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  • 101. Gontero, Paolo
    et al.
    Sylvester, Richard
    Pisano, Francesca
    Joniau, Steven
    Eeckt, Kathy Vander
    Serretta, Vincenzo
    Larre, Stephane
    Di Stasi, Savino
    Van Rhijn, Bas
    Witjes, Alfred J.
    Grotenhuis, Anne J.
    Kiemeney, Lambertus A.
    Colombo, Renzo
    Briganti, Alberto
    Babjuk, Marek
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Oderda, Marco
    Irani, Jacques
    Malats, Nuria
    Baniel, Jack
    Mano, Roy
    Cai, Tommaso
    Cha, Eugene K.
    Ardelt, Peter
    Varkarakis, John
    Bartoletti, Riccardo
    Spahn, Martin
    Johansson, Robert
    Frea, Bruno
    Soukup, Viktor
    Xylinas, Evanguelos
    Dalbagni, Guido
    Karnes, R. Jeffrey
    Shariat, Shahrokh F.
    Palou, Joan
    Prognostic Factors and Risk Groups in T1G3 Non-Muscle-invasive Bladder Cancer Patients Initially Treated with Bacillus Calmette-Guerin: Results of a Retrospective Multicenter Study of 2451 Patients2015Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 67, nr 1, s. 74-82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. Objective: To assess prognostic factors in patients who received bacillus Calmette Guerin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. Design, setting, and participants: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. Outcome measurements and statistical analysis: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). Results and limitations: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age >= 70 yr, size >= 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients >= 70 yr with tumor size >= 3 cm and 13% otherwise. Conclusions: T1G3 patients >= 70 yr with tumors >= 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. Patient summary: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guerin, there is a subgroup of T1G3 patients with age >= 70 yr, tumor size >= 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

  • 102. Gontero, Paolo
    et al.
    Sylvester, Richard
    Pisano, Francesca
    Joniau, Steven
    Oderda, Marco
    Serretta, Vincenzo
    Larré, Stéphane
    Di Stasi, Savino
    Van Rhijn, Bas
    Witjes, Alfred J
    Grotenhuis, Anne J
    Colombo, Renzo
    Briganti, Alberto
    Babjuk, Marek
    Soukup, Viktor
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Irani, Jacques
    Malats, Nuria
    Baniel, Jack
    Mano, Roy
    Cai, Tommaso
    Cha, Eugene K
    Ardelt, Peter
    Vakarakis, John
    Bartoletti, Riccardo
    Dalbagni, Guido
    Shariat, Shahrokh F
    Xylinas, Evanguelos
    Karnes, Robert J
    Palou, Joan
    The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guérin2016Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, nr 1, s. 44-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS).

    PATIENTS AND METHODS: In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette-Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups.

    RESULTS: Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints.

    CONCLUSIONS: Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR.

  • 103. Gonterol, P.
    et al.
    Sylvester, R.
    Pisano, F.
    Joniau, S.
    Eeckt, Kathy Vander
    Serretta, V.
    Larre, S.
    di Stasi, S.
    Van Rhijn, B.
    Witjes, A.
    Grotenhuis, A.
    Colombo, R.
    Brigand, A.
    Babjukl, M.
    Soukupw, V.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Irani, J.
    Malats, N.
    Baniel, J.
    Mano, R.
    Cai, T.
    Cha, E.
    Ardelti, P.
    Vakarakisis, J.
    Bartoletti, R.
    Sphan, M.
    Dalbagnin, G.
    Shariat, S. F.
    Karnes, J.
    Palou, J.
    Prognostic Factors And Risk Groups In T1g3 Patients Initially Treated With Bcg: Results Of A Multicenter Retrospective Series In 1743 Patients2013Ingår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 33, nr 5, s. 2260-2261Artikel i tidskrift (Övrigt vetenskapligt)
  • 104. Gunnarsson, Jonas
    et al.
    Dahlman, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Helenius, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Liss, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lönnemark, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Magnusson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Hematurispåret – en väg att snabbare diagnostisera blåscancer2015Ingår i: Svensk Urologi, nr 3, s. 38-Artikel i tidskrift (Refereegranskat)
  • 105.
    Guðmundsson, Eirikur
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Hellborg, Henrik
    Lundstam, Sven
    Erikson, Stina
    Ljungberg, Börje
    Metastatic Potential in Renal Cell Carcinomas <= 7 cm: Swedish Kidney Cancer Quality Register Data2011Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, nr 5, s. 975-982Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Renal cell carcinoma(RCC) represents 2-3% of all malignancies and accounts for approximately 90% of all kidney malignancies. An increasing proportion of RCCs are discovered incidentally, and the average tumor diameter at diagnosis has decreased over the last few decades. Small RCCs have often been regarded by many as relatively harmless.

