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  • 1.
    Gentile, Massimiliano
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Olsen, K.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Molecular and Clinical Medicine, Forensic Medicine. Linköping University, Faculty of Health Sciences.
    Dufmats, Monika
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Wingren, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Frequent allelic losses at 11q24.1–q25 in young women with breast cancer: association with poor survival1999In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 80, no 5/6, p. 843-849Article in journal (Refereed)
    Abstract [en]

    Previous 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.

  • 2.
    Johansson, Patrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Fohlin, Helena
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Dufmats, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Nordenskjoeld, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    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 therapy2009In: ACTA ONCOLOGICA, ISSN 0284-186X, Vol. 48, no 4, p. 504-513Article in journal (Refereed)
    Abstract [en]

    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.

  • 3. Lindholm, Christer
    et al.
    Andersson, Ronny
    Dufmats, Monika
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Hansson, Johan
    Ingvar, Christian
    Möller, Torgil
    Sjödin, Helena
    Stierner, Ulrika
    Wagenius, Gunnar
    Invasive cutaneous malignant melanoma in Sweden, 1990-1999: A prospective, population-based study of survival and prognostic factors2004In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 101, no 9, p. 2067-2078Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. 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. METHODS. Twelve thousand five hundred thirty-three patients, which included 97% of all registered melanomas in Sweden, were included and described. Among these, 9515 patients with clinical Stage I and II melanoma were included in an analysis of survival and in a univariate analysis, and 6191 patients were included in a multivariate analysis of prognostic factors. RESULTS. There was no significant change in melanoma incidence during 1990-1999. Favorable prognostic factors were found, especially in younger and female patients, resulting in a relative 5-year survival rate of 91.5%. In the multivariate analysis, significant factors that had a negative effect on survival were Clark level of invasion, Breslow thickness, ulceration, older patient age, trunk location, greatest tumor dimension, nodular histogenetic type, and male gender. CONCLUSIONS. During the period from 1990 to 1999, the 5-year survival of patients with malignant melanoma in Sweden was better compared with the previously reported rates in published, population-based studies from Sweden, probably as a result of better secondary prevention due to better knowledge and awareness by both patients and the medical profession. The more favorable prognostic factors and the change in melanoma location found in younger patients, compared with earlier reports, may reflect changes in clothing as well as tanning habits, however, a decrease also was found in Clark Level II and thin melanomas for the same patient group. The authors concluded that further improvements can be achieved with better access to health care and with the use of early melanoma detection campaigns.

  • 4.
    Myrelid, Pär
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Dufmats, Monika
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Lilja, Ingela
    Grännö, C
    Lannerstad, O
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Atopic manifestations are more common in patients with Crohn disease than in the general population2004In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 39, no 8, p. 731-736Article in journal (Refereed)
    Abstract [en]

    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.

  • 5.
    Rydén, Lisa
    et al.
    Department of Surgery, Helsingborgs Lasarett, Helsingborg, Sweden and Department of Laboratory Medicine, div of Pathology, University Hospital, Malmö.
    Jönsson, Per-Ebbe
    Department of Surgery, Helsingborgs Lasarett, Helsingborg, Sweden.
    Chebil, Gunilla
    Department of Pathology, Helsingborgs Lasarett, Helsingborg.
    Dufmats, Monika
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Fernö, Mårten
    Department of Oncology, University Hospital, Lund.
    Jirström, Karin
    Department of Laboratory Medicine, div of Pathology, University Hospital, Malmö.
    Källström, Ann-Christine
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Landberg, Göran
    Department of Laboratory Medicine, div of Pathology, University Hospital, Malmö.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Thorstenson, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up2005In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 41, no 2, p. 256-264Article in journal (Refereed)
    Abstract [en]

    Adjuvant tamoxifen treatment increases recurrence-free survival (RFS) and overall survival (OS) in early breast cancer, although in premenopausal patients the number of studies comparing tamoxifen vs no treatment are limited. We report herein the effect on RFS of adjuvant tamoxifen treatment in a multicentre trial of premenopausal patients with stage II breast cancer patients randomised between 1986 and 1991 to 2 years of tamoxifen treatment (n = 276) or no treatment (n = 288). The receptor status of the tumour was known for 541 (96%) of the patients included. Tamoxifen treatment significantly increased RFS in patients with hormone receptor-positive (oestrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+)) tumours (Relative Risk (RR) 0.65; 95% Confidence Interval (CI): 0.48–0.89, P = 0.006), and the beneficial effect of tamoxifen was extended to patients with indicators of poor prognosis, such as young age and nodal-positivity. PR status was a significant predictor of response to tamoxifen in multivariate models with testing of interactions of hormone receptor status and adjuvant therapy.

