Long-term survival in malignant melanoma with special reference to age and sex as prognostic factors.

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.

Trends in survival from malignant melanoma: remarkable improvement in 23 years.

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.

Increasing survival trend after cancer diagnosis in Sweden: 1960-1984.

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.

Survival in women receiving hormone replacement therapy. A record-linkage study of a large population-based cohort.

Survival was studied in a population-based cohort of over 23,000 women who were prescribed hormone replacement therapy. Complete follow-up through 1986 revealed a total of 1472 deaths, which was somewhat lower than expected; the relative survival being 101.1% (95% CL, 100.8, 101.3) after 5 years and 102.4% (95% CL, 101.9, 102.8) after 10 years. The relative survival increased with increasing age at entry into the cohort, being 98.2% (95% CL, 96.6, 99.8) in the 40-44 and 105.2% (95% CL, 101.4, 109.1) in the 65-69 year age group after 10 years. Neither the type of compound (potent vs non-potent estrogens), nor the year of entry into the cohort seemed to affect survival, whereas survival advantage generally increased with years of follow-up. Multivariate analysis showed that age at time of first prescription was the only determinant that significantly affected the death risk. This pattern could be explained by confounding due to selection of healthy subjects receiving hormone replacement therapy and/or by the specific choice of estrogen compounds (and progestogens), related to age. It is concluded that hormone replacement therapy is associated with a survival which is similar to or--notably at ages above 50-60 years--slightly higher than that in the general population.

The Swedish Two-County Trial twenty years later. Updated mortality results and new insights from long-term follow-up.

The benefit of invitation to mammographic screening observed in this trial is maintained as a highly significant 32% reduction in breast cancer mortality. Mammographic screening for breast cancer continues to save lives after up to 20 years. Screening derives this benefit by improving the distribution of tumors diagnosed with respect to prognostic categories based on node status, size, and histology of tumors. There is potential for modern screening programs with shorter interscreening intervals to achieve even greater improvements in prognostic category and greater reductions in breast cancer mortality. Mammography can discriminate a subpopulation of high-risk cases, those displaying casting-type calcifications on the mammogram, among very small tumors, with fundamental implications for diagnosis and treatment.

Mammographic screening in women with a family history of breast cancer: some results from the Swedish two-county trial.

BACKGROUND: The objective of this study is to compare the effectiveness of mammographic screening in women with a family history of breast cancer to those without. In the invited arm of a randomised trial of breast cancer screening, data on family history of breast cancer were available on 29.179 women aged 40-74 attending for screening. Among those women, 358 were diagnosed with breast cancer during the trial. METHODS: Those with and without a family history were compared with respect to mammographic parenchymal pattern, interval cancer rates, mean sojourn time and sensitivity of screening. In the 358 cancers, the effect of family history was estimated on survival, incidence of advanced cancers and their relationship to screen detection. RESULTS: A significantly higher proportion of high risk mammographic patterns was observed in association with family history among women aged 40-49. Interval cancer rates were higher in women with a family history, and in older women at least, mean sojourn time was shortened in women with a family history (1.89 years compared to 2.70). Survival was better (although not significantly so) in cancers in women with a family history (relative hazard=0.52) independently of detection mode and was significantly poorer in interval cancers then screen detected cancers (relative hazard=2.72) independently of family history. Similarly, interval cancers tended to be larger, and worse malignancy grade in those with and without a family history of breast cancer. CONCLUSIONS: These results suggest that the policy often adopted of annual screening for woman aged 40-49, with a family history of breast cancer, is a reasonable one, and that it may also be necessary to shorten the inter-screening interval to one year in women aged over 50 but with a positive family history.

Long-term survival in patients operated on for benign peptic ulcer disease.

