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  • 151.
    Johansson, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Steineck, Gunnar
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Can radical prostatectomy prevent and improve lower urinary tract symptoms?2008Ingår i: Nature clinical practice. Urology, ISSN 1743-4270, Vol. 5, nr 6, s. 304-5Artikel i tidskrift (Refereegranskat)
  • 152.
    Johansson, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Steineck, Gunnar
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Division of Cancer Studies, Medical School, King's College London, London, UK.
    Johansson, Jan-Erik
    Nyberg, Tommy
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Quality of Life after Radical Prostatectomy or Watchful Waiting With or Without Androgen Deprivation Therapy: The SPCG-4 Randomized Trial2018Ingår i: European Association of Urology, Vol. 1, nr 2, s. 134-142Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Men with prostate cancer experience adjuvant androgen deprivation therapy (ADT) differently.

    Objective

    To evaluate the effect of ADT on quality of life (QoL), patients’ experience of clinical check-ups, and differences in cancer information as explanatory factors.

    Design, setting, and participants

    A study-specific questionnaire was sent to all men randomized in the SPCG-4 trial to radical prostatectomy (RP) or watchful waiting (WW) still alive (400/695) and a control group of 281 men.

    Intervention

    ADT.

    Outcome measurements and statistical analysis

    Self-assessed QoL, worry at clinical check-ups, and amount of information received. Estimated relative risks with associated 95% confidence intervals (CI) for risk comparisons between groups using a log-binomial regression.

    Results and limitations

    The SPCG-4 men had median follow-up of 12.2 yr and median age of 77.0 yr; 26% in the RP group and 40% in the WW group received ADT treatment. High QoL for men without ADT was 36% for the RP group, 44% for the WW group, and 45% for the control group. High QoL for men with ADT was 30% for the RP group and 20% for the WW group. Among men with ADT, those in the WW group received significantly less information about the disease than men in the RP group. Receiving no or little information about prostate cancer was reported by 17% of patients in the RP group and 39% in the WW group among men receiving ADT (relative risk 0.44, 95% CI 0.22–0.89). At clinical check-ups, men treated with ADT had significantly higher levels of worry, regardless of study group, than men without ADT. Limitations include the lack of longitudinal data and a low number of men receiving ADT in the RP group.

    Conclusions

    Men on WW without ADT reported high QoL comparable to that for men without prostate cancer. ADT treatment in the WW group was associated with the lowest scores for all psychological parameters, and these men reported that they were least informed about prostate cancer and its consequences.

    Patient summary

    Good communication and information from caregivers are associated with less negative psychological effects at prostate cancer progression.

  • 153.
    Johansson, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Steineck, Gunnar
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Johansson, Jan-Erik
    Nyberg, Tommy
    Ruutu, Mirja
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial.2011Ingår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 12, nr 9, s. 891-899Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years. METHODS: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint. FINDINGS: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7-17) and a median age of 77·0 years (range 61-88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07-1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life. INTERPRETATION: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information. FUNDING: US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér.

  • 154. Jonsson, Pär
    et al.
    Wuolikainen, Anna
    Thysell, Elin
    Chorell, Elin
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ Hosp, Dept Surg & Perioperat Sci, Urol & Androl, S-90187 Umeå, Sweden.
    Wikström, Pernilla
    Antti, Henrik
    Constrained randomization and multivariate effect projections improve information extraction and biomarker pattern discovery in metabolomics studies involving dependent samples.2015Ingår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 11, nr 6, s. 1667-1678Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Analytical drift is a major source of bias in mass spectrometry based metabolomics confounding interpretation and biomarker detection. So far, standard protocols for sample and data analysis have not been able to fully resolve this. We present a combined approach for minimizing the influence of analytical drift on multivariate comparisons of matched or dependent samples in mass spectrometry based metabolomics studies. The approach is building on a randomization procedure for sample run order, constrained to independent randomizations between and within dependent sample pairs (e.g. pre/post intervention). This is followed by a novel multivariate statistical analysis strategy allowing paired or dependent analyses of individual effects named OPLS-effect projections (OPLS-EP). We show, using simulated data that OPLS-EP gives improved interpretation over existing methods and that constrained randomization of sample run order in combination with an appropriate dependent statistical test increase the accuracy and sensitivity and decrease the false omission rate in biomarker detection. We verify these findings and prove the strength of the suggested approach in a clinical data set consisting of LC/MS data of blood plasma samples from patients before and after radical prostatectomy. Here OPLS-EP compared to traditional (independent) OPLS-discriminant analysis (OPLS-DA) on constrained randomized data gives a less complex model (3 versus 5 components) as well a higher predictive ability (Q2 = 0.80 versus Q2 = 0.55). We explain this by showing that paired statistical analysis detects 37 unique significant metabolites that were masked for the independent test due to bias, including analytical drift and inter-individual variation.

  • 155. Kaasinen, Eero
    et al.
    Wijkström, Hans
    Rintala, Erkki
    Mestad, Oddvar
    Jahnson, Staffan
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Seventeen-year follow-up of the prospective randomized Nordic CIS study: BCG monotherapy versus alternating therapy with mitomycin C and BCG in patients with carcinoma in situ of the urinary bladder2016Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, nr 5, s. 360-368Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of this study was to compare the long-term efficacy of BCG monotherapy to alternating therapy of mitomycin C (MMC) and BCG in patients with carcinoma in situ (CIS).

    MATERIALS AND METHODS: Between 1992 and 1997, 321 patients with CIS were randomized from Finland, Norway and Sweden in a prospective multicenter trial into two treatment groups. The alternating therapy comprised six weekly instillations of MMC 40 mg followed by 10 instillations of BCG (Connaught 120 mg) or MMC alternating monthly for 1 year. BCG monotherapy followed the same 6 + 10 schedule. Stratification was done by nationality and CIS category. Primary endpoints were time to first recurrence and time to progression. Secondary endpoints were disease-specific mortality and overall survival. The main statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model with the cumulative incidence and Kaplan-Meier analyses.

    RESULTS: The median follow-up time was 9.9 years (maximum 19.9 years) in the BCG group and 8.9 years (maximum 20.3 years) in the alternating group. The risk of recurrence was significantly lower in the BCG group than in the alternating group (49 vs 59% at 15 years, respectively; hazard ratio 0.74, 95% confidence interval 0.54-1.00, p = 0.048). There were no significant differences in the other endpoints. Patients who progressed after 2 years were particularly prone to dying from bladder carcinoma. Younger patients performed worse than older ones.

    CONCLUSIONS: BCG monotherapy including monthly maintenance was effective and better than the alternating therapy. The risk of dying from bladder carcinoma after progression was high.

  • 156. Kamat, Ashish M
    et al.
    Hahn, Noah M
    Efstathiou, Jason A
    Lerner, Seth P
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Choi, Woonyoung
    Guo, Charles C
    Lotan, Yair
    Kassouf, Wassim
    Bladder cancer2016Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, nr 10061, s. 2796-2810Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Bladder cancer is a complex disease associated with high morbidity and mortality rates if not treated optimally. Awareness of haematuria as the major presenting symptom is paramount, and early diagnosis with individualised treatment and follow-up is the key to a successful outcome. For non-muscle-invasive bladder cancer, the mainstay of treatment is complete resection of the tumour followed by induction and maintenance immunotherapy with intravesical BCG vaccine or intravesical chemotherapy. For muscle-invasive bladder cancer, multimodal treatment involving radical cystectomy with neoadjuvant chemotherapy offers the best chance for cure. Selected patients with muscle-invasive tumours can be offered bladder-sparing trimodality treatment consisting of transurethral resection with chemoradiation. Advanced disease is best treated with systemic cisplatin-based chemotherapy; immunotherapy is emerging as a viable salvage treatment for patients in whom first-line chemotherapy cannot control the disease. Developments in the past 2 years have shed light on genetic subtypes of bladder cancer that might differ from one another in response to various treatments.

