malignant melanoma newly diagnosed in Sweden during the period 1960-82 were subjected to a complete computerized follow-up with respect to survival through December 31, 1982. Calculation of relative survival rates (RSs) revealed a consistently more favorable course in women than in men, the 5-year RSs being 80.8 and 68.0% and the 10-year RSs being 75.0 and 61.8%, respectively. Prolonged follow-up and analyses of annual excess mortality showed, in addition, that men surviving about 10 years constituted an apparently cured fraction, whereas among women there was an excess mortality throughout the observation period. The prognosis was increasingly more favorable at younger ages in males, whereas no regular age trend emerged in the female group of patients. A multivariate analysis indicated that the findings were not confounded by temporal trends in RSs or by differences in tumor location between the groups compared and also that the relative hazard was significantly higher for men than for women only during the first 8 years after diagnosis.

Abstract: Aims: Lymphatic mapping and sentinel node biopsy entails better staging in malignant melanoma and breast cancer and we used this technique in patients with colon cancer to possibly improve detection of lymphatic spread. Methods: Thirty patients with invasive adenocarcinomas were investigated. The tumour status in identified sentinel node(s) was compared with the status in all other harvested regional nodes for each patient. Patients were followed at regular visits for more than 30 months. Results: Sentinel nodes were identified in all cases, either per-operatively (28 cases) or at dissection of the formalin-fixed specimen (2 cases). The sentinel nodes were diagnostic for the entire lymphatic field in 28 patients and the false negative rate was 2/12. In four cases, the sentinel nodes were the only metastatic nodes. After at minimum 30 months, three patients had died of colon cancer metastases. Conclusion: This method improved the identification of patients with lymph-node metastases, especially those with only few metastatic nodes. Patients dying from metastatic disease had lymph-node metastases at diagnosis. [Copyright &y& Elsevier]

Background: Previous malignant melanoma studies regarding prognostic factors have often selected their patients from hospitals. Unfortunately, most of these studies have had small numbers of patients, consisted of short-term data sets, omitted important factors, did not optimize histopathologic classification, had too short or inadequate follow-up, and did not test their predictive models.Purpose: Our study goals were to identify independent clinical and histopathologic determinants of survival in malignant melanoma, to analyze changes in prognostic value over follow-up time, and, finally to construct a prognostic index.Methods: A random sample from the Swedish Cancer Registry of the records of 498 (246 men and 252 women) patients defined by gender, five 5-year time periods of diagnosis from 1960 through 1984, and five anatomic sites formed the cohort on whom data were analyzed by univariate analyses. Multivariate analyses were based on data on 476 patients with complete information about all variables. All patients in the cohort had complete follow-up through December 31, 1989. Clinical information was abstracted and recorded as: date of diagnosis, stage at diagnosis, sex, age, anatomic site of primary tumor, date of death, and cause of death. Histopathologic slides were re-examined and classified with regard to histogenetic type, level of invasion, tumor thickness, ulceration, vascular invasion, regression, lymphocytic reaction, pre-existing nevus, and cell type.Results: All variables, except pre-existing nevus and cell type, were significant predictors of survival. In the multivariate analyses including all variables, women still had a significant, 33% lower relative hazard than men. The prognosis was poor in the youngest age group. Patients with external ear, scalp-neck, and trunk-located melanoma had increasing relative hazard when all variables were included. Regional metastases and tumor thickness remained independent prognostic factors. No significant association between histogenetic type or level of invasion persisted. Patients whose tumors showed ulceration or vascular invasion had lower relative hazard when all variables were included. Level of invasion, tumor thickness, ulceration, and vascular invasion were significantly associated with the prognosis during both short- and long-term follow-up. The patients were subgrouped according to percentage fractions of their score on the prognostic index. Survival curves for these groups of patients were well separated, thus identifying patients with a low or high risk of death from malignant melanoma.Conclusion: The present population-based study identifies independent clinical and histopathologic predictors of survival in cutaneous malignant melanoma and emphasizes the role of histopathologic characteristics such as tumor thickness, ulceration, and vascular invasion besides anatomic site. [ABSTRACT FROM AUTHOR]