    Objective: The objective was to evaluate the incidence of local T-category distribution and lymph node and distant metastases in relation to tumor size in RCCs <= 7 cm in a nationally based patient population.

    Design, setting, and participants: Data were extracted from the National Swedish Kidney Cancer Register containing 3489 RCCs diagnosed between 2005 and 2008. This is a population-based registry including 99% of all RCCs diagnosed nationwide. The study included 2033 patients having a tumor <= 7 cm in diameter.

    Measurements: The size of the tumors was compared with sex, age, cause of diagnosis, Fuhrman grade, RCC type, and TNM category.

    Results and limitations: Most RCCs were discovered incidentally and incidence correlated inversely to tumor size. There were 887 (43%) patients with category T1a tumors, 836 (40%) with category T1b, 174 (8%) with T3a, 131 (6%) with T3b/c, and 12 (1%) patients had invasion of adjacent organs (T4). A total of 309 (15%) patients had lymph node and/or distant metastases. Of the 177 1- to 2-cm RCCs, category T3 tumors were identified in three patients and lymph node and/or distant metastases were identified in 8 (5%). Only for tumors <= 1 cm was there neither advanced stage nor metastasis. The occurrence of locally advanced growth, lymph node and distant metastases, and high tumor grade correlated to tumor size. Patients with Fuhrman grade III or IV had a fourfold greater risk of metastases than grades I or II.

    Conclusions: Lymph node and distant metastases occur even in small RCCs. Risk of metastases increases with tumor size. The data clearly show that small RCCs also have a malignant potential and should be properly evaluated and adequately treated.

  • 106.
    Gårdmark, Truls
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Heinius, Johan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Kan läkarstudenten lära sig urologi på ett länssjukhus?: Rapport från ett IT-baserat utvecklingsprojekt på läkarprogrammet i Uppsala2008Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, nr 32, s. 2171-4Artikel i tidskrift (Refereegranskat)
  • 107. Hagel, Eva
    et al.
    Garmo, Hans
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bratt, Ola
    Johansson, Jan-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Adolfsson, Jan
    Lambe, Mats
    Stattin, Pär
    PCBaSe Sweden: a register-based resource for prostate cancer research2009Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, nr 5, s. 342-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To construct a database for clinical epidemiological prostate cancer research based on linkages between the National Prostate Cancer Register (NPCR) of Sweden, a population-based, nationwide quality database, and other nationwide registries. Material and methods. By use of the individually unique Swedish Personal Identity Number, the NPCR was linked to the Swedish Cancer Registry, the Cause of Death Register, the Prescribed Drug Register, the National Patient Register and the Acute Myocardial Infarction Register, all held at the Centre for Epidemiology at the National Board of Health and Welfare, and the Register of the Total Population, the Longitudinal Integration Database for Health Insurance and Labor Market Studies and the Multi-Generation Register, held at Statistics Sweden, and to the Swedish Hernia Register. Results. Record linkages between the NPCR and the Swedish Cancer Registry, the Cause of Death Register and the Register of the Total Population generated a database, named PCBaSe Sweden, including 80 079 prostate cancer cases, diagnosed between 1 January 1996 and 31 December 2006. Record linkage between PCBaSe Sweden and the Prescribed Drug Register generated 59 721 unique matches and linkage to the Acute Myocardial Infarction Register resulted in 11 459 matches. Conclusion. PCBaSe Sweden is a newly created and unique database with over 80 000 cases of prostate cancer with comprehensive data on inpatient and outpatient care, patterns of use of prescribed drugs and socioeconomic and familial factors. Many topics in clinical prostate cancer epidemiology can be investigated. using PCBaSe Sweden.