  • 157.
    Kinsella, Netty
    et al.
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.;Royal Marsden Hosp, Dept Urol, London, England..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Cahill, Declan
    Royal Marsden Hosp, Dept Urol, London, England..
    Brown, Christian
    Kings Coll Hosp London, Dept Urol, London, England..
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bratt, Ola
    Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Carlsson, Sigrid
    Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden.;Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA..
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.;Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Factors Influencing Men's Choice of and Adherence to Active Surveillance for Low-risk Prostate Cancer: A Mixed-method Systematic Review2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 3, s. 261-280Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Context: Despite support for active surveillance (AS) as a first treatment choice for men with low-risk prostate cancer (PC), this strategy is largely underutilised.

    Objective: To systematically review barriers and facilitators to selecting and adhering to AS for low-risk PC.

    Evidence acquisition: We searched PsychINFO, PubMed, Medline 2000-now, Embase, CINAHL, and Cochrane Central databases between 2002 and 2017 using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The Purpose, Respondents, Explanation, Findings and Significance (PREFS) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) quality criteria were applied. Forty-seven studies were identified.

    Evidence synthesis: Key themes emerged as factors influencing both choice and adherence to AS: (1) patient and tumour factors (age, comorbidities, knowledge, education, socioeconomic status, family history, grade, tumour volume, and fear of progression/side effects); (2) family and social support; (3) provider (speciality, communication, and attitudes); (4) healthcare organisation (geography and type of practice); and (5) health policy (guidelines, year, and awareness).

    Conclusions: Many factors influence men's choice and adherence to AS on multiple levels. It is important to learn from the experience of other chronic health conditions as well as from institutions/countries that are making significant headway in appropriately recruiting men to AS protocols, through standardised patient information, clinician education, and nationally agreed guidelines, to ultimately decrease heterogeneity in AS practice.

    Patient summary: We reviewed the scientific literature for factors affecting men's choice and adherence to active surveillance (AS) for low-risk prostate cancer. Our findings suggest that the use of AS could be increased by addressing a variety of factors such as information, psychosocial support, clinician education, and standardised guidelines. 

  • 158.
    Krantz, David
    et al.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Hartana, Ciputra Adijaya
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Winerdal, Malin E.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Johansson, Markus
    Sundsvall Hosp, Dept Urol, Sundsvall, Sweden;Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Dept Urol, Vasteras, Sweden.
    Jakubczyk, Tomasz
    Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden.
    Huge, Ylva
    Linkoping Univ, Dept Clin & Expt Med, Div Urol, Linkoping, Sweden.
    Aljabery, Firas
    Linkoping Univ, Dept Clin & Expt Med, Div Urol, Linkoping, Sweden.
    Palmqvist, Karin
    Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden;Ostersund Cty Hosp, Dept Surg, Urol Sect, Ostersund, Sweden.
    Zirakzadeh, A. Ali
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden;Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.
    Holmstrom, Benny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Riklund, Katrine
    Umea Univ, Dept Radiat Sci, Diagnost Radiol, Umea, Sweden.
    Sherif, Amir
    Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden;Linkoping Univ, Dept Clin & Expt Med, Div Urol, Linkoping, Sweden.
    Winqvist, Ola
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 688-692Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Evidence indicates that neoadjuvant chemotherapy (NAC) may promote antitumour immune responses by activating T cells. The tumour-draining sentinel node (SN) is a key site to study tumour-specific T cell activation, being the primary immunological barrier against the tumour. In this prospective study, we set out to elucidate the effects of NAC on T cell subsets in the SNs of patients with muscle-invasive urothelial bladder cancer. We found that CD8(+) effector T (Teff) cell exhaustion was reduced after NAC treatment, while cytotoxicity was increased. Additionally, in complete responders (CR patients), these cells were functionally committed effectors, as displayed by epigenetic analysis. In CD4(+) Teffs, NAC treatment was associated with increased clonal expansion of tumour-specific SN-derived cells, as demonstrated by a specific cell reactivity assay. In contrast, we observed an attenuating effect of NAC on regulatory T cells (Tregs) with a dose-dependent decrease in Treg frequency and reduced effector molecule expression in the remaining Tregs. In addition, multicolour flow cytometry analysis revealed that CR patients had higher Teff to activated Treg ratio, promoting antitumoural T cell activation. These results suggest that NAC reinforces the antitumour immune response by activating the effector arm of the T cell compartment and diminishing the influence of suppressive Tregs. Patient summary: In this report, we analysed the effect of chemotherapy on immune cell subsets of 40 patients with advanced bladder cancer. We found that chemotherapy has a positive effect on immune effector T cells, whereas an opposite, diminishing effect was observed for immune-suppressive regulatory T cells. We conclude that chemotherapy reinforces the antitumour immune response in bladder cancer patients.

  • 159. Kristiansen, Anna
    et al.
    Drevin, Linda
    Uppsala University Hospital.
    Delahunt, Brett
    Samaratunga, Hemamali
    Robinson, David
    Franck Lissbrant, Ingela
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci PS Urol & Androl, Umeå, Sweden.
    Egevad, Lars
    Prognostic significance and biopsy characteristics of prostate cancer with seminal vesicle invasion on radical prostatectomy: a nationwide population-based study.2017Ingår i: Pathology (Sydney), ISSN 0031-3025, E-ISSN 1465-3931, Vol. 49, nr 7, s. 715-720, artikel-id S0031-3025(17)30323-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The objective of this study was to evaluate the prognostic significance of seminal vesicle invasion (SVI, pT3b) compared with extraprostatic extension (EPE) alone (pT3a) after radical prostatectomy, and to correlate pre-operative biopsy pathology with SVI and EPE. The National Prostate Cancer Register includes all prostate cancers diagnosed in Sweden. We analysed 4063 cases with stage category pT3a and 1371 cases with pT3b at radical prostatectomy between 2000 and 2012. Associations between pT3a and pT3b and progression were evaluated and adjusted for year, age, biopsy grade and s-PSA. Needle biopsy findings in these stages were compared. Patients with pT3b (n=1371) had a higher risk of death from prostate cancer (HR 2.3, 95% CI 1.5-3.3, p<0.001) and death from any cause (HR 1.5, 95% CI 1.2-1.8, p<0.001) than those with pT3a (n=4063). They were also more likely to be treated with post-operative radiotherapy (HR 1.5, 95% CI 1.4-1.7, p<0.001) or androgen deprivation therapy (HR 3.0, 95% CI 2.5-3.7, p<0.001), indicating clinical progression. Yet, disease-specific survival of patients with stage pT3b was 94% after 6 years. Median cancer extent in pre-operative biopsies of pT3a and pT3b was 14 and 24 mm (p<0.001), number of positive cores was four and five, (p<0.001) and biopsy Gleason score was 8-10 in 11.6% and 27.3%, respectively (p<0.001). SVI of prostate cancer is associated with worse outcome after radical prostatectomy than EPE alone. However, few patients with SVI die within 6 years from surgery, suggesting that radical prostatectomy may be curative in locally advanced cancers.

  • 160.
    Ladjevardi, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Imaging and Treatment Outcome of Potentially Curable Prostate Cancer2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The over-all aim of the present study was to compare the results of treatment with curative intent, with conservative treatment in men with prostate cancer (PCa) without distant metastases.

    In a population-based cohort in Sweden, the predictive value of prostate-specific antigen (PSA) was evaluated and the relative survival of men considered plausible candidates for treatment with curative intent was investigated.

    We also evaluated the association between curative treatment and cause-specific mortality, and over-all as well as relative survival in men diagnosed with PCa with a serum PSA level between 20 and 100 ng/ml.

    Due to the uncertainly of transrectal ultrasound-guided biopsy in the diagnosis of PCa, we created a model for prostate imaging  to increase the safety of guided Core Needle Biopsy (CNB) in men with suspect PCa, thereby improving staging. 

    Material and methods. The cohorts in the first three studies were prospectively included in a population-based register (the National Prostate Cancer Register). Study IV was a clinical study on patients included between 2010 and 2011.

    Results. Regardless of Gleason Score, a positive relationship between survival and serum PSA level categories in patients with a PSA level> 4 ng/ml was found, but a paradoxical inverse relationship was observed in men with a PSA level < 4 ng/ml. Men with a well-differentiated tumour had a 5-year relative survival exceeding 100% regardless of treatment. The survival rate for moderately and poorly differentiated tumours was poor for men managed conservatively. The 10-year cause-specific mortality for patients with PSA 20-50 ng/ml was 36% for patients treated without and 13% for patients treated with curative intent. For patients with a PSA 50-100 ng/ml the 10-year cause-specific mortality was 55% for conservative and 20% for patients treated with curative intent.