Survival rate was analysed in a cohort of 6459 patients who had undergone partial gastrectomy for benign ulcer disease and who had survived the first year after operation. The cohort was followed for 27-35 years. There was a slight but significant decrease in relative survival rate to 92 per cent (95 per cent confidence interval 87-97 per cent) 35 years after operation. No decrease in relative survival rate was observed during the first 20 years after operation. There was no difference by gender or surgical procedure, but patients operated on for gastric ulcer, compared with duodenal ulcer, and patients operated on at younger ages had a poorer relative survival rate. The effects of partial gastrectomy on survival, both overall and by diagnosis or age at operation, are probably attributable to confounding factors linked with the peptic ulcer disease rather than to the surgical procedure itself. We conclude that partial gastrectomy seems to have very little impact on survival once the patient has survived the first year after operation.

Unaltered risk of colorectal cancer within 14-17 years of cholecystectomy: updating of a population-based cohort study.

The incidence of colorectal cancer after cholecystectomy was analysed in a historical population-based cohort study comprising 16,439 patients who were completely followed up for 14-17 years after operation. The observed number of colorectal cancers (150) was lower than the expected number of 166.3 (relative risk (RR) = 0.90:95 per cent confidence limits 0.77-1.05) and the overall risk for colon cancer (RR = 0.95) did not differ significantly from that of rectal cancer (RR = 0.82). Separate analyses by sex, age at operation and duration of follow-up revealed relative risks close to or lower than unity. Some deviations indicating a substantially reduced risk might have been due to the play of chance alone. Our results contradict the idea both of a causal and of a non-causal association-through common aetiological factors-between surgically confirmed gallbladder disease and colorectal cancer.

Detection method, tumour size and node metastases in breast cancers diagnosed during a trial of breast cancer screening.

The relationship between tumour size and lymph node metastases was examined in screening-detected and clinically detected breast cancers. The data used were from a randomized trial of breast cancer screening with mammography. 964 cancers were reviewed, in both arms of the trial, in women aged 40-74. Lymph node status was significantly related to detection method (P less than 0.001), metastases being less common in screening-detected cancers. Node status was also significantly related to tumour size (P less than 0.001), metastases being commoner in larger tumours. Similarly, tumour size was significantly associated with detection method (P less than 0.001), smaller tumours being detected by screening. No significant interaction was observed among all three factors, indicating that the relationship between node status and tumour size did not change with detection method. When detection method was replaced with randomly allocated study (invited to screening) and control (not invited to screening) groups, the same results were observed. It is concluded that if screening detects tumours with a different natural history to that of those which surface clinically, this is not reflected in the relationship between tumour size and lymph node metastases.

The risk of gastrointestinal and other primary malignant diseases following gastric cancer.

The risk of developing a second primary cancer was studied among 34,506 gastric cancer patients identified through the Swedish Cancer Registry. A second cancer was reported in 962 patients compared to an expected number of 826 (relative risk = 1.16, 95% confidence limits = 1.09-1.24). The slightly but significantly elevated risk was largely confined to the first year after the gastric cancer diagnosis, and to patients under 70 years old at the time of diagnosis. The risk was significantly increased for cancer in the small intestine, colon, rectum, kidney, breast and prostate. A closer look at the data, however, revealed that a substantial proportion of the second cancers were diagnosed within one month after the gastric cancer diagnosis, or at autopsy. We recalculated the relative risk estimates under the assumption that only 75% of the cancers incidentally detected in connection with diagnosis/treatment of the gastric cancer would have become clinically manifest during the relatively short observation time. and that 20% of the cancers revealed at autopsy in the gastric cancer patients would have been detected if the death and autopsy rates in this group had been equal to those in the general population (matched for age and gender). Under those assumptions the risk of having a second primary cancer among gastric cancer patients was close to what would be expected. The increased risk reported in some previous studies could be the result of closer patient surveillance.

On the age-dependent association between cancer of the breast and of the endometrium. A nationwide cohort study.

