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  • 1.
    Aljabery, Firas
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lindblom, Gunnar
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Skoog, Susann
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.2015In: BMC urology, ISSN 1471-2490, Vol. 15, no 1, p. 87-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

  • 2.
    Dahlrot, R. H.
    et al.
    Odense Univ Hosp, Denmark.
    Dowsett, J.
    Odense Univ Hosp, Denmark.
    Fosmark, S.
    Odense Univ Hosp, Denmark.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Henriksson, R.
    Umea Univ, Sweden; Reg Canc Ctr Stockholm Gotland, Sweden.
    Boldt, H.
    Odense Univ Hosp, Denmark.
    de Stricker, K.
    Odense Univ Hosp, Denmark.
    Sorensen, M. D.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Poulsen, H. S.
    Rigshosp, Denmark.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Hansen, S.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Kristensen, B. W.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis2018In: Neuropathology and Applied Neurobiology, ISSN 0305-1846, E-ISSN 1365-2990, Vol. 44, no 2, p. 172-184Article in journal (Refereed)
    Abstract [en]

    Aims: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status. Methods: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population-based Region of Southern Denmark (RSD)cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM-patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules. Results: When divided at the median, patients with low expression of MGMT protein (AF-low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS-cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF-low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF-low had the best outcome; median OS 23.1 and 20.0 months, respectively. Conclusion: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour-specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.

  • 3.
    El Ouali, Mourad
    et al.
    University of Kiel, Germany.
    Fohlin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Medicine and Health Sciences.
    Srivastav, Anand
    University of Kiel, Germany.
    An approximation algorithm for the partial vertex cover problem in hypergraphs2016In: Journal of combinatorial optimization, ISSN 1382-6905, E-ISSN 1573-2886, Vol. 31, no 2, p. 846-864Article in journal (Refereed)
    Abstract [en]

    Let be a hypergraph with set of vertices and set of (hyper-)edges . Let be the maximum size of an edge, be the maximum vertex degree and be the maximum edge degree. The -partial vertex cover problem in hypergraphs is the problem of finding a minimum cardinality subset of vertices in which at least hyperedges are incident. For the case of and constant it known that an approximation ratio better than cannot be achieved in polynomial time under the unique games conjecture (UGC) (Khot and Ragev J Comput Syst Sci, 74(3):335-349, 2008), but an -approximation ratio can be proved for arbitrary (Gandhi et al. J Algorithms, 53(1):55-84, 2004). The open problem in this context has been to give an -ratio approximation with , as small as possible, for interesting classes of hypergraphs. In this paper we present a randomized polynomial-time approximation algorithm which not only achieves this goal, but whose analysis exhibits approximation phenomena for hypergraphs with not visible in graphs: if and are constant, and , we prove for -uniform hypergraphs a ratio of , which tends to the optimal ratio 1 as tends to . For the larger class of hypergraphs where , is not constant, but is a constant, we show a ratio of . Finally for hypergraphs with non-constant , but constant , we get a ratio of for , leaving open the problem of finding such an approximation for k &lt; m/4(.)

  • 4.
    Frödin, Ulla
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Fomichov, Victoria
    Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Juliusson, G.
    Lund University, Sweden; Lund University, Sweden.
    Börjeson, Sussanne
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Frequent and long-term follow-up of health-related quality of life following allogeneic haematopoietic stem cell transplantation2015In: European Journal of Cancer Care, ISSN 0961-5423, E-ISSN 1365-2354, Vol. 24, no 6, p. 898-910Article in journal (Refereed)
    Abstract [en]

    Health-related quality of life (HRQL) was evaluated in 94 patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) after myeloablative (MAC, n=18) or reduced intensity conditioning (RIC, n=76). HRQL was assessed with the EORTC QLQ C-30 during the inpatient period as well as during the following 3years, i.e. at baseline and 12 times thereafter. Functional status and global quality of life decreased from baseline to weeks 2 and 3, especially role and social functions. Symptoms increased significantly during the first 3weeks, particularly appetite loss, nausea and vomiting, diarrhoea and fatigue. It took at least 1year for HRQL to return to the baseline level. The only function that improved significantly 3years after HSCT was role function. Patients treated with MAC experienced significantly worse HRQL at baseline than patients treated with RIC, as well as more pain, sleep disturbance and appetite loss in weeks 3 and 4. Patients with extensive chronic graft-versus-host disease experienced reduced HRQL. These results provide a clinically useful overview of patients HRQL during and after HSCT and indicate when they require increased support. The results demonstrate the importance of close follow-ups during the first year after HSCT to improve preventive or supportive interventions.

