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Neuroblastoma is an embryonal tumour of the sympathetic nervous system with marked heterogeneity in terms of histological maturity and clinical course. A previous study revealed that high tumour levels of the csrc protein, particularly its neuronal isoform (pp60csrcN), correlated with favourable outcome. To test whether this feature reflects a higher degree of neuronal maturation in these tumours, an extended series (47 consecutive neuroblastomas and 10 ganglioneuromas) were analysed for levels of csrc protein isoforms, neuron-specific enolase, and synaptophysin. Immunoblotting and radioimmunoassay techniques were employed. The results were compared with conventional histological signs of neuronal maturation. High pp60csrcN levels were specific for prognostically favourable neuroblastomas and correlated with high neuronal marker levels. However, signs of histological maturation correlated poorly with these parameters. It is therefore concluded that low stage tumours are highly differentiated in biochemical terms despite their frequently immature histology. Furthermore, the clinical usefulness of these biochemical parameters as prognostic markers was compared with established parameters in a multivariate analysis. Stage 4 disease, MYCN amplification, and age above 18 months at diagnosis was the most powerful combination of variables found for predicting a poor outcome. As expected, none of the neuronal differentiation markers investigated could add to the prediction of aggressive disease when compared with this model. However, high expression of pp60csrcN appeared to be useful in predicting long-term survival in high stage infant neuroblastoma.

The association between parity and risk of thyroid cancer was examined in a case-control study nested within a cohort of Swedish women born 1925-60. A total of 1,409 cases of thyroid cancer were compared with 7,019 age-matched controls. Odds ratios (OR) and 95 percent confidence intervals (CI) were calculated as estimates of relative risk. A weak association was found between parity and risk of thyroid cancer (OR for ever-parous women cf nulliparous was 1.1, CI = 1.0-1.3). For the subset of papillary cancers, there was a significantly increased risk (OR for ever-parous cf nulliparous = 1.3, CI = 1.0-1.6), and among women diagnosed at the age of 50 or older, there was a positive linear trend with increasing number of livebirths. Women during the first year after a livebirth had an increased risk of thyroid cancer compared with women who delivered 10 or more years before; this association was most prominent among uniparous women (OR = 2.5, CI = 1.1-5.9). An increased risk was also apparent for age over 20 years at livebirth (among uniparous women) and age over 25 years at last livebirth (among multiparous women). A negligible effect of parity on thyroid cancer risk was seen, but each livebirth may have a short-term and age-dependent promoting effect.

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.

A cohort of 559 patients in Sweden who satisfied predetermined criteria for the diagnosis of primary biliary cirrhosis was followed with respect to the incidence of cancer during the period of 1958 to 1988. The mean follow-up time from the time of primary biliary cirrhosis diagnosis was 9.0 +/- 5.4 yr. During the follow-up period, 148 patients died and the primary cause of death was liver insufficiency. An overall excess risk for cancer, standardized incidence ratio 1.6; 95% confidence interval, 1.1 to 2.2, was found in the cohort. In contrast to previous reports, we found no excess risk for breast cancer (standardized incidence ratio, 0.9; 95% confidence interval, 0.3 to 2.1). The number of hepatocellular cancers in the primary biliary cirrhosis cohort did not significantly differ from expected (standardized incidence ratio, 2.91; 95% confidence interval, 0.4 to 10.5).

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.

A longitudinal study of altogether 1462 women aged 38 to 60 years started in Gothenburg, Sweden in 1968-69. Based on information from the population study and from the Swedish Cancer Registry 35 women had a history of malignant disease when initially examined in 1968-69. During a 12-year follow-up period a total of 79 malignant tumours developed in 73 women. A comparison was made between the 1988 Cancer Registry listing and the observations made in the population study. All but one out of 103 cases (99%) were registered in the Cancer Registry and all but one (99%) in the population study. It may be concluded that the accuracy of the population study registration as well as that of the Cancer Registry at that time were very high. This enables us to draw relatively safe conclusions from our own material when testing for risk factors.