  • 108. Halin Bergström, Sofia
    et al.
    Nilsson, Maria
    Adamo, Hanibal
    Thysell, Elin
    Jernberg, Emma
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Widmark, Anders
    Wikström, Pernilla
    Bergh, Anders
    Extratumoral Heme Oxygenase-1 (HO-1) Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth.2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 6, artikel-id e0157280Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1). To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RT-PCR showed that the main site of HO-1 synthesis was HO-1+ macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1+ macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1+ macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1+ macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1+ macrophages may have an important role in prostate cancer.

  • 109. Hammarsten, Peter
    et al.
    Dahl Scherdin, Tove
    Hägglöf, Christina
    Andersson, Pernilla
    Wikström, Pernilla
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Egevad, Lars
    Granfors, Torvald
    Bergh, Anders
    High Caveolin-1 Expression in Tumor Stroma Is Associated with a Favourable Outcome in Prostate Cancer Patients Managed by Watchful Waiting.2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 10, artikel-id e0164016Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the present study we have investigated whether Caveolin-1 expression in non-malignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients managed by watchful waiting. Caveolin-1 was measured in prostate tissues obtained through transurethral resection of the prostate from 395 patients diagnosed with prostate cancer. The majority of the patients (n = 298) were followed by watchful waiting after diagnosis. Tissue microarrays constructed from malignant and non-malignant prostate tissue were stained with an antibody against Caveolin-1. The staining pattern was scored and related to clinicopathologic parameters and outcome. Microdissection and qRT-PCR analysis of Cav-1 was done of the prostate stroma from non-malignant tissue and stroma from Gleason 3 and 4 tumors. Cav-1 RNA expression was highest in non-malignant tissue and decreased during cancer progression. High expression of Caveolin-1 in tumor stroma was associated with significantly longer cancer specific survival in prostate cancer patients. This association remained significant when Gleason score and local tumor stage were combined with Caveolin-1 in a Cox regression model. High stromal Caveolin-1 immunoreactivity in prostate tumors is associated with a favourable prognosis in prostate cancer patients managed by watchful waiting. Caveolin-1 could possibly become a useful prognostic marker for prostate cancer patients that are potential candidates for active surveillance.