  • 5.
    Heedman, P. A.
    et al.
    Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Palliat Educ and Research Centre, Sweden.
    Canslatt, E.
    Lanssjukhuset Kalmar, Sweden.
    Henriks, G.
    Jonköping County Council, Sweden.
    Starkhammar, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Fomichov, Victoria
    Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Variation at presentation among colon cancer patients with metastases: a population-based study2015In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 17, no 5, p. 403-408Article in journal (Refereed)
    Abstract [en]

    AimThe study aimed to describe and follow a 2year cohort of colon cancer patients with Stage IV disease from presentation to long-term outcome. MethodThe records of 177 colon cancer patients diagnosed in southeast Sweden during 2009-2010 with disseminated disease at presentation were reviewed retrospectively. ResultsThe patients were heterogeneous with respect to age, performance status and survival. Despite metastatic disease, local symptoms from the primary tumour dominated the initial clinical picture. Forty-one per cent had anaemia. The time from suspicion of colon cancer to established diagnosis of disseminated disease varied from 0 to 231days (emergency cases included, median 12days). The majority (77%) were diagnosed in hospital. In 53% the primary tumour and the metastases were not diagnosed on the same occasion which may increase the risk for misinformation or delays in the care process. The possibility of simultaneous diagnosis was doubled when the patient was investigated as an inpatient. Patients were seen by one to 12 physicians (median three) in the investigation phase, and one to 47 (median 11) from diagnosis until the last record in the hospital notes. The 1-year survival was 46%. ConclusionPatients with metastatic colon cancer at presentation are heterogeneous and warrant an adapted multidisciplinary approach to achieve the goal of individualized treatment for each patient in accordance with the Swedish national cancer strategy.

  • 6.
    Jahnson, Staffan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Hosseini Aliabad, Abolfazl
    Karolinska University Hospital, Sweden.
    Holmang, Sten
    Sahlgrens University Hospital, Sweden.
    Jancke, Georg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Liedberg, Fredrik
    Skåne University Hospital, Sweden.
    Ljungberg, Borje
    Northern University Hospital, Sweden.
    Malmstrom, Per-Uno
    University of Uppsala Hospital, Sweden.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Medicine and Health Sciences.
    Swedish National Registry of Urinary Bladder Cancer: No difference in relative survival over time despite more aggressive treatment2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 1, p. 14-20Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to use the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) to investigate changes in patient and tumour characteristics, management and survival in bladder cancer cases over a period of 15 years. Materials and methods. All patients with newly detected bladder cancer reported to the SNRUBC during 1997-2011 were included in the study. The cohort was divided into three groups, each representing 5 years of the 15 year study period. Results. The study included 31,266 patients (74% men, 26% women) with a mean age of 72 years. Mean age was 71.7 years in the first subperiod (1997-2001) and 72.5 years in the last subperiod (2007-2011). Clinical T categorization changed from the first to the last subperiod: Ta from 45% to 48%, T1 from 21.6% to 22.4%, and T2-T4 from 27% to 25%. Also from the first to the last subperiod, intravesical treatment after transurethral resection for T1G2 and T1G3 tumours increased from 15% to 40% and from 30% to 50%, respectively, and cystectomy for T2-T4 tumours increased from 30% to 40%. No differences between the analysed subperiods were found regarding relative survival in patients with T1 or T2-T4 tumours, or in the whole cohort. Conclusions. This investigation based on a national bladder cancer registry showed that the age of the patients at diagnosis increased, and the proportion of muscle-invasive tumours decreased. The treatment of all tumour stages became more aggressive but relative survival showed no statistically significant change over time.