Background: Cytologic screening can reduce mortality from cervical cancer by detection and removal of premalignant lesions. Conceivably, mortality is further reduced because more women with invasive disease are diagnosed at an earlier, curable stage. This hypothesis can be assessed in Sweden, where population-based screening programs were introduced successively over about a decade starting in 1964., Methods: Record linkages permitted complete follow-up through 1986 of all 17,377 patients with invasive cervical cancer diagnosed in Sweden from 1960 through 1984. We analyzed relative survival rates that describe the survival of patients after elimination of the effects of causes of death other than cancer of the cervix., Results: Prognosis improved substantially in patients younger than age 50 years at diagnosis; from 1960-1964 to 1980-1984, the 5-year relative survival rate increased from 69.8% to 88.8% at age 20-29 years, from 71.7% to 85.5% at age 30-39 years, and from 68.6% to 77.9% at age 40-49 years. The excess mortality was thus reduced by more than half in patients diagnosed when younger than 40 years. In contrast, only slight or no improvement was noted in those diagnosed at older ages when screening was less extensive. In all time periods, a strong association was found between older age at diagnosis and poorer prognosis., Conclusion: Although alternative explanations for our findings must be seriously considered, the most obvious interpretation is that cytologic screening reduces mortality from cervical cancer by earlier diagnosis of invasive disease.

Statistics from the Swedish National Cancer Registry based on all 110,658 cases of invasive breast cancer during the 31-year period 1958-1988 were analysed. Age-specific incidence rates increased over successive calendar periods. The average annual increase in the age-standardised incidence rate was 1.3%, with the greatest percentage changes among the youngest age groups. During the latter half of the study period, the rates of increase tended to diminish in the youngest age groups and even reversed significantly among women from 75 years of age. In analyses using age-period-cohort models, the best fit of the cancer incidence data was found for the full model which simultaneously considered the effects of age, period and cohort. Cohort effects were found to be more important than period effects, in terms of model fit. These effects emerged as a seemingly consistent, and in a logarithmic scale, fairly linear increase in the relative risk of breast cancer incidence with a 3-fold elevation in women born in the 1950's relative to those born in the 1880's. It is concluded that the rising breast cancer incidence in Sweden is explained chiefly by birth cohort effects, which indicate persistent secular changes in largely unknown risk factors associated with life style. We could not in the present data see any clear evidence for an adverse effect of contraceptive or replacement sex steroids on breast cancer incidence.

Background: Cytologic screening and follow-up can reduce the incidence of cervical cancer by detection and removal of precursor lesions. It is unknown, however, whether differences in histopathologic criteria for these precursor lesions affect the benefit of screening. These criteria may be difficult to study, but they are likely to be reflected in reported incidence of in situ cancer in small areas of Sweden., Purpose: Our purpose was to test the hypothesis that the benefit of screening can be predicted by histopathologic criteria as reflected in the reported incidence of cancer in situ., Methods: Incidence data were from the Swedish National Cancer Registry. Regression models showing the relationship between in situ and invasive cancer were formulated and estimated. Each county (total, 24) was a unit of measurement, and adjustment was made for the incidence of invasive cancer before screening., Results: During population-based screening in Sweden, the incidence of cancer in situ varied about fourfold among the 24 counties, which indicates that the criteria used to diagnose cancer in situ differed markedly. No statistically significant (P < .05) associations were found between the incidence of cancer in situ in 1965, 1970, or 1975 and the reduction in invasive cancer 5, 10, or 15 years later. According to the best-fitting model, detection of 100 extra cases of cancer in situ per 100,000 women per year in 1975 resulted in a reduction of 1.0 (95% confidence interval [CI] = -1.6-3.7) cases of invasive cancer 10 years later. The corresponding best model estimate implied a reduction of 4.6 cases (95% CI = 1.5-7.7) in a model restricted to cancer in situ in patients aged 20-50 years (when organized screening took place), invasive cancer in patients aged 30-60 years, and cancer in situ measured in 1970., Conclusions: The absent, or at most weak, association between detection of cancer in situ and subsequent reduction in invasive cancer indicates that relaxed histopathologic criteria for cancer in situ may result in extensive, unnecessary treatment of lesions that would regress spontaneously., Implication: Further studies are urgently needed to enable identification of neoplasms likely to progress to invasive, fatal disease.