The association between breast and endometrial cancer was investigated in a cohort consisting of 60,065 subjects (99% of all women in whom a first breast cancer was diagnosed in Sweden in 1960-63 and 1968-81). Complete follow-up until 1981 revealed a total of 260 endometrial cancers, as against an expected number of 151.1 (relative risk (RR) = 1.72; 95% confidence limits (CL) 1.46; 1.87). RR increased steadily from close to unity in women younger than 50 at breast cancer diagnosis to 2.40 (CL 1.97; 2.93) in those 70 years of age and older. The excess number of endometrial cancers occurred primarily during the first five years of follow-up (RR = 2.07; CL 1.79; 2.38). A common causal agency for breast and endometrial cancer is more likely to lie in environmental than in genetic factors and other observations in the same population do not support that such factors are related to characteristics of the women's reproductive histories.

The risk of hip fractures in patients with primary hyperparathyroidism: a population-based cohort study with a follow-up of 19 years.

OBJECTIVE: To evaluate primary hyperparathyroidism (HPT) as a risk factor for hip fractures. DESIGN: A population-based, record-linked, prospective study with a mean observation time of 17 years (women) and 16.5 years (men). SETTING: A cohort obtained from a register of hospital admissions in the Uppsala Health Care Region, Sweden, 1965-1983. PARTICIPANTS: All patients (1373 women and 551 men) who were admitted to hospital with the diagnosis of HPT during the period. Comparisons were made with the entire background population. MEASUREMENTS: Cohort subjects were followed with regard to a first instance of hip fracture prior to or after the diagnosis of HPT. The observed number of cases was compared with that expected on the basis of person-years of observation and incidence rates in the background population. Analyses were made for cervical and trochanteric fractures, and for patients operated and not operated for HPT. MAIN RESULTS: (i) Women. During 23,341 person-years of observation, 67 cases of first hip fractures occurred, yielding a relative risk (RR) of 0.93 (95% confidence interval [CI] 0.72-1.19). The RR for cervical fractures was 0.77 (CI 0.54-1.06), and for trochanteric fractures 1.33 (CI 0.88-1.93). Operation for HPT did not influence the risk of hip fracture. (ii) Men. The total person-years was 9091. Eleven fractures were observed--compared with the expected 7.90 (RR 1.39; CI 0.69-2.50). Men operated for HPT had an increased risk for cervical hip fractures (RR 2.73; CI 1.18-5.39). Owing to the few fractures in this group (n = 8) the relevance of this is uncertain. CONCLUSIONS: This study indicates that HPT is not a risk factor for hip fractures in women.

Fracture of the distal forearm as a forecaster of subsequent hip fracture: a population-based cohort study with 24 years of follow-up.

OBJECTIVE: To determine the long-term risk of hip fracture following fracture of the distal forearm. DESIGN: Registry-based cohort study comparing patients with a fracture of the distal forearm with a population-based cohort. FRACTURE COHORT: All women and men above 40 years of age with a radiologically verified fracture of the distal forearm during a 5-year period, 1968-1972, in all 1,126 women and 212 men. CONTROL COHORT: An equal number of population-based, age- and sex-matched control persons selected from a population register. MEASUREMENTS: All cohort members were followed up individually through record linkage until the first hip fracture, emigration, death, or the end of 1991. The cohort members contributed a total of 40,832 person-years of observation, and altogether 365 cases of hip fractures were observed. RESULTS: Both women and men with a fracture of the distal forearm ran an increased risk of sustaining a subsequent hip fracture. The overall relative hazard for the women was 1.54 and for men 2.27. The increased risk in the women was independent of age at inclusion, but that in the men was more pronounced in the younger age groups. CONCLUSIONS: Patients with a fracture of the distal forearm run an increased risk of sustaining a subsequent hip fracture. They therefore appear to constitute a group in which appropriate prophylactic measures against osteoporosis and fractures should be considered.

Increased risk of malignant diseases after surgery for primary hyperparathyroidism. A nationwide cohort study.