  • 7.
    Jancke, Georg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Medicine and Health Sciences.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Tumour location adjacent to the ureteric orifice in primary Ta/T1 bladder cancer is predictive of recurrence2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 1, p. 33-38Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to evaluate tumour growth located around the ureteric orifice (LUO) at primary diagnosis of Ta/T1 urinary bladder cancer in relation to effects on recurrence and progression. Materials and methods: Clinical and pathological characteristics of patients diagnosed with primary Ta/T1 urinary bladder cancer from 1992 to 2007 were recorded prospectively. Location of the primary tumour and growth around the ureteric orifice (within 1 cm) were recorded and correlated with recurrence and progression during further follow-up. Hazard ratios (HRs) were estimated using Cox regression with 95% confidence intervals (CIs) in both univariate and multivariate analysis. Results: The study included 768 evaluable patients with a median follow-up of 60 months. Recurrence was observed in 478 patients (62%) and progression in 71 (9%). Growth of a primary tumour adjacent to the ureteric orifice was associated with recurrence (HR = 1.28, 95% CI = 1.07-1.54) but not progression (HR = 1.04, 95% CI = 0.65-1.67). The most common location of the first recurrence was the posterior bladder wall (29%). Other locations in the bladder did not predict recurrence or progression. Additional factors affecting recurrence were tumour size greater than 15mm, T1 tumour category, multiplicity, malignant or missing/not representative bladder wash cytology and surgery performed by residents. Conclusions: A primary tumour located around the ureteric orifice was predictive of recurrence, which could be taken into account in future follow-up schedules.

  • 8.
    Johansson, Henrik J
    et al.
    Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, SE-171 65 Stockholm, Sweden.
    Sanchez, Betzabe C
    Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, SE-171 65 Stockholm, Sweden.
    Forshed, Jenny
    Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, SE-171 65 Stockholm, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Health Sciences.
    Fohlin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Health Sciences.
    Lewensohn, Rolf
    Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden.
    Hall, Per
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, Stockholm, 17177 Sweden.
    Bergh, Jonas
    Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, SE-171 65 Stockholm, Sweden.
    Lehtiö, Janne
    Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, SE-171 65 Stockholm, Sweden.
    Linderholm, Barbro K
    Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, SE-171 65 Stockholm, Sweden // Department of Oncology, Sahlgrenska Academy and University Hospital, SE-413 45 Gothenburg, Sweden.
    Proteomics profiling identify CAPS as a potential predictive marker of tamoxifen resistance in estrogen receptor positive breast cancer2015In: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 12, no 1, p. 8-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Despite the success of tamoxifen since its introduction, about one-third of patients with estrogen (ER) and/or progesterone receptor (PgR) - positive breast cancer (BC) do not benefit from therapy. Here, we aim to identify molecular mechanisms and protein biomarkers involved in tamoxifen resistance.

    RESULTS: Using iTRAQ and Immobilized pH gradient-isoelectric focusing (IPG-IEF) mass spectrometry based proteomics we compared tumors from 12 patients with early relapses (<2 years) and 12 responsive to therapy (relapse-free > 7 years). A panel of 13 proteins (TCEAL4, AZGP1, S100A10, ALDH6A1, AHNAK, FBP1, S100A4, HSP90AB1, PDXK, GFPT1, RAB21, MX1, CAPS) from the 3101 identified proteins, potentially separate relapse from non-relapse BC patients. The proteins in the panel are involved in processes such as calcium (Ca(2+)) signaling, metabolism, epithelial mesenchymal transition (EMT), metastasis and invasion. Validation of the highest expressed proteins in the relapse group identify high tumor levels of CAPS as predictive of tamoxifen response in a patient cohort receiving tamoxifen as only adjuvant therapy.

    CONCLUSIONS: This data implicate CAPS in tamoxifen resistance and as a potential predictive marker.