  • 110.
    Hammarsten, Peter
    et al.
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Josefsson, Andreas
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden.
    Thysell, Elin
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Lundholm, Marie
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Hagglof, Christina
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Iglesias-Gato, Diego
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Copenhagen, Denmark.
    Flores-Morales, Amilcar
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Copenhagen, Denmark.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Egevad, Lars
    Karolinska Univ Hosp, Dept Pathol & Cytol, Stockholm, Sweden.
    Granfors, Torvald
    Cent Hosp Vasteras, Dept Urol, Vasteras, Sweden.
    Wikstrom, Pernilla
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Bergh, Anders
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Immunoreactivity for prostate specific antigen and Ki67 differentiates subgroups of prostate cancer related to outcome2019Ingår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 32, nr 9, s. 1310-1319Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Based on gene-expression profiles, prostate tumors can be subdivided into subtypes with different aggressiveness and response to treatment. We investigated if similar clinically relevant subgroups can be identified simply by the combination of two immunohistochemistry markers: one for tumor cell differentiation (prostate specific antigen, PSA) and one for proliferation (Ki67). This was analyzed in men with prostate cancer diagnosed at transurethral resection of the prostate 1975-1991 (n = 331) where the majority was managed by watchful waiting. Ki67 and PSA immunoreactivity was related to outcome and to tumor characteristics previously associated with prognosis. Increased Ki67 and decreased PSA were associated with poor outcome, and they provided independent prognostic information from Gleason score. A combinatory score for PSA and Ki67 immunoreactivity was produced using the median PSA and Ki67 levels as cut-off (for Ki67 the upper quartile was also evaluated) for differentiation into subgroups. Patients with PSA low/Ki67 high tumors showed higher Gleason score, more advanced tumor stage, and higher risk of prostate cancer death compared to other patients. Their tumor epithelial cells were often ERG positive and expressed higher levels of ErbB2, phosphorylated epidermal growth factor receptor (pEGF-R) and protein kinase B (pAkt), and their tumor stroma showed a reactive response with type 2 macrophage infiltration, high density of blood vessels and hyaluronic acid, and with reduced levels of caveolin-1, androgen receptors, and mast cells. In contrast, men with PSA high/Ki67 low tumors were characterized by low Gleason score, and the most favorable outcome amongst PSA/Ki67-defined subgroups. Men with PSA low/Ki67 low tumors showed clinical and tumor characteristics intermediate of the two groups above. A combinatory PSA/Ki67 immunoreactivity score identifies subgroups of prostate cancers with different epithelial and stroma phenotypes and highly different outcome but the clinical usefulness of this approach needs to be validated in other cohorts.

  • 111.
    Hartana, C. A.
    et al.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Bergman, E. Ahlen
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Broome, A.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Berglund, S.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Johansson, M.
    Sundsvall Hosp, Dept Urol, Sundsvall, Sweden.
    Alamdari, F.
    Vastmanland Hosp, Dept Urol, Vasteras, Sweden.
    Jakubczyk, T.
    Lanssjukhuset Ryhov, Dept Urol, Jonkoping, Sweden.
    Huge, Y.
    Linkoping Univ, Div Urol, Dept Clin & Expt Med, Linkoping, Sweden.
    Aljabery, F.
    Linkoping Univ, Div Urol, Dept Clin & Expt Med, Linkoping, Sweden.
    Palmqvist, K.
    Ostersund Cty Hosp, Dept Surg, Urol Sect, Ostersund, Sweden.
    Holmström, Benny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Glise, H.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Riklund, K.
    Umea Univ, Dept Radiat Sci, Diagnost Radiol, Umea, Sweden.
    Sherif, A.
    Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
    Winqvist, O.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer2018Ingår i: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 194, nr 1, s. 39-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tissue-resident memory T (T-RM) cells are CD8(+) T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in T-RM cells and correlate it with their functional potential. Fifty-three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in T-RM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in-vitro stimulation were used to evaluate T-RM cell phenotypes. We discovered that tumour T-RM cells have low DNA methylation in the PRF1 locus (32<bold></bold>9% methylation), which corresponds to increased numbers of perforin-expressing T-RM cells. Surprisingly, programmed cell death 1 (PD-1) expression is high in tumour T-RM cells, suggesting exhaustion. Following interleukin-15 and T cell receptor stimulation, perforin and T-bet expressions are enhanced, indicating that T-RM cells from tumours are not terminally exhausted. Moreover, a high number of T-RM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, T-RM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies T-RM cells as potential new targets for cancer immunotherapy.

  • 112.
    Hauffman, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Alfonsson, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård.
    Mattson, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Forslund, Marina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Johansson, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    The development of a Nurse-led Internet-based Learning and Self-care program for cancer patients with symptoms of anxiety and depression: a part of U-CARE2017Ingår i: Cancer Nursing, ISSN 0162-220X, E-ISSN 1538-9804, ISSN 0162-220X, Vol. 40, nr 5, s. E9-E16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Having access to information about the disease and being encouraged to participate in self-care activities may reduce anxiety and depression symptoms in cancer patients. Internet-based interventions may be one way to support effective self-care strategies to improve emotional well-being and health-related quality of life.