  • 6.
    Sandblom, Gabriel
    et al.
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Dufmats, Monika
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Kerstin
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Prostate carcinoma trends in three counties in Sweden 1987–19962000In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 88, no 6, p. 1445-1453Article in journal (Refereed)
    Abstract [en]

    BACKGROUND 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.

    METHODS The register is based on Swedish personal registration numbers, thereby minimizing the number of dropouts. All cases of prostate carcinoma detected in the southeast region have been recorded according to a defined protocol that has been updated successively to match recent views regarding the disease. To ensure a high number of presented cases, the National Cancer Register was checked for missing cases.

    RESULTS Six thousand seven hundred eighty-two cases of prostate carcinoma were registered in the region between 1987–1996. The age-adjusted incidence rate reached a peak in 1993, followed by a slight decrease. The mean age at diagnosis throughout the period was 74.2 years, with a peak age of 74.8 years in 1992. The number of incidental tumors followed the development of the number of transurethral resections of the prostate performed in the region, with a peak in 1991. The percentage of patients receiving gonadotropin-releasing hormone (GnRH) analogues increased from 3.9% to 37.8% whereas the percentage of patients treated with orchiectomy decreased from 40.0% to 12.8% and the percentage of those treated with radical prostatectomy decreased from 11.1% to 2.5%.

    CONCLUSIONS A diminishing pool of latent tumors may explain the decreasing incidence rate and lower age at diagnosis observed after 1993. Orchiectomy is rapidly being superceded by GnRH analogues. In contrast to trends reported in the U.S., the percentage of men with prostate carcinoma undergoing total prostatectomy appears to be declining in Sweden.

  • 7.
    Sandblom, Gabriel
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Urology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Dufmats, Monika
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Olsson, Mats
    Varenhorst, Eberhard
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Urology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Validity of a population-based cancer register in Sweden - An assessment of data reproducibility in the South-East Region prostate cancer register2003In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 37, no 2, p. 112-119Article in journal (Refereed)
    Abstract [en]

    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 Link÷ping 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 Link÷ping, 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.

  • 8.
    Sandblom, Gabriel
    et al.
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Dufmats, Monika
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Long-term survival in a swedish population-based cohort of men with prostate cancer2000In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 56, no 3, p. 442-447Article in journal (Refereed)
    Abstract [en]

    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.

  • 9. Tejler, G
    et al.
    Norberg, B
    Dufmats, Monika
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Nordenskjöld, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Arnesson, Lars-Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Survival after treatment for breast cancer in a geographically defined population2004In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 91, no 10, p. 1307-1312Article in journal (Refereed)
    Abstract [en]

    Background: South East Sweden with 976000 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. Methods: All patients were reported to a regional cancer registry from which breast cancer incidence, treatment and survival in this defined population were reported. Results: A total of 7892 women had their first invasive breast cancer diagnosed between 1986 and 1999. The median tumour size was 17 mm and 29.9 per cent had axillary metastases. Some 49.8 per cent of these women had a modified radical mastectomy and 31.9 per cent had a segmental resection with axillary clearance. Postoperative radiotherapy was given to 40.3 per cent of the women after mastectomy and to 87.1 per cent after breast-conserving surgery. Tamoxifen and chemotherapy were used as adjuvant treatment except in low-risk patients. Breast cancer-specific survival rate for all stages was 83.5 per cent at 5 years and 74.0 per cent at 10 years. Respective values were 95.8 and 90.9 per cent for patients with stage T1 N0 M0 tumours, and 77.7 and 62.4 per cent for those with T1-2 N1 M0 tumours. Conclusion: Breast specialists treating women with breast cancer according to a joint management programme have achieved very good survival rates.

  • 10.
    Zhang, Hong
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Dufmats, Monika
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    K-ras mutations in colorectal adenocarcinomas and neighbouring transitional mucosa.1998In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 34, no 13, p. 2053-2057Article in journal (Refereed)
    Abstract [en]

    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.

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