  • 9.
    Klaff, Rami
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Faculty of Medicine and Health Sciences.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Medicine and Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Sandblom, Gabriel
    Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Hospital, Huddinge, Sweden.
    The Long-term Disease-specific Mortality of Low-risk Localized Prostate Cancer: A Prospective Population-based Register Study Over Two Decades2016In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 91, p. 77-82Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To identify prognostic factors, and to estimate the long-term disease-specific and annual disease-specific mortality rates of low-risk prostate cancer patients from the early prostate-specific antigen (PSA) era. PATIENTS AND METHODS We studied data extracted from the Southeast Region Prostate Cancer Register in Sweden, on 1300 patients with clinically localized low-risk tumors, T1-2, PSA level amp;lt;= 10 mu g/L and Gleason scores 2-6 or World Health Organization Grade 1, diagnosed 1992-2003. The Cox multivariate regression model was used to evaluate factors predicting survival. Prostate cancer death rates per 1000 person-years were estimated for 4 consecutive follow-up time periods: 0-5, 5-10, 10-15, and 15+ years after diagnosis. RESULTS During the follow-up of overall survivors (mean 10.6 years; maximum 21.8 years), 93 patients (7%) died of prostate cancer. Cancer-specific survival was 0.98 (95% confidence interval [CI] 0.97-0.99), 0.95 (95% CI 0.93-0.96), 0.89 (95% CI 0.86-0.91), and 0.84 (95% CI 0.80-0.88), 5, 10, 15, and 20 years after diagnosis. The 5-year increases in cancer-specific mortality were statistically significant (P amp;lt;. 001). Patients with PSA amp;gt;= 4 mu g/L managed initially with watchful waiting and those aged 70 years or older had a significantly higher risk of dying from their prostate cancer. CONCLUSION The long-term disease-specific mortality of low-risk localized prostate cancer is low, but the annual mortality rate from prostate cancer gradually increases. This indicates that some tumors slowly develop into lethal cancer, particularly in patients 70 years or older with a PSA level amp;gt;= 4 mu g/L. (C) 2016 Elsevier Inc.

  • 10.
    Krynitz, Britta
    et al.
    Karolinska University of Labs, Sweden; Karolinska University, Sweden.
    Lundh Rozell, Barbro
    Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lyth, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Smedby, Karin E.
    Karolinska University Hospital, Sweden.
    Lindelof, Bernt
    Karolinska University, Sweden; Karolinska University, Sweden.
    Cutaneous malignant melanoma in the Swedish organ transplantation cohort: A study of clinicopathological characteristics and mortality2015In: The Journal of American Academy of Dermatology, ISSN 0190-9622, E-ISSN 1097-6787, Vol. 73, no 1, p. 106-U190Article in journal (Refereed)
    Abstract [en]

    Background: Risk of cutaneous melanoma is increased among organ transplant recipients (OTRs) but outcome has rarely been evaluated. Objective: We sought to assess melanoma characteristics and prognosis among OTRs versus the general population. Methods: Using Swedish health care registers, we identified melanomas in OTRs (n = 49) and in the general population (n = 22,496), given a diagnosis between 1984 and 2008 and followed up through December 31, 2012. Tumor slides of posttransplantation melanomas were reviewed. Odds ratios for comparison of histopathological characteristics and hazard ratios of melanoma-specific death were calculated. Results: Among OTRs the trunk was the most common anatomic melanoma site (50% among female vs 51% among male) and 73% (n = 36) of all melanomas were histologically associated with a melanocytic nevus, 63% (n = 31) atypical/dysplastic. Compared with population melanomas, posttransplantation melanomas were more advanced at diagnosis (Clark level III-V: odds ratio 2.2 [95% confidence interval 1.01-4.7, P = .03], clinical stages III-IV: odds ratio 4.2 [1.6-10.8, P = .003]). Risk of melanoma-specific death was increased among OTRs: adjusted hazard ratio 3.0 (1.7-5.3, P = .0002). Limitations: Only posttransplantation melanoma slides were reviewed. Conclusions: Melanomas were more advanced at diagnosis and melanoma-specific survival was poorer in OTRs than in the general population. Prophylactic excision of truncal nevi among OTRs may be advised.

  • 11.
    Loftås, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Fomichov Casaballe, Victoria
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Nodal involvement in luminal complete response after neoadjuvant treatment for rectal cancer2016In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 42, no 6, p. 801-807Article in journal (Refereed)
    Abstract [en]