    PCa detection by CNB, magnetic resonance imaging (MR) with ADC (Apparent diffusion coefficient), magnetic resonance spectroscopic imaging (MRSI) and Positron Emission Tomography (PET/CT) ¹¹C Acetate imaging applied to 10 sections of the prostate demonstrated clear conformity between MRI ADC mapping and postoperative findings, showing high specificity (87%) and sensitivity (95%).

    Conclusion. The inverse relationship between relative survival and PSA at levels below 4 ng/ml should be considered when choosing a PSA cut-off level. Outcome differs little between conservative management and treatment with curative intent in men with localised well- to moderately differentiated tumours over a 10-yr period. For men with poorly differentiated tumours, on the other hand, choice of treatment is crucial for outcome. Treatment with curative intent is beneficial in the group of men with prostate cancer and PSA levels between 20 and 100 ng/ml without distant metastases. A combination of MRI , diffusion ADC and MRSI may provide an improved model for imaging of the prostate for targeted biopsy.

    Delarbeten
    1. The impact of prostate-specific antigen level at diagnosis on the relative survival of 28,531 men with localized carcinoma of the prostate
    Öppna denna publikation i ny flik eller fönster >>The impact of prostate-specific antigen level at diagnosis on the relative survival of 28,531 men with localized carcinoma of the prostate
    2008 (Engelska)Ingår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 112, nr 4, s. 813-9Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: To evaluate the predictive value of prostate-specific antigen (PSA) in a population-based cohort, the authors analyzed relative survival in all men with localized prostate cancer who were registered in the Swedish National Prostate Cancer Register (NPCR) from 1996 to 2005. METHODS: All men aged <75 years with localized tumors were identified in the NPCR. A Poisson regression analysis was performed using observed death as response and the expected death rate as offset. The expected and observed numbers of survivors were calculated with stratification for PSA level and 3 categories of tumor differentiation (Gleason score 2-6, 7, and 8-10). The regression model included PSA as linear splines with a breakpoint at a PSA level of 4 ng/mL and with tumor differentiation as a categoric variable. RESULTS: The Poisson regression analysis indicated a U-shaped curve for all 3 groups, with a negative correlation between PSA and relative survival in men with PSA levels <4 ng/mL and a positive correlation for men with PSA levels >4 ng/mL. The correlation was significant for all 3 groups, but the negative correlation between PSA and relative survival was significantly more pronounced in the group with Gleason scores from 8 to 10 than in the other 2 Gleason score groups. CONCLUSIONS: The demonstration of an inverse correlation between PSA level and relative survival in the group of men with PSA levels <4 ng/mL indicated the presence of a small but clinically important subgroup with undifferentiated tumors who have cells that have lost the ability to secrete PSA. This group should be taken into consideration when deciding on treatment and when choosing a cutoff level in PSA screening programs.

    Nyckelord
    prostate cancer, prostate-specific antigen, relative survival, prognosis, Gleason score, population-based
    Nationell ämneskategori
    Urologi och njurmedicin
    Identifikatorer
    urn:nbn:se:uu:diva-88072 (URN)10.1002/cncr.23235 (DOI)000253023700010 ()18098207 (PubMedID)
    Tillgänglig från: 2009-01-20 Skapad: 2009-01-20 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    2. Tumour Grade, Treatment, and Relative Survival in a Population-based Cohort of Men with Potentially Curable Prostate Cancer
    Öppna denna publikation i ny flik eller fönster >>Tumour Grade, Treatment, and Relative Survival in a Population-based Cohort of Men with Potentially Curable Prostate Cancer
    2010 (Engelska)Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, nr 4, s. 631-638Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: There is insufficient information regarding the benefit of treatment with curative intent for men with localised poorly differentiated prostate cancer (PCa). Objective: To evaluate relative survival in men with potentially curable PCa in relation to Gleason score (GS) and treatment as practiced in the community at large. Design, setting, and participants: A population-based study including all men with localised PCa registered in Sweden's National Prostate Cancer Register. Interventions: Hormonal therapy, watchful waiting, and treatment with curative intent. Measurements: The ratio of observed deaths to expected deaths, determined from survival in the general male population of the same age, was assessed using Poisson regression analysis, with GS and treatment as covariates. Interaction between GS and treatment was tested in a multivariate Cox proportional hazard analysis. Results and limitations: A total of 31 903 men with potentially curable tumour (T1-T3, N0/NX, M0/MX, age < 75 yr, and prostate-specific antigen [PSA] < 20 ng/ml) were identified. GS was recorded for 28 454 of these men. Some 19 606 men (60.8%) were treated with curative intent, and 12 645 men (39.2%) were given either hormonal treatment or expectant management. The ratios between observed and expected survival gradually increased for men with GS 10, with GS to 3.3 for men treated conservatively and to 1.4 for men treated with curative intent. There was a significant interaction between GS and treatment, with a relatively greater benefit from treatment with curative intent for men with high-grade tumours. The results have to be interpreted with some caution, as there was no randomisation between the treatment groups. Conclusions: Survival for men with well-differentiated tumours is close to that of the general population, regardless of treatment, but the outcome is dismal for men with poorly differentiated tumours, whichever treatment is applied. Nevertheless, men with poorly differentiated tumours benefit more from curative treatment than do men with well-differentiated tumours.

    Nyckelord
    Epidemiology, Conservative management, Curative management, Prostate cancer, Radical prostatectomy, Radiotherapy
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-136812 (URN)10.1016/j.eururo.2009.03.007 (DOI)000275739300020 ()
    Tillgänglig från: 2010-12-14 Skapad: 2010-12-14 Senast uppdaterad: 2017-12-11Bibliografiskt granskad
    3. Treatment with curative intent and survival in men with high-risk prostate cancer: A population-based study of 11 380 men with serum PSA level 20–100 ng/mL
    Öppna denna publikation i ny flik eller fönster >>Treatment with curative intent and survival in men with high-risk prostate cancer: A population-based study of 11 380 men with serum PSA level 20–100 ng/mL
    Visa övriga...
    2013 (Engelska)Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 111, nr 3, s. 381-388Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Study Type - Prognosis inception (cohort)

    Level of Evidence 2

    What's known on the subject? and What does the study add?

    There are two randomized controlled trials showing that radiotherapy can be beneficial for men with locally advanced prostate cancer. The present study confirms the importance of curative treatment for men with high-risk prostate cancer.

    OBJECTIVE:

    •  To investigate the influence of curative treatment on cause-specific mortality in men diagnosed with prostate cancer (PCa) with serum prostate-specific antigen (PSA) levels between 20 and 100 ng/mL.

    MATERIALS AND METHODS:

    •  Patients with PCa (T1-4, N0/N1/NX, M0/MX), PSA 20-100 ng/mL and age ≤75 years were identified in the National Prostate Cancer Register of Sweden.

    •  Data on co-morbidity diagnoses were obtained from the National Patient Register and cause of death from the Cause of Death Register.

    •  Following adjustment for age at diagnosis, co-morbidity burden, Gleason score, T-category, PSA level and cause-specific mortality in relation to treatment were estimated using Cox regression analysis.

    RESULT:

    •  A total of 11 380 men were diagnosed with PCa between 1996 and 2008 and fulfilled the inclusion criteria.

    •  The cumulative 10-year PCa-specific mortality was 36% for patients receiving only palliative treatment and 13% for those treated with curative intent.

    •  For the 8462 (74%) patients with PSA levels from 20 to 50 ng/mL at diagnosis, the hazard ratio for death from PCa was 0.23 (95% confidence interval 0.19-0.27) for those treated with curative intent compared with those given palliative treatment after adjusting for age, co-morbidity, T category, PSA level and Gleason score. The corresponding hazard ratio was 0.22 (95% confidence interval 0.17-0.30) for patients with PSA levels from 51 to 100 ng/mL.