Although a rare tumor form, there is evidence that the incidence of esophageal adenocarcinomas is increasing in Western Europe and the US. The aim of this nationwide population-based study was to describe the secular trends in the incidence rates of adenocarcinoma and squamous-cell carcinoma of the esophagus over a 28-year period from 1960 to 1987. The Swedish Cancer Registry, complete to more than 95%, was used to identify the cases. The percentage verified by histology rose from 89% to 98%. The age-standardized incidence rate of adenocarcinoma increased in males from 0.5 per 10(5) in 1960-63 to 1.1 per 10(5) in 1984-87, corresponding to an average annual increase of 1.5%. In females the incidence remained stable around 0.2 per 10(5). The age-standardized incidence rate of squamous-cell carcinoma in males increased from 2.9 to 4.0 per 10(5), corresponding to an average annual increase of 1.0%. In females the rate decreased from 1.4 to 1.2 per 10(5), corresponding to an annual average decrease of 0.5%. The male/female ratio was 4.6 for adenocarcinoma and 2.7 for squamous-cell carcinoma of the esophagus. Since the incidence rates of squamous-cell carcinoma of the esophagus and of adenocarcinoma seem to be rising, there is a great need for well-planned analytical epidemiological studies of these tumor locations, taking the histological type into consideration.

There is controversy about cancer mortality trends; some analyses show increasing mortality, but others suggest that rates are falling in the youngest age groups. We have investigated trends in cancer incidence in the whole of Sweden for the period 1958 to 1987. 837,085 cancer cases were registered during the period studied. Incidence rate patterns were studied by age-period-cohort modelling. The risk of cancer was higher for people born during the 1950s than for those born in 1873-82; for women the risk was doubled and for men it was trebled. Although the rate of increase slowed, it showed no sign of levelling off in the youngest birth cohorts. The frequency of smoking-related cancers increased greatly in both sexes, but such tumours could explain only part of the rise in total cancer. These trends predict a continuing rise in the incidence rate of cancer, and suggest a worrying pattern of increasing population exposure to carcinogenic influences.

Several American, Japanese and European centres have reported an increase in carcinoma of the gastric cardia, contrary to the general trend in the incidence of gastric cancer. The aim of this nationwide population-based study was to describe trends in the incidence of tumours of the gastric cardia in Sweden over the 16-year period from 1970 to 1985. The Swedish cancer register, which is more than 95 per cent complete, was used to identify cases. There were 1514 men and 481 women with cancer of the gastric cardia. The age-standardized rates increased in men from 1.9 per 10(5) population in 1970-1973 to 3.0 per 10(5) in 1982-1985, corresponding to a mean annual increase of 2.5 per cent (95 per cent confidence interval (c.i.) 1.6-3.4 per cent). In women, the age-standardized rates increased from 0.5 per 10(5) in 1970-1973 to 0.8 per 10(5) in 1982-1985, the mean annual increase being 0.9 per cent (95 per cent c.i. 0.0-1.8 per cent). The highest incidences were found in southern Sweden, contrary to the geographical distribution of gastric cancer in general, which shows a south-to-north gradient. The disparate epidemiological features of cancer of the cardia and gastric cancer at other sites suggest that the aetiologies may also be different. Since little is known about the aetiology of cancer of the cardia, and the incidence seems to be rising rapidly, analytical studies are urgently needed.

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.

Rough estimates of the effect in 2005 of various preventive measures aimed at reducing cancer mortality in the Nordic countries were made using the American software CAN*TROL. The effect was measured as the percentage reduction in cancer mortality in 2005. The calculations were performed for changes in the smoking, dietary and sunbathing habits of the population (primary prevention), earlier diagnosis (secondary prevention) and improvements in survival resulting from better treatment (tertiary prevention). The calculations incorporate many assumptions, some of them more firmly based than others, such as uniformity of incidence trend in all the Nordic countries and also concerning the causality of various relations. For lack of evaluated Nordic data, we have used American figures concerning stage distributions and stage-specific relative survival rates. These assumptions should be borne in mind when drawing conclusions from the results obtained. The results show that there is a potential of up to several tens of percent for reducing total cancer mortality by the year 2005.

