Monika Dufmats

Invasive cutaneous malignant melanoma in Sweden, 1990-1999 - A prospective, population-based study of survival and prognostic factors

The objective of the current study was to compile prospective, population‐based data on cutaneous invasive melanomas in Sweden during the period from 1990 to 1999, to describe and analyze survival data and prognostic factors, and to make comparisons with previously published Swedish and international data.

Long-term survival in a Swedish population-based cohort of men with prostate cancer

OBJECTIVES To study the long-term survival of patients with prostate cancer, determine the risk factors for prostate cancer death, and investigate the outcome of initially untreated localized prostate cancer and incidentally detected tumors. METHODS The survival of 813 patients in a population-based cohort of patients with prostate cancer in Linköping, Sweden, diagnosed from 1974 to 1986, was analyzed. RESULTS At 10, 15, and 20 years after diagnosis, the prostate cancer-specific survival rate of men with localized, initially untreated, prostate cancer was 85.0% (95% confidence interval [CI], 79.0% to 91.0%), 80.0% (95% CI, 72.5% to 87.5%), and 62.6% (95% CI, 43.0% to 82.2%). Age 70 years or older, advanced stage, and poor differentiation were risk factors associated with an increased risk of prostate cancer death. At 10 years, the prostate cancer-specific survival rate among men with localized tumors treated by expectancy was 90% (95% CI, 84% to 97%) for grade 1 tumors, 74% (95% CI, 60% to 89%) for grade 2 tumors, and 59% (95% CI, 29% to 90%) for grade 3 tumors. For patients with incidentally detected tumors, the grade of malignancy was a more important risk factor than tumor volume. CONCLUSIONS Patients with localized tumors have a favorable prognosis, even without initial treatment. However, when deciding on therapy, the grade of malignancy should be taken into account, as it has a great influence on survival. We did not see a tendency toward increased mortality when the patients were followed up for longer than 10 years after diagnosis.

Validity of a Population-Based Cancer Register in Sweden An Assessment of Data Reproducibility in the South-East Region Prostate Cancer Register

Background: With a population-based setting, high coverage and accurately recorded data, the validity of a register is guaranteed. The South-East Region Prostate Cancer relies on the National Cancer Register as a basic source of data, thereby ensuring a high coverage of the corresponding geographic area. To assess the reproducibility of the data recorded a random sample of the cases were reviewed a second time and compared to the original recording. Material and methods: The South-East Region Prostate Cancer Register was started in 1987. In addition to the basic data acquired from the Swedish National Register, it also includes tumour stage, grade, treatment and, since 1992, PSA. In the first stage of quality assessment 10 cases for each of the years 1987-1996 from Linköping University Hospital were randomly selected for two independent recodings according to the same protocol as the original registration. In the second step 10 cases each for the same years from the remaining 8 hospitals in the region were selected for a single recoding. Results: No systematic deviations were seen between the two independent recodings from Linköping, a single recoding was therefore considered sufficient for assessing the reproducibility of the data from the remaining hospitals in the region. The Kappa values for agreement between the original registration and the single recoding ranged from 0.589 to 0.869. Conclusion: The population-based setting and high coverage guarantees the external validity of the register. The internal validity is ensured by the high reproducibility shown in the present study.

Frequent allelic losses at 11q24.1–q25 in young women with breast cancer: association with poor survival

SummaryPrevious studies have demonstrated that the pathological features of breast cancer are more aggressive in younger women than in their older counterparts, and that young age may be an independent marker for adverse prognosis. These findings have raised the question whether these differences are also present at the molecular level. In order to characterize the genetic alterations associated with early-onset breast cancer, 102 cases selected for age under 37 at diagnosis were examined for loss of heterozygosity (LOH) at nine different loci on chromosomes 11, 13 and 17. Ninety cases (88%), exhibited LOH for at least one marker. The D17S855 marker, intragenic in the BRCA1 gene, showed a high proportion of LOH (63%), whereas the intragenic marker for the TP53 gene, HP53, exhibited LOH in 43% of the cases. On chromosome 11, frequencies of LOH peaked at the D11S969 and D11S387 markers, which expressed LOH in 53% and 48% of the informative cases, whereas D11S1818, which is proximate to the ATM gene, exhibited an LOH frequency of 24%. A statistically significant correlation was found between LOH at the D11S387 marker and poor survival (P = 0.028). No such correlation was found for the adjacent D11S969 marker, located approximately 500 kb centromeric to D11S387. We conclude that one or more as yet unidentified genes, situated in chromosome bands 11q24.1–q25, could be involved in the initiation and/or progression of breast cancer in younger women.