    CONCLUSION:

    •  Treatment with curative intent for men with high-risk PCa was associated with reduced cause-specific mortality and should be considered even when serum PSA exceeds 20 ng/mL.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-190088 (URN)10.1111/j.1464-410X.2012.11320.x (DOI)000315395200022 ()22758210 (PubMedID)
    Tillgänglig från: 2013-01-07 Skapad: 2013-01-07 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    4. Imaging of the prostate indicating area for targeted biopsy
    Öppna denna publikation i ny flik eller fönster >>Imaging of the prostate indicating area for targeted biopsy
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Urologi och njurmedicin Radiologi och bildbehandling
    Identifikatorer
    urn:nbn:se:uu:diva-171753 (URN)
    Tillgänglig från: 2012-03-27 Skapad: 2012-03-27 Senast uppdaterad: 2012-05-21
  • 161.
    Ladjevardi, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Imaging of the prostate indicating area for targeted biopsyManuskript (preprint) (Övrigt vetenskapligt)
  • 162.
    Ladjevardi, Sam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Auer, Gert
    Castro, Juan
    Ericsson, Christer
    Zetterberg, Anders
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Wiksell, Hans
    Jorulf, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Prostate biopsy sampling causes hematogenous dissemination of epithelial cellular material2014Ingår i: Disease Markers, ISSN 0278-0240, E-ISSN 1875-8630, s. 707529-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The extent of epithelial cellular material (ECM) occurring in venous blood samples after diagnostic core needle biopsy (CNB) was studied in 23 patients with CNB diagnosed prostate cancer without provable metastases and 15 patients without cancer. The data show a significant increase of ECM in the peripheral blood sampled 20 seconds or 30 minutes after the last of 10 CNB procedures compared to the number of ECM detectable in the blood samples taken before the performance of CNB. The data indicate that diagnostic CNB of prostate cancer causes an extensive tissue trauma with a potential risk of cancer cell dissemination.

  • 163.
    Ladjevardi, Sam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Berglund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Varenhorst, Eberhard
    Bratt, Ola
    Widmark, Anders
    Sandblom, Gabriel
    Treatment with curative intent and survival in men with high-risk prostate cancer: A population-based study of 11 380 men with serum PSA level 20–100 ng/mL2013Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 111, nr 3, s. 381-388Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Study Type - Prognosis inception (cohort)

    Level of Evidence 2

    What's known on the subject? and What does the study add?

    There are two randomized controlled trials showing that radiotherapy can be beneficial for men with locally advanced prostate cancer. The present study confirms the importance of curative treatment for men with high-risk prostate cancer.

    OBJECTIVE:

    •  To investigate the influence of curative treatment on cause-specific mortality in men diagnosed with prostate cancer (PCa) with serum prostate-specific antigen (PSA) levels between 20 and 100 ng/mL.

    MATERIALS AND METHODS:

    •  Patients with PCa (T1-4, N0/N1/NX, M0/MX), PSA 20-100 ng/mL and age ≤75 years were identified in the National Prostate Cancer Register of Sweden.

    •  Data on co-morbidity diagnoses were obtained from the National Patient Register and cause of death from the Cause of Death Register.

    •  Following adjustment for age at diagnosis, co-morbidity burden, Gleason score, T-category, PSA level and cause-specific mortality in relation to treatment were estimated using Cox regression analysis.

    RESULT:

    •  A total of 11 380 men were diagnosed with PCa between 1996 and 2008 and fulfilled the inclusion criteria.

    •  The cumulative 10-year PCa-specific mortality was 36% for patients receiving only palliative treatment and 13% for those treated with curative intent.

    •  For the 8462 (74%) patients with PSA levels from 20 to 50 ng/mL at diagnosis, the hazard ratio for death from PCa was 0.23 (95% confidence interval 0.19-0.27) for those treated with curative intent compared with those given palliative treatment after adjusting for age, co-morbidity, T category, PSA level and Gleason score. The corresponding hazard ratio was 0.22 (95% confidence interval 0.17-0.30) for patients with PSA levels from 51 to 100 ng/mL.

    CONCLUSION:

    •  Treatment with curative intent for men with high-risk PCa was associated with reduced cause-specific mortality and should be considered even when serum PSA exceeds 20 ng/mL.

  • 164.
    Ladjevardi, Sam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Sandblom, Gabriel
    Berglund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Varenhorst, Eberhard
    Tumour Grade, Treatment, and Relative Survival in a Population-based Cohort of Men with Potentially Curable Prostate Cancer2010Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, nr 4, s. 631-638Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is insufficient information regarding the benefit of treatment with curative intent for men with localised poorly differentiated prostate cancer (PCa). Objective: To evaluate relative survival in men with potentially curable PCa in relation to Gleason score (GS) and treatment as practiced in the community at large. Design, setting, and participants: A population-based study including all men with localised PCa registered in Sweden's National Prostate Cancer Register. Interventions: Hormonal therapy, watchful waiting, and treatment with curative intent. Measurements: The ratio of observed deaths to expected deaths, determined from survival in the general male population of the same age, was assessed using Poisson regression analysis, with GS and treatment as covariates. Interaction between GS and treatment was tested in a multivariate Cox proportional hazard analysis. Results and limitations: A total of 31 903 men with potentially curable tumour (T1-T3, N0/NX, M0/MX, age < 75 yr, and prostate-specific antigen [PSA] < 20 ng/ml) were identified. GS was recorded for 28 454 of these men. Some 19 606 men (60.8%) were treated with curative intent, and 12 645 men (39.2%) were given either hormonal treatment or expectant management. The ratios between observed and expected survival gradually increased for men with GS 10, with GS to 3.3 for men treated conservatively and to 1.4 for men treated with curative intent. There was a significant interaction between GS and treatment, with a relatively greater benefit from treatment with curative intent for men with high-grade tumours. The results have to be interpreted with some caution, as there was no randomisation between the treatment groups. Conclusions: Survival for men with well-differentiated tumours is close to that of the general population, regardless of treatment, but the outcome is dismal for men with poorly differentiated tumours, whichever treatment is applied. Nevertheless, men with poorly differentiated tumours benefit more from curative treatment than do men with well-differentiated tumours.

  • 165.
    Ladjevardi, Sam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Juhlin, C
    Wärnberg, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    [A case report. FDG-PET in occult breast cancer]2002Ingår i: Lakartidningen, Vol. 99, s. 524-Artikel i tidskrift (Övrigt vetenskapligt)
  • 166.
    Ladjevardi, Sam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Juhlin, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wärnberg, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    FDG-PET vic ockult bröstcancer2002Ingår i: Läkartidningen, Vol. 99, s. 524-Artikel i tidskrift (Övrigt vetenskapligt)
  • 167.
    Ladjevardi, Sam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Weis, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Tolf, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Molekylär och morfologisk patologi.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    von Below, Catrin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Jorulf, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    A Comparison of Different Imaging Techniques for Localisation of Cancers in the Prostate2014Ingår i: Open Prostate Cancer Journal, ISSN 1876-8229, Vol. 7, s. 1-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The diagnostic accuracy of standard transrectal ultrasound-guided (TRUL) biopsy is limited due to the finite number of cores that can be obtained. It has been shown that the technique is not sufficiently reliable in defining the location and extent of prostatic cancer. The main aim of this study was to investigate the effectiveness of magnetic resonance imaging (MRI), and positron emission tomography (PET/CT) imaging techniques in pinpointing potential tumour lesions prior to prostate biopsy.

    Material and methods

    The study cohort consisted of 45 men with a raised prostate specific-antigen (PSA) level and/or suspected prostate cancer (PCa) at digital rectal examinations (DRE). Of the 45 patients, 23 had PCa detected with core needle biopsy (CNB). All had 11C acetate PET/CT imaging. Ten of those 23 patients underwent radical prostatectomy (RP), of those ten patients, eight patients had MR spectroscopic imaging (MRSI) with 3 T and six had diffusion weighted imaging (DWI) with apparent diffusion coefficient calculation (MRI DWI ADC). CNB, PET/CT, 2D MRSI and ADC map results were compared with postoperative specimen histopathology.

    Results

    The sensitivity of CNB, PET/CT, MRSI and DWI ADC were 0.53, 0.55, 0.79 and 0.95, whereas the specificity of was 0.88, 0.87, 0.46 and 0.73, respectively.