    Background: Pathological complete response (pCR) after neoadjuvant therapy in rectal cancer is correlated with improved survival. There is limited knowledge on the incidence of pCR at a national level with uniform guidelines. The aim of this prospective register-based study was to investigate the incidence and outcome of pCR in relation to neoadjuvant therapy in a national cohort. Method: All patients abdominally operated for rectal cancer between 2007 and 2012 (n = 7885) were selected from The Swedish Colorectal Cancer Register. Twenty-six per cent (n = 2063) had neoadjuvant therapy with either long or short course radiotherapy with amp;gt;4 weeks delay with the potential to achieve pCR. The primary endpoints were pCR and survival in relation to neoadjuvant therapy. Results: Complete eradication of the luminal tumor, ypTO was found in 161 patients (8%). In 83% of the ypTO the regional lymph nodes were tumor negative (ypTONO), 12% had 1-3 positive lymph nodes (ypTON1) and 4% had more than three positive lymph nodes (ypTON2). There was significantly greater survival with ypTO compared to ypT+ (hazard ratio 0.38 (C.I 0.25-0.58)) and survival was significantly greater in patients with ypTONO compared to ypT0N1-2 (hazard ratio 0.36 (C.I 0.15-0.86)). In ypTO, cT3-4 tumors had the greater risk of node-positivity. The added use of chemotherapy resulted in 10% ypTO compared to 5.1% in the group without chemotherapy (p amp;lt; 0.00004). Conclusion: Luminal pathological complete response occurred in 8%, 16% of them had tumor positive nodes. The survival benefit of luminal complete response is dependent upon nodal involvement status. (C) 2016 Elsevier Ltd. All rights reserved.

  • 12.
    Loorents, Vera
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rosell, Johan
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Salgado Willner, Helen
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Börjeson, Sussanne
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Health-related quality of life up to 1 year after radiotherapy in patients with head and neck cancer (HNC)2016In: SpringerPlus, E-ISSN 2193-1801, Vol. 5, no 1, article id 669Article in journal (Refereed)
    Abstract [en]

    Background

    Detailed symptom specific descriptions of health-related quality of life (HRQOL), using validated questionnaires in patients with head and neck cancer (HNC) are sparse. The aim of the present study was to investigate HRQOL in patients with HNC up to 1 year after radiotherapy (RT), using two standardised questionnaires.

    Methods

    The data for the present study was originally collected in a randomised, prospective study. Forty-seven patients from two RT clinics in Sweden were included to investigate the secondary aim: HRQOL. Data was recorded at baseline, completion of RT, and 3, 6, 12 months after completed RT, using the questionnaire EORTC QLQ-C30-version 3 and the disease-specific module EORTC QLQ-H&N35.

    Results

    Most symptoms and functions deteriorated significantly by the end of RT, improved gradually by 3 and 6 months and reached baseline levels at 12 months after completed RT. However, 1 year after completed RT there were remaining significant problems in senses, dry mouth and sticky saliva.

    Conclusions

    Radiation therapy affects health-related quality of life in patients with head and neck cancer, both in the short and long term. Caregivers need management strategies for early detection and treatment of specific problems throughout the treatment period to help in the prevention of long-term symptoms.

  • 13.
    Lyth, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Faculty of Medicine and Health Sciences.
    Mikiver, R.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Nielsen, K.
    Lund University, Sweden.
    Isaksson, K.
    Lund University, Sweden.
    Ingvar, C.
    Lund University, Sweden.
    Prognostic instrument for survival outcome in melanoma patients: based on data from the population-based Swedish Melanoma Register2016In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 59, p. 171-178Article in journal (Refereed)
    Abstract [en]

    Background: Several major analyses have identified a consistent set of independent risk factors for cutaneous malignant melanoma (CMM). A few prognostic models have been presented but some are based on a limited number of patients and others are based on selected groups of patients referred to major institutions. No nationwide population-based prognostic instrument for survival of CMM has been presented. The Swedish Melanoma Register (SMR) database covers 99% of CMM diagnosed in Sweden and includes today &gt;50,000 cases. Objectives: To create a prognostic instrument based on SMR data to give highly reliable risk profiles for patients diagnosed with localised CMM. Methods: Clinicopathological data were linked to the cause of death registry for calculation of CMM-specific survival. A generalised gamma method was used to derive 1, 5 and 10year probabilities of death for each combination of patient and tumour data: age, sex, tumour site, tumour thickness, tumour ulceration, Clarks level of invasion and when applicable also outcome of sentinel node biopsy (SNB). Results: Tumour thickness had the highest prognostic impact, explaining 77% of the model. Women had 30% lower risk of death because of CMM than men. Presence of ulceration nearly doubled the risk. If the patient had a positive SNB status the risk of death due to CMM increased three times versus a negative SNB status. Conclusion: This unique population-based prognostic model for primary CMM shows better survival than the American Joint Commission on Cancer prognostic model widely used. The reason is probably that the referral bias is eliminated in a population-based cohort.