    OBJECTIVE:

    The aim of this study was to describe the development and acceptance of an Internet-based program intended to support cancer patients with anxiety and depression symptoms.

    METHODS:

    A structured collaboration between patients, clinicians, and researchers was used to develop a theory- and evidence-based interactive health communication application (IHCA) based on Orem's self-care deficit nursing theory with influences from Bandura's social learning theory and psychoeducation.

    RESULTS:

    The result is an IHCA described as a Nurse-led, Internet-based Learning and Self-care program that helps patients to perform self-care using different types of material in interaction with patients and healthcare staff. The acceptance of the program is consistent with the results of similar studies.

    CONCLUSIONS:

    Collaboration between patients, clinicians, and researchers seems to be a fruitful approach in the development of an IHCA aiming to support cancer patients' self-care strategies. Well-designed intervention studies are needed to evaluate the effects of the IHCA.

    IMPLICATIONS FOR PRACTICE:

    This article suggests a theoretical foundation for an IHCA and allows researchers and healthcare providers to take part in the discussion regarding format and content of IHCAs.

  • 113.
    Hedegaard, Jakob
    et al.
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Lamy, Philippe
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Nordentoft, Iver
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Algaba, Ferran
    Univ Autonoma Barcelona, Fundacio Puigvert, Sect Pathol, Barcelona 08025, Spain..
    Hoyer, Soren
    Aarhus Univ Hosp, Dept Pathol, DK-8000 Aarhus, Denmark..
    Ulhoi, Benedicte Parm
    Aarhus Univ Hosp, Dept Pathol, DK-8000 Aarhus, Denmark..
    Vang, Soren
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Reinert, Thomas
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Hermann, Gregers G.
    Frederiksberg Univ Hosp, Dept Urol, DK-2000 Frederiksberg, Denmark..
    Mogensen, Karin
    Frederiksberg Univ Hosp, Dept Urol, DK-2000 Frederiksberg, Denmark..
    Thomsen, Mathilde Borg Houlberg
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Nielsen, Morten Muhlig
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Marquez, Mirari
    Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain..
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Aine, Mattias
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, S-22100 Lund, Sweden..
    Hoglund, Mattias
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, S-22100 Lund, Sweden..
    Birkenkamp-Demtroder, Karin
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Fristrup, Niels
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Borre, Michael
    Aarhus Univ Hosp, Dept Urol, DK-8200 Aarhus, Denmark..
    Hartmann, Arndt
    Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, D-91054 Erlangen, Germany..
    Stoehr, Robert
    Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, D-91054 Erlangen, Germany..
    Wach, Sven
    Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, D-91054 Erlangen, Germany..
    Keck, Bastian
    Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, D-91054 Erlangen, Germany..
    Seitz, Anna Katharina
    Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, D-81675 Munich, Germany..
    Nawroth, Roman
    Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, D-81675 Munich, Germany..
    Maurer, Tobias
    Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, D-81675 Munich, Germany..
    Tulic, Cane
    Univ Belgrade, Clin Ctr Serbia, Clin Urol, Fac Med, Belgrade 11000, Serbia..
    Simic, Tatjana
    Univ Belgrade, Fac Med, Inst Med & Clin Biochem, Belgrade 11000, Serbia..
    Junker, Kerstin
    Univ Saarland, Dept Urol, D-66421 Homburg, Germany..
    Horstmann, Marcus
    Univ Jena, Dept Urol, D-07737 Jena, Germany..
    Harving, Niels
    Aalborg Univ Hosp, Dept Urol, DK-9000 Aalborg, Denmark..
    Petersen, Astrid Christine
    Aalborg Univ Hosp, Dept Pathol, DK-9000 Aalborg, Denmark..
    Luz Calle, M.
    Univ Vic, Dept Syst Biol, Barcelona 08500, Spain..
    Steyerberg, Ewout W.
    Erasmus MC, Dept Publ Hlth, NL-3015 CE Rotterdam, Netherlands..
    Beukers, Willemien
    Erasmus MC, Dept Pathol, NL-3015 CE Rotterdam, Netherlands..
    van Kessel, Kim E. M.
    Erasmus MC, Dept Pathol, NL-3015 CE Rotterdam, Netherlands..
    Jensen, Jorgen Bjerggaard
    Aarhus Univ Hosp, Dept Urol, DK-8200 Aarhus, Denmark..
    Pedersen, Jakob Skou
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malats, Nuria
    Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain..
    Real, Francisco X.
    Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain.;Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona 08003, Spain..
    Zwarthoff, Ellen C.
    Erasmus MC, Dept Pathol, NL-3015 CE Rotterdam, Netherlands..
    Orntoft, Torben Falck
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Dyrskjot, Lars
    Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark..
    Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma2016Ingår i: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 30, nr 1, s. 27-42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.