    Conclusion

    MRI improves the PCa detection by defining the areas of interest for targeted CNB of the prostate and can reduce the number of biopsies required

  • 168.
    Laurell, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Lönnemark, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Brekkan, Einar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Magnusson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Tolf, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Wallgren, Anna Carin
    Karolinska Inst, Dept Pathol, Stockholm, Sweden.
    Andersson, Bengt
    Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg, Sweden.
    Adamson, Lars
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Kiessling, Rolf
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Karlsson-Parra, Alex
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Immunicum AB, Gothenburg, Sweden.
    Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma.2017Ingår i: Journal for immunotherapy of cancer, ISSN 2051-1426, Vol. 5, artikel-id 52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn't require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off- the-shelf immune enhancer. The use of MHC-incompatible allogeneic DCs will further induce a local rejection process at the injection site that is expected to further enhance recruitment and maturation of endogenous bystander DCs.

    METHODS: Twelve intermediate and poor risk patients with newly diagnosed metastatic renal cell carcinoma (mRCC) where included in a phase I/II study. Pro-inflammatory allogeneic DCs were produced from a leukapheresis product collected from one healthy blood donor and subsequently deep-frozen. A dose of 5-20 × 10(6) DCs (INTUVAX) was injected into the renal tumor twice with 2 weeks interval before planned nephrectomy and subsequent standard of care.

    RESULTS: No INTUVAX-related severe adverse events were observed. A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney tumors. No objective tumor response was observed and 6 out of 11 evaluable patients have subsequently received additional treatment with standard tyrosine kinase inhibitors (TKI). Three of these 6 patients experienced an objective tumor response including one sunitinib-treated patient who responded with a complete and durable regression of 4 brain metastases. Median overall survival (mOS) is still not reached (currently 42.5 months) but has already passed historical mOS in patients with unfavourable risk mRCC on standard TKI therapy.

    CONCLUSIONS: Our findings indicate that intratumoral administration of proinflammatory allogeneic DCs induces an anti-tumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated.

    TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01525017.

  • 169. Lauritzen, Märta
    et al.
    Greis, Gunvor
    Sandberg, Agneta
    Wedren, Hans
    Ojdeby, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Henningsohn, Lars
    Intermittent self-dilatation after internal urethrotomy for primary urethral strictures: a case-control study2009Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, nr 3, s. 220-5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To retrospectively evaluate the effects of intermittent self-dilatation (ISD) on the natural course of urethral strictures after an internal urethrotomy. MATERIAL AND METHODS: A retrospective case-control analysis of all males who had undergone a first time internal urethrotomy due to a urethral stricture in 1998-2000 at 15 urological departments in Sweden. Out of 217 included patients 162 were treated with internal urethrotomy only and 55 with internal urethrotomy followed by postoperative ISD. Demographic data including stricture localization, stricture aetiology and reoperation dates, as well as postoperative indwelling catheter and antibiotic treatment, were collected from the medical records. Factors concerning the ISD were also gathered: postoperative starting time, dilatation catheter size, dilatation frequency and time for retreatment. All patients' medical records were followed for 3-6 years until 2003. RESULTS: The median time until recurrence (surgical reoperation) was 732 days in the ISD group and 167 days in the non-ISD group (p<0.0001). The frequency of recurrence after internal urethrotomy was 9% (5/55) in the ISD group and 31% in the non-ISD group (51/162) during the observational follow-up period (p=0.0007). There was a higher risk of recurrence among those with a traumatic aetiology (39/104) compared with those with unknown aetiology (14/89) (p=0.0005). Patients with a postoperative catheter had a lower risk of recurrence (40/172) than those without one (16/45) (p=0.01). CONCLUSIONS: Postoperative ISD of a urethral stricture, primarily treated by internal urethrotomy, significantly reduces the stricture recurrence rate as well as delaying the time until recurrence.

  • 170. Letocha, H
    et al.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Westlin, J E
    Fasth, K J
    Nilsson, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Positron emission tomography with L-methyl-11C-methionine in the monitoring of therapy response in muscle-invasive transitional cell carcinoma of the urinary bladder1994Ingår i: British Journal of Urology, ISSN 0007-1331, E-ISSN 1365-2176, Vol. 74, nr 6, s. 767-774Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    To investigate whether positron emission tomography (PET) with L-methyl-11C-methionine as a tracer could be used for diagnostic purposes and for evaluation of therapy in patients with varying stages of urinary bladder cancer treated with chemotherapy.

    PATIENTS AND METHODS:

    PET was employed in 44 separate examinations involving 29 patients (24 men and five women with a median age of 68 years [mean 66, range 47-78]) with localized or metastatic transitional cell carcinoma of the urinary bladder. In four patients PET examinations were performed prior to the commencement of chemotherapy, and after one course and after three courses.

    RESULTS:

    The diagnostic accuracy of PET was poor. The technique did not monitor the therapeutic effect of neoadjuvant chemotherapy, producing results that correlated with therapy outcome. PET identified those patients who responded less successfully to therapy.

    CONCLUSION:

    PET with L-methyl-11C-methionine demonstrates alterations in tumour metabolism long before visible changes appear on computed tomography or magnetic resonance imaging. Further work is required to develop more specific tracers.

  • 171.
    Li, Weiqiang
    et al.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Middha, Mridu
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Bicak, Mesude
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Sjoberg, Daniel D.
    Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
    Vertosick, Emily
    Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
    Dahlin, Anders
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Häggström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umeå Univ, Dept Biobank Res, Umeå, Sweden.
    Hallmans, Goran
    Umea Univ, Dept Publ Hlth & Clin Med, Nutr Res, Umea, Sweden.
    Ronn, Ann-Charlotte
    Karolinska Univ Hosp, Clin Res Ctr, Huddinge, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Ulmert, David
    Sloan Kettering Inst, Mol Pharmacol Program, New York, NY USA.
    Lilja, Hans
    Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY 10065 USA;Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA;Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA;Univ Oxford, Nuffield Dept Surg Sci, Oxford, England;Lund Univ, Dept Translat Med, Malmo, Sweden.
    Klein, Robert J.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Genome-wide Scan Identifies Role for AOX1 in Prostate Cancer Survival2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 710-719Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Most men diagnosed with prostate cancer have low-risk cancers. How to predict prostate cancer progression at the time of diagnosis remains challenging. Objective: To identify single nucleotide polymorphisms (SNPs) associated with death from prostate cancer. Design, setting, and participants: Blood samples from 11 506 men in Sweden were collected during 1991-1996. Of these, 1053 men were diagnosed with prostate cancer and 245 died from the disease. Stage and grade at diagnosis and outcome information were obtained, and DNA from all cases was genotyped. Outcome measurements and statistical analysis: A total of 6 126 633 SNPs were tested for association with prostate-cancer-specific survival time using a Cox proportional hazard model, adjusted for age, stage, and grade at diagnosis. A value of 1 x 10(-6) was used as suggestive significance threshold. Positive candidate SNPs were tested for association with gene expression using expression quantitative trait locus analysis. Results and limitations: We found 12 SNPs at seven independent loci associated with prostate-cancerspecific survival time. One of 6 126 633 SNPs tested reached genome-wide significance (p < 5 x 10(-8)) and replicated in an independent cohort: rs73055188 (p = 5.27 x 10(-9), per-allele hazard ratio [HR] = 2.27, 95% confidence interval [CI] 1.72-2.98) in the AOX1 gene. A second SNP reached a suggestive level of significance (p <1 x 10(-6)) and replicated in an independent cohort: rs2702185 (p = 7.1 x 10(-7), per-allele HR = 2.55, 95% CI = 1.76-3.69) in the SMG7 gene. The SNP rs73055188 is correlated with AOX1 expression levels, which is associated with biochemical recurrence of prostate cancer in independent cohorts. This association is yet to be validated in other ethnic groups. Conclusions: The SNP rs73055188 at the AOX1 locus is associated with prostate-cancer-specific survival time, and AOX1 gene expression level is correlated with biochemical recurrence of prostate cancer. Patient summary: We identify two genetic markers that are associated with prostate-cancer-specific survival time.