Prostate carcinoma trends in three counties in Sweden 1987–1996

To detect changes in the incidence rate and management of prostate carcinoma, all cases of the disease diagnosed in the southeast region of Sweden between 1987–1996 were recorded.

Survival after treatment for breast cancer in a geographically defined population

South East Sweden with 976 000 inhabitants is served by nine hospitals with specialized breast surgeons. Population‐based mammographic screening was introduced in 1986 for women aged 40–74 years. Patients with primary breast cancer were treated according to a joint management programme.

K-ras mutations in colorectal adenocarcinomas and neighbouring transitional mucosa

The K-ras gene in codons 12 and 13 was investigated using allele-specific polymerase chain reaction in matched normal mucosa (n = 106), transitional mucosa (n = 69) and tumours (n = 149) from 149 patients with colorectal adenocarcinomas. K-ras mutations in codon 12 were detected in 41/149 (28%) of tumours and 4/69 (6%) of transitional mucosa samples, but not in the normal mucosa. Further, mutation rates were increased in younger patients (P = 0.001) and in mucinous carcinomas (50%) compared with well differentiated (17%), moderately differentiated (26%) or poorly differentiated (24%) tumours. Our findings indicate that mucinous carcinoma may represent a distinct genetic entity.

Atopic manifestations are more common in Patients with Crohn disease than in the general Population

Background: The role of TNF‐α in Crohn disease is now well established and anti‐TNF‐α is frequently used as a second‐ or third‐line treatment. Tumor necrosis factor‐α (TNF‐α) is traditionally associated with macrophages but has recently also been found in mast cells of the ileal wall in patients with Crohn disease. As it is well known that mast cells and TNF‐α play important roles in atopic manifestations like asthma, allergic rhinitis, and eczema the aim of this study was to investigate whether these are seen more commonly in Crohn patients than in the general population. Methods: Patients with Crohn disease (n = 308), aged 18–50 years, living in the Linköping region in southeast Sweden, were asked to answer a questionnaire regarding the presence of any kind of atopic manifestations. The questionnaire was also sent to 930 controls collected from the Southeastern Region Population Registry. The controls were matched according to age, sex, and place of residence. Results: The response rate among the Crohn patients was 91% (280/308) and among controls 84% (779/930). Eczema was a significantly more frequent manifestation, being almost twice as common in Crohn patients (27%) as in the general population (16%). Adjustment by logistic regression for place of residence, gender, age and coexistence of any other atopic manifestation did not change the odds ratios significantly. Conclusion: Atopic manifestations as a group, and eczema as a single manifestation, are significantly more frequent in Crohn patients than in the general population.

Improved survival for women with stage I breast cancer in south-east Sweden : A comparison between two time periods before and after increased use of adjuvant systemic therapy

Purpose. Continuous minor steps of improvement in the management of breast cancer have resulted in decreased mortality rates during the last decades. The aim of this study was to compare the clinical outcome of patients with stage I breast cancer diagnosed during two time periods that differed with respect to adjuvant systemic therapy. Material and methods. The studied population consisted of all women < 60 years of age, who were diagnosed breast cancer stage I between 1986 and 1999 in south-east Sweden, a total of 1 407 cases. The cohort was divided into two groups based on the management programmes of 1986 and 1992, hereafter referred to as Period 1 and Period 2. Before 1992 the only adjuvant systemic therapy recommended was tamoxifen for hormone receptor positive patients aged 50 years or older. During Period 2 the use of adjuvant treatment was extended to younger patients at high risk, identified by a high tumour S-phase fraction, with either hormonal or cytotoxic treatment. Results. The estimated distant recurrence-free survival rate was significantly higher during Period 2 than during Period 1 (p = 0.008). Subgroup analysis showed that the most evident reduction of distant recurrence risk was among hormone receptor-negative patients (HR = 0.58, 95% CI 0.31–1.09, p = 0.09) and among patients with a high tumour S-phase fraction (HR = 0.53, 0.30–0.93, p = 0.028). The risk reduction between the periods was still statistically significant in multivariate analysis when adjusting for different tumour characteristics and treatment modalities, indicating an influence of other factors not controlled for. One such factor may be the duration of tamoxifen treatment, which likely was more frequently five years during Period 2 than during Period 1. Conclusions. We conclude that the causes of the increase in distant recurrence free survival for women with breast cancer stage I are complex. The results support though that high-risk subgroups of stage I breast cancer patients did benefit from increased use of systemic therapy as a consequence of an updated management programme.