  • 114.
    Helenius, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Brekkan, Einar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Dahlman, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lönnemark, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Magnusson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Bladder cancer detection in patients with gross haematuria: Computed tomography urography with enhancement triggered scan versus flexible cystoscopy2015Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, nr 5, s. 377-381Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    Computed tomography urography (CTU) can be used to direct further investigation of patients if the bladder tumour detection rate is high. The aim of this study was to compare a CTU protocol including an enhancement-triggered scan and flexible cystoscopy for detecting bladder tumours.

    Materials and methods

    Patients with gross haematuria undergoing CTU during 2005–2008 were included. For patients younger than 50 years the CTU protocol included unenhanced, enhancement-triggered corticomedullary, and excretory phases. Patients older than 50 years followed the same protocol plus a nephrographic phase. The entire urinary tract was examined in all phases.

    Results

    Of 435 patients, 55 patients were diagnosed with bladder tumour. CTU detected bladder tumour in 48 patients (87%). Five CTU examination reports were false positive. With CTU, sensitivity for finding bladder tumour was 0.87, specificity 0.99, positive predictive value (PPV) 0.91 and negative predictive value (NPV) 0.98. Cystoscopy detected bladder tumour in 48 patients (87%) and had one false-positive finding, resulting in sensitivity of 0.87, specificity 1.0, PPV 0.98 and NPV 0.98.

    Conclusions

    The detection rate of bladder tumours for the CTU protocol including an enhancement-triggered scan was high and comparable to flexible cystoscopy. Hence, this protocol could be used to assess the bladder as the primary investigation and direct further investigation of the patient.

  • 115.
    Helenius, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Dahlman, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lönnemark, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Brekkan, Einar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Wernroth, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Magnusson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Comparison of post contrast CT urography phases in bladder cancer detection2016Ingår i: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 26, nr 2, s. 585-591Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives The aim of this study was to investigate which post-contrast phase(s) in a four-phase CT urography protocol is (are) most suitable for bladder cancer detection. Methods The medical records of 106 patients with visible haematuria who underwent a CT urography examination, including unenhanced, enhancement-triggered corticomedullary (CMP), nephrographic (NP) and excretory (EP) phases, were reviewed. The post-contrast phases (n = 318 different phases) were randomized into an evaluation order and blindly reviewed by two uroradiologists. Results Twenty-one patients were diagnosed with bladder cancer. Sensitivity for bladder cancer detection was 0.95 in CMP, 0.83 in NP and 0.81 in EP. Negative predictive value (NPV) was 0.99 in CMP, 0.96 in NP and 0.95 in EP. The sensitivity was higher in CMP than in both NP (p-value 0.016) and EP (p-value 0.0003). NPV was higher in CMP than in NP (p-value 0.024) and EP (p-value 0.002). Conclusion In the CT urography protocol with enhancement-triggered scan, sensitivity and NPV were highest in the corticomedullary phase, and this phase should be used for bladder assessment.