  • 172.
    Licciardello, Marco P.
    et al.
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Inst Canc Res, Canc Res UK Canc Therapeut Unit, London, England..
    Ringler, Anna
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Markt, Patrick
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Univ Innsbruck Hosp, Dept Pharm, Innsbruck, Austria..
    Klepsch, Freya
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Chem Comp Grp Inc, Cologne, Germany..
    Lardeau, Charles-Hugues
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Austrian Acad Sci, CeMM Res Ctr Mol Med, Christian Doppler Lab Chem Epigenet & Anti Infect, Vienna, Austria..
    Sdelci, Sara
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Schirghuber, Erika
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Austrian Acad Sci, CeMM Res Ctr Mol Med, Christian Doppler Lab Chem Epigenet & Anti Infect, Vienna, Austria..
    Mueller, Andre C.
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Caldera, Michael
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Wagner, Anja
    Med Univ Vienna, Dept Pediat & Adolescent Med, Christian Doppler Lab Mol Stress Res Peritoneal D, Vienna, Austria..
    Herzog, Rebecca
    Med Univ Vienna, Dept Pediat & Adolescent Med, Christian Doppler Lab Mol Stress Res Peritoneal D, Vienna, Austria..
    Penz, Thomas
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Schuster, Michael
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Boidol, Bernd
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Austrian Acad Sci, CeMM Res Ctr Mol Med, Christian Doppler Lab Chem Epigenet & Anti Infect, Vienna, Austria..
    Duernberger, Gerhard
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Gregor Mendel Inst, Vienna, Austria..
    Folkvaljon, Yasin
    Umea Univ Hosp, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ Hosp, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.
    Ivanov, Vladimir
    Enamine Ltd, Kiev, Ukraine..
    Colinge, Jacques
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Univ Montpellier, Fac Med, Montpellier, France.;Inst Reg Canc Montpellier, INSERM U1194, Inst Rech Cancerol Montpellier, Montpellier, France..
    Bock, Christoph
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Med Univ Vienna, Dept Lab Med, Vienna, Austria.;Max Planck Inst Informat, Saarland Informat Campus, Saarbrucken, Germany..
    Kratochwill, Klaus
    Med Univ Vienna, Dept Pediat & Adolescent Med, Christian Doppler Lab Mol Stress Res Peritoneal D, Vienna, Austria..
    Menche, Joerg
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Bennett, Keiryn L.
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Kubicek, Stefan
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Austrian Acad Sci, CeMM Res Ctr Mol Med, Christian Doppler Lab Chem Epigenet & Anti Infect, Vienna, Austria..
    A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor2017Ingår i: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 13, nr 7, s. 771-778Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these drugs modulates the stability of the androgen receptor (AR) and resensitizes AR-mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for gamma-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients.

  • 173.
    Liedberg, Fredrik
    et al.
    Skane Univ Hosp, Dept Urol, Jan Waldenstroms Gata 7, SE-20502 Malmo, Sweden;Lund Univ, Inst Translat Med, Jan Waldenstroms Gata 7, SE-20502 Malmo, Sweden.
    Hagberg, Oskar
    Reg Canc Ctr South, Lund, Sweden.
    Aljabery, Firas
    Linkoping Univ, Dept Clin & Expt Med, Div Urol, Linkoping, Sweden.
    Gardmark, Truls
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Dept Urol, Stockholm, Sweden.
    Jahnson, Staffan
    Linkoping Univ, Dept Clin & Expt Med, Div Urol, Linkoping, Sweden.
    Jancke, Georg
    Skane Univ Hosp, Dept Urol, Jan Waldenstroms Gata 7, SE-20502 Malmo, Sweden;Lund Univ, Inst Translat Med, Jan Waldenstroms Gata 7, SE-20502 Malmo, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sch Hlth & Med Sci, Dept Urol, Orebro, Sweden.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Sherif, Amir
    Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Gothenburg, Sweden.
    Häggström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, Umea, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Sch Med, London, England.
    Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study2019Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 124, nr 3, s. 449-456Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    To investigate the association between hospital volume and overall survival (OS), cancer‐specific survival (CSS), and quality of care of patients with bladder cancer who undergo radical cystectomy (RC), defined as the use of extended lymphadenectomy (eLND), continent reconstruction, neoadjuvant chemotherapy (NAC), and treatment delay of <3 months.

    Patients and Methods

    We used the Bladder Cancer Data Base Sweden (BladderBaSe) to study survival and indicators of perioperative quality of care in all 3172 patients who underwent RC for primary invasive bladder cancer stage T1–T3 in Sweden between 1997 and 2014. The period‐specific mean annual hospital volume (PSMAV) during the 3 years preceding surgery was applied as an exposure and analysed using univariate and multivariate mixed models, adjusting for tumour and nodal stage, age, gender, comorbidity, educational level, and NAC. PSMAV was either categorised in tertiles, dichotomised (at ≥25 RCs annually), or used as a continuous variable for every increase of 10 RCs annually.

    Results

    PSMAV in the highest tertile (≥25 RCs annually) was associated with improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.75–1.0), whereas the corresponding HR for CSS was 0.87 (95% CI 0.73–1.04). With PSMAV as a continuous variable, OS was improved for every increase of 10 RCs annually (HR 0.95, 95% CI 0.90–0.99). Moreover, higher PSMAV was associated with increased use of eLND, continent reconstruction and NAC, but also more frequently with a treatment delay of >3 months after diagnosis.

    Conclusions

    The current study supports centralisation of RC for bladder cancer, but also underpins the need for monitoring treatment delays associated with referral.

  • 174. Liedberg, Fredrik
    et al.
    Hagberg, Oskar
    Holmang, Sten
    Aliabad, Abolfazl Hosseini
    Jancke, Georg
    Ljungberg, Borje
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Aberg, Hanna
    Jahnson, Staffan
    Local recurrence and progression of non-muscle-invasive bladder cancer in Sweden: a population-based follow-up study2015Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, nr 4, s. 290-295Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. The aim of this study was to investigate recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) in a large population-based setting. Materials and methods. Patients with bladder cancer (stage Ta, T1 or carcinoma in situ) diagnosed in 2004-2007 (n = 5839) in Sweden were investigated 5 years after diagnosis using a questionnaire. Differences in time to recurrence and progression were analysed in relation to age, gender, tumour stage and grade, intravesical treatment, healthcare region, and hospital volume of NMIBC patients (stratified in three equally large groups). Results. Local bladder recurrence and progression occurred in 50 and 9% of the patients, respectively. The rate of local recurrence was 56% in the southern healthcare region compared to 37% in the northern region. A multivariate Cox proportional hazards model, adjusting for age, gender, tumour stage and grade, intravesical treatment, healthcare region and hospital volume, showed that recurrence was associated with TaG2 and T1 disease, no intravesical treatment and treatment in the southern healthcare region, but indicated a lower risk of recurrence in the northern healthcare region. Adjusting for the same factors in a multivariate analysis suggested that increased relative risk of progression correlated with older age, higher tumour stage and grade, and diagnosis in the Uppsala/Orebro healthcare region, whereas such risk was decreased by intravesical treatment (relative risk 0.72, 95% confidence interval 0.55-0.93, p = 0.012). Conclusions. The incidence of NMIBC recurrence and progression was found to be high in Sweden, and important disparities in outcome related to care patterns appear to exist between different healthcare regions.

  • 175. Liedberg, Fredrik
    et al.
    Holmberg, Erik
    Holmäng, Sten
    Ljungberg, Börje
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Månsson, Wiking
    Nunez, Leyla
    Wessman, Catrin
    Wijkström, Hans
    Jahnson, Staffan
    Long-term follow-up after radical cystectomy with emphasis on complications and reoperations: A Swedish population-based survey2012Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, nr 1, s. 14-18Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective.

    To evaluate outcome after radical cystectomy for primary bladder cancer in a large population-based material.

    Material and methods.

    Between 1997 and 2002 all patients treated with radical cystectomy within 3 months after diagnosis of primary bladder cancer without distant metastasis were retrieved through the Swedish Bladder Cancer Registry. A follow-up questionnaire was distributed to all units where the primary registration of patients was performed. Follow-up data on recurrence date were retrieved from the patient charts and causes of death were obtained from the Swedish Cause of Death Registry until 2003.

    Results.