  • 14.
    Nordenskjold, A. E.
    et al.
    Southern Alvsborg Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Fohlin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Medicine and Health Sciences. Regional Cancer Centre South East Sweden, Linkoping, Sweden.
    Albertsson, P.
    Sahlgrens University Hospital, Sweden.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Chamalidou, C.
    Southern Alvsborg Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Einbeigi, Z.
    Sahlgrens University Hospital, Sweden.
    Holmberg, E.
    Regional Cancer Centre, Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Karlsson, P.
    Sahlgrens University Hospital, Sweden.
    No clear effect of postoperative radiotherapy on survival of breast cancer patients with one to three positive nodes: a population-based study2015In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, no 6, p. 1149-1154Article in journal (Refereed)
    Abstract [en]

    Background: In published radiotherapy trials, the failure rate in the control arm among patients with one to three positive nodes is high compared with that seen with modern adjuvant treatments. Therefore, the generalizability of the results has been questioned. The aim of the present study was to compare relative survival in breast cancer patients between two Swedish regions with screening mammography programs and adjuvant treatment guidelines similar with the exception of the indication of radiotherapy for patients with one to three positive nodes. Patients and methods: Between 1989 and 2006, breast cancer patients were managed very similarly in the west and southeast regions, except for indication for postoperative radiotherapy. In patients with one to three positive nodes, post-mastectomy radiotherapy was generally given in the southeast region (89% of all cases) and generally not given in the west region (15% of all cases). For patients with one to three positive nodes who underwent breast-conserving surgery, patients in the west region had breast radiotherapy only, while patients in the southeast region had both breast and lymph nodes irradiated. Results: The 10-year relative survival for patients with one to three positive lymph nodes was 78% in the west region and 77% in the southeast region (P = 0.12). Separate analyses depending on type of surgery, as well as number of examined nodes, also revealed similar relative survival. Conclusion: Locoregional postoperative radiotherapy has well-known side-effects, but in this population-based study, there was little or no influence of this type of radiotherapy on survival when one to three lymph nodes were involved.

  • 15.
    Nordenskjold, Anna
    et al.
    Sahlgrens Acad, Sweden; Southern Alvsborg Hospital, Sweden.
    Fohlin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Fornander, Tommy
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden; Regional Cancer Centre Stockholm Gotland, Sweden.
    Lofdahl, Britta
    St Göran Hospital, Sweden.
    Skoog, Lambert
    Karolinska University Hospital, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Progesterone receptor positivity is a predictor of long-term benefit from adjuvant tamoxifen treatment of estrogen receptor positive breast cancer2016In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 160, no 2, p. 313-322Article in journal (Refereed)
    Abstract [en]

    The independent predictive information from progesterone receptor (PgR) positivity for breast cancer treated with tamoxifen has been questioned after an overview by the Early Breast Cancer Trialists Collaborative Group (EBCTCG). However, the studies in the overview were to a large content performed before modern PgR immunohistochemistry (IHC) was developed. We therefore investigated the predictive value of PgR determined with IHC in estrogen receptor (ER)-positive tumors from patients participating in the Stockholm trial of adjuvant tamoxifen therapy. The Stockholm Breast Cancer Study Group conducted a randomized trial during 1976 through 1990 comparing adjuvant tamoxifen versus control. The patients were stratified according to tumor size and lymph node status in high-risk and low-risk groups. In this study, we evaluated 618 patients with ER-positive "low-risk" breast cancer (size aecurrency sign 30 mm, lymph node-negative) for whom PgR was determined by IHC at one pathology laboratory. The median time of follow-up was 21 years. Patients with ER-positive tumors that were also PgR-positive by IHC did benefit from tamoxifen, while we could not show any long-term benefit for those with tumors positive for ER only (recurrence rate ratio 0.43, 95 % CI 0.29-0.62 and 0.87, 95 % CI 0.52-1.46, respectively). We further investigated the influence of different levels of PgR positivity on recurrence risk. The results show that at all receptor levels with aeyen10 % stained PgR-positive cells, the patients did benefit from tamoxifen. There was no clear linear trend in benefit with increasing proportion of stained cells. PgR positivity determined by IHC is a marker indicating long-term benefit from adjuvant tamoxifen in patients with ER-positive tumors.