  • 116.
    Hellman, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ladjevardi, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Åkerström, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Elvin, A
    Radiofrequency tissue ablation using colled tip for liver metastases of endocrine tumors2002Ingår i: World J Surg, Vol. 26, s. 1052-Artikel i tidskrift (Refereegranskat)
  • 117.
    Hellström, Vivan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Tufveson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Wallgren, Anna Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Loskog, Angelica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Larsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Töttermann, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Bengtsson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Laurell, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Lundberg, Christina
    Holmström, Benny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Lorant, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Donor-derived and BK virus positive urologic cancers after renal transplantationManuskript (preprint) (Övrigt vetenskapligt)
  • 118.
    Hemdan, Tammer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Prognostic and Predictive Factors in Bladder Cancer2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Bladder cancer is a potentially curable malignancy; however in regards to the state of current therapy regimens, a plateau has been reached in both the non-muscle and muscle invasive types. To obtain effective treatment, and consequently a decreased mortality, it has become imperative to test and understand aspects affecting therapy response. The aim of this thesis is to illustrate a better understanding of clinical factors affecting therapy response using new drug combinations and new tumor markers alongside established risk criteria. In Paper I we reported the 5 year follow up from a multicenter, prospectively randomized study and we evaluated the 5-year outcomes of BCG alone compared to a combination of epirubicin and interferon-a2b in the treatment of patients with T1 bladder cancer. Treatment, tumor size and tumor status at second resection were independent variables associated with recurrence. Concomitant Cis was not predictive of failure of BCG therapy. Independent factor for treatment failure was remaining T1 stage at second resection. In Paper II &III we investigated the validity of emmprin, survivin and CCTα proteins as biomarkers for response and survival before neoadjuvant cisplatin chemotherapy. Bladder tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry (IHC). Patients in the chemotherapy cohort with negative emmprin and CCTα expression had significantly better overall survival (OS) than those with positive expression. In Paper IV primary end point was examining STMN1 as prognostic factor in bladder cancer.  Analysis was performed on three bladder cancer patient cohorts using IHC, western blot and a bladder cancer cell line. High levels of STMN1, expression correlated to shorter disease-specific survival and the growth and migration of the cells were significantly reduced when transfecting the cells with STMN1 siRNA. Conclusion Risk assessment and predictors of outcomes could help in individualized treatment and follow up.  Biomarkers will become more important for treatment choices in bladder cancer management.

    Delarbeten
    1. Five year outcome of a randomized prospective study comparing bacillus Calmette-Guerin with epirubicin and interferon α 2b in patients with T1 bladder cancer
    Öppna denna publikation i ny flik eller fönster >>Five year outcome of a randomized prospective study comparing bacillus Calmette-Guerin with epirubicin and interferon α 2b in patients with T1 bladder cancer
    Visa övriga...
    2014 (Engelska)Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, nr 5, s. 1244-1249Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    PURPOSE:

    In a multicenter, prospectively randomized study we evaluated the five-year outcome of bacillus Calmette-Guérin (BCG) alone compared to a combination of epirubicin and interferon α 2b in the treatment of patients with T1 bladder cancer.

    MATERIAL AND METHODS:

    The transurethral resection was followed by a second resection and bladder mapping. Stratification was for grade and cancer in situ. Follow-up entailed regular cystoscopy and cytology during the first 5 years. The end points assessed in this analysis were recurrence-free survival, time to failure of the treatment and progression, cancer-specific survival, and prognostic factors.

    RESULTS:

    The study recruited 250 eligible patients.The five years recurrence-free survival were 38% in the combination arm and 59% in the BCG arm (p=0.001). The corresponding rates for the other endpoints were not significantly different; free of - progression 78 and 77%, - treatment failure 75 and 75% and cancer-specific survival 90 and 92%. The type of treatment, size and tumour status at second resection were independent variables associated with recurrence. Concomitant carcinoma in situ was not predictive of failure of BCG therapy. Independent factor for treatment failure was remaining T1 stage at second resection.