    During the study period radical cystectomy was performed in 39 units in Sweden, of which only five units were considered high-volume hospitals performing 10 or more procedures annually. Mean blood loss was 2300 ml (median 2000 ml) and the 90-day mortality rate was 5.7%. Blood loss was higher in high-volume units than in hospitals with lower hospital volumes, but the 90-day mortality rates were similar. During a median follow-up of 3.5 years, 24% of the patients were submitted to a reoperation. Reoperation rates were significantly higher in patients who received a continent urinary diversion (29%) compared with an ileal conduit (22%, p < 0.015).

    Conclusions.

    Radical cystectomy was associated with a reoperation rate of 24% in Sweden during the study period. The reoperation rates were higher in patients receiving a continent cutaneous diversion or bladder substitution. Blood loss was higher in high-volume units; otherwise, surgical volume did not affect mortality rates, cancer-specific survival or reoperation rates.

  • 176. Liedberg, Fredrik
    et al.
    Holmäng, Sten
    Hosseini, Abolfazl
    Ljungberg, Börje
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Jahnson, Staffan
    Snabba åtgärder vid makrohematuri både angelägna och möjliga: [Fast measures in macro hematuria are both necessary and possible]2012Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 20-21, s. 1034-1035Artikel i tidskrift (Refereegranskat)
  • 177.
    Lindhagen, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Med, Canc Epidemiol Grp, Div Canc Studies,Res Oncol,Guys Hosp, London SE1 9RT, England.;Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden..
    Robinson, David
    Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Kings Coll London, Sch Med, Canc Epidemiol Grp, Div Canc Studies,Res Oncol,Guys Hosp, London SE1 9RT, England.
    How to model temporal changes in comorbidity for cancer patients using prospective cohort data2015Ingår i: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 15, artikel-id 96Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The presence of comorbid conditions is strongly related to survival and also affects treatment choices in cancer patients. This comorbidity is often quantified by the Charlson Comorbidity Index (CCI) using specific weights (1, 2, 3, or 6) for different comorbidities. It has been shown that the CCI increases at different times and with different sizes, so that traditional time to event analysis is not adequate to assess these temporal changes. Here, we present a method to model temporal changes in CCI in cancer patients using data from PCBaSe Sweden, a nation-wide population-based prospective cohort of men diagnosed with prostate cancer. Our proposed model is based on the assumption that a change in comorbidity, as quantified by the CCI, is an irreversible one-way process, i.e., CCI accumulates over time and cannot decrease. Methods: CCI was calculated based on 17 disease categories, which were defined using ICD-codes for discharge diagnoses in the National Patient Register. A state transition model in discrete time steps (i.e., four weeks) was applied to capture all changes in CCI. The transition probabilities were estimated from three modelling steps: 1) Logistic regression model for vital status, 2) Logistic regression model to define any changes in CCI, and 3) Poisson regression model to determine the size of CCI change, with an additional logistic regression model for CCI changes >= 6. The four models combined yielded parameter estimates to calculate changes in CCI with their confidence intervals. Results: These methods were applied to men with low-risk prostate cancer who received active surveillance (AS), radical prostatectomy (RP), or curative radiotherapy (RT) as primary treatment. There were large differences in CCI changes according to treatment. Conclusions: Our method to model temporal changes in CCI efficiently captures changes in comorbidity over time with a small number of regression analyses to perform - which would be impossible with tradition time to event analyses. However, our approach involves a simulation step that is not yet included in standard statistical software packages. In our prostate cancer example we showed that there are large differences in development of comorbidities among men receiving different treatments for prostate cancer.

  • 178. Lindkvist, Björn
    et al.
    Johansen, Dorthe
    Stocks, Tanja
    Concin, Hans
    Bjørge, Tone
    Almquist, Martin
    Häggström, Christel
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden .
    Engeland, Anders
    Hallmans, Göran
    Nagel, Gabriele
    Jonsson, Håkan
    Selmer, Randi
    Ulmer, Hanno
    Tretli, Steinar
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Manjer, Jonas
    Metabolic risk factors for esophageal squamous cell carcinoma and adenocarcinoma: a prospective study of 580,000 subjects within the Me-Can project2014Ingår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, s. 103-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Obesity is associated with an increased risk of esophageal adenocarcinoma (EAC) and a decreased risk of esophageal squamous cell carcinoma (ESCC). However, little is known about the risk of EAC and ESCC related to other metabolic risk factors. We aimed to examine the risk of EAC and ESCC in relation to metabolic risk factors, separately and combined in a prospective cohort study.

    METHODS:

    The Metabolic Syndrome and Cancer cohort includes prospective cohorts in Austria, Norway and Sweden, with blood pressure, lipids, glucose and BMI available from 578 700 individuals. Relative risk (RR) for EAC and ESCC was calculated using Cox's proportional hazards analysis for metabolic risk factors categorized into quintiles and transformed into z-scores. The standardized sum of all z-scores was used as a composite score for the metabolic syndrome (MetS).

    RESULTS:

    In total, 324 histologically verified cases of esophageal cancer were identified (114 EAC, 184 ESCC and 26 with other histology). BMI was associated with an increased risk of EAC (RR 7.34 (95% confidence interval, 2.88-18.7) top versus bottom quintile) and negatively associated with the risk of ESCC (RR 0.38 (0.23-0.62)). The mean value of systolic and diastolic blood pressure (mid blood pressure) was associated with the risk of ESCC (RR 1.77 (1.37-2.29)). The composite MetS score was associated with the risk of EAC (RR 1.56 (1.19-2.05) per one unit increase of z-score) but not ESCC.

    CONCLUSIONS:

    In accordance with previous studies, high BMI was associated with an increased risk of EAC and a decreased risk of ESCC. An association between high blood pressure and risk of ESCC was observed but alcohol consumption is a potential confounding factor that we were not able to adjust for in the analysis. The MetS was associated with EAC but not ESCC. However this association was largely driven by the strong association between BMI and EAC. We hypothesize that this association is more likely to be explained by factors directly related to obesity than the metabolic state of the MetS, considering that no other metabolic factor than BMI was associated with EAC.

  • 179.
    Lindén, Mårten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Proteomic Analysis of Urinary Bladder Cancer: Aiming for Novel Biomarkers2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Urinary bladder cancer is a heterogeneous disease appearing in different forms, e.g. non-muscle invasive and muscle invasive. For all variants, the expression of proteins is interesting to analyze for diagnostic, predictive, prognostic and drug targeting purposes, since it reflects the altered gene expression causing the cancer. Since urothelial cells of the bladder are in direct contact with urine it is likely that this body fluid contains cancer-related proteins. In Paper I, unbiased analysis of proteins in urine from urinary bladder cancer patients and controls, using label-free quantification by mass spectrometry, was applied and four interesting proteins APOE, FGB, LRG and SERPINA1 were selected and further analyzed with western and dot blot. In Paper II, two more proteins, POLR1E and TOP2A, were validated as relevant proteins in bladder cancer urine. In Paper III and IV, the proteins GAL1 and STMN1 were investigated for their prognostic and therapeutic target potential in bladder cancer. In Paper II, III and IV, the expression of seven of the proteins were analyzed on tissue microarrays representing tumour tissue from 360 patients with different tumour stages. For the proteins identified by the urine screening approach, their protein expressions were confirmed in bladder cancer tissue. The expression level in tissue of five of the proteins, APOE, FGB, POLR1E (Paper II), GAL1 (Paper III) and STMN1 (Paper IV), increased with tumour stage, showing diagnostic relevance and three of the proteins, SERPINA1 (Paper II), STMN1 (Paper IV) and GAL1 (Paper III) had prognostic potential in urinary bladder cancer. In addition, GAL1 and STMN1 were demonstrated to be highly expressed in metastatic disease and inhibition of STMN1 reduced cell growth (Paper III and IV), indicating that these proteins are promising drug targets in urinary bladder cancer. In conclusion, the approach of this thesis has generated several candidate protein biomarkers in urine and tissue, validated with independent methods, which have the potential to improve the care for bladder cancer patients.