Approximate estimates have been made of the effect by the year 2005 of various preventive measures to reduce cancer mortality in Scandinavia. Figures have been calculated for changes in smoking, diet and exposure to sunlight (primary prevention), for earlier diagnosis (secondary prevention), and improved survival as a result of improved treatment (tertiary prevention). The calculations have been performed with the American program CAN TROL, the effect being expressed as the percentage reduction in cancer mortality by the year 2005. The results give promise of a substantial overall reduction in cancer mortality in Scandinavia.

Trends in the incidence of stomach cancer among 52,604 patients notified to the National Swedish Cancer Registry in 1960 through 1984 were analysed. Age-standardized incidence rates declined throughout the period, from 47.1 to 24.6 per 10(5) in males and from 23.8 to 12.7 per 10(5) in females. Among males the decline in incidence was more pronounced in younger age strata, 35-54 years, while in females it reached a maximum at ages 70-74 years. In a multivariate analysis the age-cohort model adequately represented the data and there was no reason to separate the effects of the full age-period-cohort model. Compared with the cohort born in 1876-1884, the relative risk of developing stomach cancer was 0.46 (95% CI:0.44-0.48) in males and 0.39 (95% CI:0.37-0.42) in females born in 1906-1914. This supports the view that the declining incidence is due to a change in the exposure of the population to aetiological factors of stomach cancer and not to refinement of the diagnosis and classification of abdominal tumours. The results also imply that exposure to aetiological factors early in life together with a long induction period is of importance in the development of stomach cancer.

Survival, i.e. the time from report to cancer registry to death was studied for 591,456 cases of cancer diagnosed in vivo from 1960 to 1984. Ten years survival increased from 35 to 40%. Survival rates for women were higher than for men. Since 10 years survival almost suggests cure, lead time bias is assumed not to be a major factor. Nor are relaxed histological criteria, detecting non-fatal tumors, intensified microscopic examination, changes in the relative frequency of cancer types, or increasing numbers of elderly patients assumed to be major artefacts. In contrast, improved socio-economic and health status are. Early detection also improves survival in some cancer types.

Trends in incidence of and mortality from invasive endometrial cancer in Sweden in 1960-84 were analyzed. The study was based on virtually all 20,371 patients given this diagnosis and 4,887 patients who died of the disease in that period. Only minor changes occurred in age-standardized incidence in pre-menopausal women, in whom the rates declined consistently during the last 15 years, especially in the youngest age groups. Among post-menopausal women, an early increase was followed by stable rates in women over 60 and decreasing rates at ages 50-59 years. In contrast, mortality rates decreased consistently over the study period. Multivariate regression analyses indicated that birth cohort was a more important determinant of incidence and mortality than was time period. The relative risk of developing endometrial cancer increased by about 20 percent in women born around 1900 as compared with 1880, and by an additional 40 percent from the 1910 cohort to the maximum risk attained in those born around 1930. In successively younger birth cohorts, the risk markedly and continuously declined. These strong birth-cohort effects after 1910 may be reasonably explained by the change from the risk-increasing estrogen-only replacement therapy introduced in the 1960s to the less harmful use, starting about 10 years later, of combined estrogen-progestogen regimens; and further, by the protective exposure of a large proportion of pre-menopausal women to oral contraceptives. Mortality, however, decreased steadily in successive cohorts from those born in 1890, indicating that the increase in incidence was referable mainly to non-lethal cancers.

We analyzed the survival trend after cancer was diagnosed by complete follow-up through 1986 of 591,456 (99.4%) of all those patients in whom a first malignant disease was diagnosed in Sweden from 1960 to 1984. From 1960-1964 to 1980-1984, the 5-year relative survival increased from 34.2% to 47.1% in males and from 48.7% to 56.9% in females. The mean loss of expected life among cancer patients decreased from 9.6 to 7.0 years. During the first 5 years after diagnosis, the cancer-specific hazard rate decreased by 34% in males and 30% in females. Thus several analytical approaches revealed a substantial increase in cancer patient survival since 1960.