  • 16.
    Patschan, Oliver
    et al.
    Skåne University Hospital, Sweden.
    Holmang, Sten
    Sahlgrens University Hospital, Sweden.
    Hosseini, Abolfazl
    Karolinska University Hospital, Sweden.
    Liedberg, Fredrik
    Skåne University Hospital, Sweden.
    Ljungberg, Borje
    Northern University Hospital, Sweden.
    Malmstrom, Per-Uno
    Akad University Hospital, Sweden.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Use of bacillus Calmette-Guerin in stage T1 bladder cancer: Long-term observation of a population-based cohort2015In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, no 2, p. 127-132Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to analyse the rate of use of bacillus Calmette-Guerin (BCG) at a population-based level, and the overall mortality and bladder cancer mortality due to stage T1 bladder cancer in a national, population-based register. Materials and methods. In total, 3758 patients with primary stage T1 bladder cancer, registered in the Swedish Bladder Cancer Register between 1997 and 2006, were included. Age, gender, tumour grade and primary treatment in the first 3-6 months were registered. High-volume hospitals registered 10 or more T1 tumours per year. Date and cause of death were obtained from the National Board of Health and Welfare Cause of Death Register. Results. BCG was given to 896 patients (24%). The use of BCG increased from 18% between 1997 and 2000, to 24% between 2001 and 2003, and to 31% between 2004 and 2006. BCG was given more often to patients with G3 tumours, patients younger than 75 years and patients attending high-volume hospitals. BCG treatment, grade 2 tumours and patient age younger than 75 years were associated with lower mortality due to bladder cancer. Hospital volume, gender and year of diagnosis were not related to bladder cancer mortality. However, selection factors might have affected the results since comorbidity, number of tumours and tumour size were unknown. Conclusions. Intravesical BCG is underused at a population-based level in stage T1 bladder cancer in Sweden, particularly in patients 75 years or older, and in those treated at low-volume hospitals. BCG should be offered more frequently to patients with stage T1 bladder cancer in Sweden.

  • 17.
    Roodakker, Kenney R.
    et al.
    Uppsala University, Sweden.
    Elsir, Tamador
    Uppsala University, Sweden; Karolinska Institute, Sweden.
    Edqvist, Per-Henrik D.
    Uppsala University, Sweden.
    Hagerstrand, Daniel
    Karolinska Institute, Sweden.
    Carison, Joseph
    Karolinska Institute, Sweden.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Henriksson, Roger
    Umeå University, Sweden; Regional Cancer Centre, Sweden.
    Ponten, Fredrik
    Uppsala University, Sweden.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Stupp, Roger
    University of Zurich Hospital, Switzerland.
    Tchougounova, Elena
    Uppsala University, Sweden.
    Nister, Monica
    Karolinska Institute, Sweden.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Smits, Anja
    Uppsala University, Sweden; University of Gothenburg, Sweden.
    PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 45, p. 72431-72442Article in journal (Refereed)
    Abstract [en]

    PROX1 is a transcription factor with an essential role in embryonic development and determination of cell fate. In addition, PROX1 has been ascribed suppressive as well as oncogenic roles in several human cancers, including brain tumors. In this study we explored the correlation between PROX1 expression and patient survival in high-grade astrocytomas. For this purpose, we analyzed protein expression in tissue microarrays of tumor samples stratified by patient age and IDH mutation status. We initially screened 86 unselected high-grade astrocytomas, followed by 174 IDH1-R132H1 immunonegative glioblastomas derived from patients aged 60 years and older enrolled in the Nordic phase III trial of elderly patients with newly diagnosed glioblastoma. Representing the younger population of glioblastomas, we studied 80 IDH-wildtype glioblastomas from patients aged 18-60 years. There was no correlation between PROX1 protein and survival for patients with primary glioblastomas included in these cohorts. In contrast, high expression of PROX1 protein predicted shorter survival in the group of patients with IDH-mutant anaplastic astrocytomas and secondary glioblastomas. The prognostic impact of PROX1 in IDH-mutant 1p19q non-codeleted high-grade astrocytomas, as well as the negative findings in primary glioblastomas, was corroborated by gene expression data extracted from the Cancer Genome Atlas. We conclude that PROX1 is a new prognostic biomarker for 1p19q non-codeleted high-grade astrocytomas that have progressed from pre-existing lowgrade tumors and harbor IDH mutations.

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