    Delarbeten
    1. Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer
    Öppna denna publikation i ny flik eller fönster >>Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer
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    2012 (Engelska)Ingår i: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 12, nr 1, s. 135-144Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Nonmuscle invasive tumors of the bladder often recur and thereby bladder cancer patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method, e.g. a urine dipstick test, for monitoring recurrence would thus be advantageous. In this study, the complementary techniques mass spectrometry (MS) and Western blotting (WB)/dot blot (DB) were used to screen the urine samples from bladder cancer patients. High resolving MS was used to analyze and quantify the urinary proteome and 29 proteins had a significantly higher abundance (p<0.05) in bladder cancer samples compared with control urine samples. The increased abundance found in urine from bladder cancer patients compared with controls was confirmed with Western blot for four selected proteins; fibrinogen β chain precursor, apolipoprotein E, α-1-antitrypsin, and leucine-rich α-2-glycoprotein 1. Dot blot analysis of an independent urine sample set pointed out fibrinogen β chain and α-1-antitrypsin as most interesting biomarkers having sensitivity and specificity values in the range of 66-85%. Exploring the Human Protein Atlas (HPA) also revealed that bladder cancer tumors are the likely source of these proteins. They have the potential of being useful in diagnosis, monitoring of recurrence and thus may improve the treatment of bladder tumors, especially nonmuscle invasive tumors.

    Nationell ämneskategori
    Urologi och njurmedicin Cancer och onkologi
    Identifikatorer
    urn:nbn:se:uu:diva-163407 (URN)10.1002/pmic.201000810 (DOI)000298841000016 ()22065568 (PubMedID)
    Tillgänglig från: 2011-12-12 Skapad: 2011-12-12 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
    2. Tumour expression of bladder cancer-associated urinary proteins
    Öppna denna publikation i ny flik eller fönster >>Tumour expression of bladder cancer-associated urinary proteins
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    2013 (Engelska)Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 112, nr 3, s. 407-415Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?:

    • The current basis for diagnosis and prognosis in urinary bladder cancer is based on the pathologists' assessment of a biopsy of the tumour. Urinary biomarkers are preferable as they can be non-invasively sampled. Urinary cytology is the only test with widespread use but is hampered by poor reproducibility and low sensitivity.
    • By studying the protein expression in bladder tumour tissue samples of proteins previously found in elevated levels in the urine of patients with bladder cancer, we have been able to show that these proteins originate from the tumour. The immunoreactivity of three of the investigated proteins increased with higher stage. Also a serine peptidase inhibitor was found to be predictive of progression from non-muscle-invasive to muscle-invasive tumours.

    OBJECTIVES:

    • To analyse the expression of five bladder cancer-associated urinary proteins and investigate if expression is related to the malignant phenotype of the tumour.
    • To explore the possible prognostic value of these proteins.

    PATIENTS AND METHODS:

    • Urine samples, 16 from patients with bladder cancer and 26 from controls, were used in Western Blotting experiments.
    • Tissue microarrays with bladder tissue from 344 patients diagnosed with bladder cancer between 1984 and 2005 was used in immunohistochemistry experiments.
    • The proteins apolipoprotein E (APOE), fibrinogen β chain precursor (FGB), leucine-rich α2-glycoprotein (LRG1), polymerase (RNA) I polypeptide E (POLR1E), α1-antitrypsin (SERPINA1) and topoisomerase 2A (TOP2A) were probed with antibodies validated by the Human Protein Atlas.

    RESULTS:

    • Increased expressions of APOE, FGB and POLR1E were correlated with increased tumour stage (P < 0.001).
    • Expression of SERPINA1 in Ta and T1 tumours was found to increase the risk of tumour progression (hazard ratio 2.57, 95% confidence interval 1.13-5.87; P = 0.025)

    CONCLUSIONS:

    • All proteins previously detected in urine from patients with bladder cancer were also expressed in bladder cancer tissue.
    • The expression of APOE, FGB and POLR1E increased with stage and they are potential diagnostic markers.
    • SERPINA1 was identified as a prognostic marker candidate.
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-197160 (URN)10.1111/j.1464-410X.2012.11653.x (DOI)000321429800024 ()23470167 (PubMedID)
    Anmärkning

    De två sista författarna delar sistaförfattarskapet.

    Tillgänglig från: 2013-03-18 Skapad: 2013-03-18 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    3. Galectin-1, a potential therapeutic target, in primary tumors and metastases of urinary bladder carcinomas
    Öppna denna publikation i ny flik eller fönster >>Galectin-1, a potential therapeutic target, in primary tumors and metastases of urinary bladder carcinomas
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    2013 (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Urinary bladder cancer would gain from new protein biomarkers due to the heterogeneity of disease. The beta-galactoside-binding protein (GAL1) is one such candidate and in present study its prognostic value and expression at protein level in metastatic bladder cancer-disease, have been evaluated. The protein expression of GAL1 was investigated by immunohistochemistry in two tumor cohorts, one with primary tumors of different stage and grade (n=344) and another with primary tumors matched with metastases (n=90). The expression in the actual cancer cells as well as in stroma and blood vessels were considered since the presence of GAL1 in different tissue compartments has shown cancer relevance. The cellular expression increased with increased tumor stage and grade (p<0.001). For the majority of the patients, cells from both primary tumor and metastasis showed a positive immunoreactivity for GAL1 (91% (n=64) for primary tumors with single metastasis (n=70) and 100% (n=20) for primary tumors with multiple metastasis (n=20). Further, strong immunoreactivity in T1 tumor cells correlated with lower risk of recurrence (p<0.05). Both tumors and metastasis exhibited strong stromal-GAL1 staining that could not be correlated with clinical parameters. The expression in vessels showed that T1 tumors surrounded by GAL1 negative blood vessels had a higher risk of progression (p<0.0001) into muscle invasive T2-4 stages. The results show that GAL1 is an important bladder cancer-protein from several aspects. Further, GAL1 is a promising therapeutic target in bladder cancer due to the general expression in advanced disease.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-197192 (URN)
    Tillgänglig från: 2013-03-18 Skapad: 2013-03-18 Senast uppdaterad: 2015-06-24
    4. Stathmin-1 is a promising prognostic factor and potential therapeutic target in urinary bladder cancer
    Öppna denna publikation i ny flik eller fönster >>Stathmin-1 is a promising prognostic factor and potential therapeutic target in urinary bladder cancer
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Aim: The oncoprotein 18/stathmin 1 (STMN1), involved in cell cycle progression and cell migration, has been reported to be expressed in several types of cancer, and is associated with clinical outcome in e.g. breast and liver cancer. The aims in this study were to investigate the clinical significance of STMN1 and to examine if STMN1 might be a possible therapeutic target in urinary bladder cancer.

    Experimental design: Immunohistochemical analyses of STMN1 protein expression were performed in a wide-range tissue microarray (115 Ta-, 115 T1-, 112 T2-4-tumors) and in a metastatic primary tumor/matched metastasis-material (90 patients). In the T24 cell line, the effect of STMN1 on cell proliferation was evaluated by inhibiting the cellular expression of STMN using STMN1-siRNA.

    Results: Patients with T1- or muscle-invasive disease exhibiting high expression of the STMN1 protein had a poorer overall survival (OS) and disease specific survival (DSS). In a multivariate analysis adjusting for stage, age and gender the results were for T2-T4 patients: OS (HR=1.77 95% CI 1.02-3.07; p=0.04) and DSS (HR=2.04 95% CI 1.13-3.68; p=0.02); for T1-4 patients: DSS (HR=1.83 95% CI 1.09-3.08; p=0.02). In the metastatic bladder cancer material, the majority of the patients with one metastasis (69%) and with several matched metastases (70%) were STMN1-positive in both the primary tumor and the matched metastases. Moreover, the ability of the urinary bladder cancer cell line to grow was significantly reduced after 72 hours (p<0.0001) when transfecting the cells with a siRNA targeting STMN1.

    Conclusion: Our results suggest that STMN1 protein-expression has a potential both as a prognostic marker and a novel treatment target in urinary bladder cancer.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Medicinsk vetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-197155 (URN)
    Tillgänglig från: 2013-03-18 Skapad: 2013-03-18 Senast uppdaterad: 2015-06-24
  • 180.
    Lindén, Mårten
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Hemdan, Tammer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Ugge, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Bergström Lind, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    de la Torre, Manuel