A cohort of 4,163 persons reported to the nationwide Swedish Cancer Registry by reason of hyperparathyroidism was followed for up to 22 completed years (24,593 person-years of observation). The occurrence of malignant disease manifested after parathyroid surgery was investigated through computerized linkage to the entire Cancer Registry. During the entire period, the hyperparathyroidism patients suffered malignant diseases significantly more often than the background population (relative risk (RR) = 1.6, 95% confidence interval (CI) 1.5-1.8). Even if all cases with malignant diseases detected at the same time as hyperparathyroidism or during the first year after parathyroid surgery were eliminated, a significantly increased risk remained for the following years (RR = 1.4, 95% CI 1.2-1.6). A significantly increased relative risk of developing gastrointestinal cancers, endocrine tumors, kidney carcinomas, and mammary carcinomas was found. During the first postoperative year, an increased surveillance of the cohort is likely to have contributed to the increased risk, but detection bias is considered unlikely to be the only explanation for the higher risk during all subsequent years. The findings indicate that hyperparathyroidism either promotes later development of malignant tumors or that this condition and certain malignant diseases have etiologic factors in common.

Trends in childhood and adolescent cancer survival in Sweden 1960 through 1984.

The temporal changes in childhood and adolescent cancer survival in Sweden 1960-1984 were analyzed. Complete follow-up through 1986 of 6,262 patients younger than 20 years at diagnosis revealed that the overall 5-year survival rates increased from 36.1 to 65.7% in males and from 43.6 to 73.6% in females. The temporal trends differed markedly between age groups and tumour sites and types. Over the study period, 5-years, survival for testicular cancer increased from 46.9 to 87.2%, kidney cancer, predominantly Wilms' tumour from 35.5 to 77.1% (with a higher rate of 89.1% in 1975-1979), Hodgkin's disease from 61.2 to 91.9%, non-Hodgkin's lymphoma from 32.5 to 76.6%, and all leukemias from 8.9 to 58.7%. Only a moderate improvement was noted for tumours of the bone, muscle and connective tissue, and survival rates for tumours of the nervous system remained largely unchanged. Our data reflect the remarkable therapeutic improvements that have occurred for cancer in the young and indicate that these improvements have rapidly become available in Sweden.

Prognosis after breast cancer diagnosis in women exposed to estrogen and estrogen-progestogen replacement therapy.

The association between survival in breast cancer and menopausal hormone treatment prior to diagnosis was analyzed by comparing 261 women who developed the disease in a population-based cohort of estrogen-treated women with 6,617 breast cancer patients without any recorded estrogen treatment drawn from the same population. Complete follow-up was achieved during the 0-9 years of observation. The relative survival rate was significantly higher (p = 0.02), by about 10 percentage points at eight years, in patients who had received estrogen treatment--corresponding to an approximately 40% reduction in excess mortality. The more favorable course could be confirmed only in patients aged 50 years or more at diagnosis (p less than 0.01) and was most pronounced in recent users, that is, in women whose treatment was ongoing (p less than 0.01) or had been discontinued within one year prior to diagnosis. The time from first use to diagnosis and the total duration of estrogen medication were virtually unrelated to survival when the effect of recency was taken into account in multivariate analyses. The authors were unable to examine the effect of stage at diagnosis on the results. Several factors, particularly selection bias and surveillance bias, might have affected the results in favor of the women receiving hormone replacement therapy, but there is a possibility that exogenous female sex hormones affect survival in women with breast cancer.

Colorectal cancer after cholecystectomy: absence of risk increase within 11-14 years.

The importance of cholecystectomy as a risk factor for colorectal cancer was analyzed in an historical cohort study covering 16,773 cases during 11-14 years completed after operation. The observed number of colorectal cancers (130) was lower than the expected 153.5 [relative risk (RR) = 0.85]. For cancer of the colon, the observed number was 87, which was near the 91 expected (RR = 0.95). A significantly increased risk (p less than 0.05; RR = 2.86) was found for cancer of the colon only during the first year after cholecystectomy, and this was judged to be due to cancers present but overlooked at the time of cholecystectomy. The incidence of rectal cancer was significantly decreased (RR = 0.69; p less than 0.05), with 43 observed versus 62.4 expected cases. The distribution of right-sided versus left-sided cancers within the cohort did not differ significantly from that in the general population. Our results do not as yet support previous epidemiologic observations of an increased risk of colorectal cancer after cholecystectomy.

Population-based study of cancer risk and relative survival following sphincterotomy for stones in the common bile duct.

BACKGROUND: Endoscopic sphincterotomy was introduced in 1974 as a procedure for removing stones in the common bile duct. To assess the long-term risk of cancer and relative survival, all patients who underwent this procedure at six different hospitals between 1977 and 1985 were identified. METHODS: A total of 992 patients was identified and they were followed by linkage to the Swedish Death Registry and the Swedish Cancer Registry. RESULTS: At 1 year or more after sphincterotomy there was no increased risk of cancer in the liver, gallbladder, bile duct or pancreas (standardized incidence ratio 0.80, 95 per cent confidence interval 0.3-1.9). Relative survival was lowered slightly in the first year after sphincterotomy, but did not differ from that of the background population thereafter. CONCLUSION: Endoscopic sphincterotomy for stones in the common bile duct does not appear to affect the risk of cancer in the pancreas, liver or bile ducts, nor does it affect long-term survival.

Cholecystectomy and the incidence of breast cancer: a cohort study.

A cohort comprising 11678 women who had undergone cholecystectomy in the period 1964 through 1967 for a benign gallbladder disease was investigated. They represented almost a total ascertainment from a defined geographic area. Follow-up during 11-14 completed years of observation revealed a total of 202 breast cancer cases after the cholecystectomy. This number was close to the expected incidence of 199.1 (relative risk 1.0). Further analysis of the risk in relation to duration of observation and age at operation did not reveal any trend or subgroup with a significantly increased or decreased risk. It was concluded that despite the many epidemiologic observations indicating that in Western Countries dietary habits are particularly important determinants of the high incidence of both gallstone disease and breast cancer, our results contradict the idea that the diseases share common aetiologic factors.

Survival after rectal cancer: differences between hospital catchment areas. A nationwide study in Sweden.

BACKGROUND: The quality of rectal cancer surgery at small units has been debated. No national studies of this issue have been undertaken and most studies have been based on insufficient data to clarify the controversy. It has been claimed that observed differences in outcomes between specialised centres and smaller hospitals are confounded by differences in stage/severity. AIM: To compare survival after rectal cancer between hospital catchment areas. PATIENTS: All patients with rectal cancer notified to the Swedish Cancer Register in 1973-1992 (n = 30 811) were followed up by record linkage to the nationwide Death Register. METHODS: Relative survival-that is, ratio of observed to expected survival-was computed as a measure of excess mortality attributable to rectal cancer. Multivariate analysis was then performed to estimate the independent effects of hospital catchment area categories and age, year of diagnosis, and duration of follow up. RESULTS: One year relative survival among rectal cancer patients residing in catchment areas of large regional hospitals was 76%, compared with 72% for small local hospitals (p<0.001). A difference was already noted after 30 days and remained five years after diagnosis. Relative survival improved considerably overall, but the differences between catchment area categories persisted. These were not reduced by adjustment for age, time after diagnosis, or time period in multivariate models. CONCLUSION: The differences in outcome between catchment area categories could not be explained by differences in age, time period, or duration of follow up after diagnosis. They are unlikely to be explained by differences between catchment area populations with regard to the average stage of the disease at which symptoms lead to diagnosis. The differences may therefore be attributable to different strategies for diagnosing and managing patients with rectal cancer.