    CONCLUSIONS:

    BCG therapy was more effective than the tested combination. Presently recommended management with second resection and three week maintenance BCG entails a low risk of cancer specific death. More aggressive treatment in patients with infiltrative tumours at second resection might improve these results. In particular, concomitant carcinoma in situ was not a predictive factor for poor outcome after BCG therapy.

    Nationell ämneskategori
    Urologi och njurmedicin
    Identifikatorer
    urn:nbn:se:uu:diva-211159 (URN)10.1016/j.juro.2013.11.005 (DOI)000335147100010 ()24231843 (PubMedID)
    Tillgänglig från: 2013-11-20 Skapad: 2013-11-20 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    2. Emmprin Expression Predicts Response and Survival following Cisplatin Containing Chemotherapy for Bladder Cancer: A Validation Study.
    Öppna denna publikation i ny flik eller fönster >>Emmprin Expression Predicts Response and Survival following Cisplatin Containing Chemotherapy for Bladder Cancer: A Validation Study.
    2015 (Engelska)Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, nr 6, s. 1575-1581Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    PURPOSE: Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response.

    MATERIALS AND METHODS: Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry.

    RESULTS: Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p <0.001). The values for cancer specific survival were 76% and 56%, respectively (p <0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p = 0.23) or cancer specific survival (55% vs 51%, p = 0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials.

    CONCLUSIONS: Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression.

    Nyckelord
    urinary bladder neoplasms; antigens, CD147; drug therapy; cystectomy; biological markers
    Nationell ämneskategori
    Medicin och hälsovetenskap Urologi och njurmedicin Cancer och onkologi
    Identifikatorer
    urn:nbn:se:uu:diva-266544 (URN)10.1016/j.juro.2015.06.085 (DOI)000365985900012 ()26119672 (PubMedID)
    Forskningsfinansiär
    Cancerfonden
    Tillgänglig från: 2015-11-10 Skapad: 2015-11-10 Senast uppdaterad: 2017-12-01Bibliografiskt granskad
    3. Choline Phosphate Cytidylyltransferase-α (CCT-α) a Novel Predictor of Response to Cisplatin Neoadjuvant Chemotherapy in Urothelial Cancer of the Bladder
    Öppna denna publikation i ny flik eller fönster >>Choline Phosphate Cytidylyltransferase-α (CCT-α) a Novel Predictor of Response to Cisplatin Neoadjuvant Chemotherapy in Urothelial Cancer of the Bladder
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Urologi och njurmedicin
    Identifikatorer
    urn:nbn:se:uu:diva-282609 (URN)
    Tillgänglig från: 2016-04-05 Skapad: 2016-04-05 Senast uppdaterad: 2016-05-12
    4. The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer
    Öppna denna publikation i ny flik eller fönster >>The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer
    Visa övriga...
    2014 (Engelska)Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 111, nr 6, s. 1180-1187Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background:The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we aim to investigate its clinical significance in urinary bladder cancer and its possibilities as a therapeutic target.Methods:Immunohistochemical analyses of STMN1 protein expression were performed in three patient cohorts: cohort I (n=115 Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90 T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular expression using siRNA.Results:In cohort I, high STMN1 expression correlated to shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04-2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients were STMN1-positive in both the primary tumour and matched metastases. In vitro, the growth and migration of the T24 cells were significantly reduced (P<0.01, P<0.0001, respectively), when transfecting the cells with STMN1-siRNA.Conclusions:STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer. 

    Nationell ämneskategori
    Medicin och hälsovetenskap Kemi
    Identifikatorer
    urn:nbn:se:uu:diva-231186 (URN)10.1038/bjc.2014.427 (DOI)000341910900018 ()25072257 (PubMedID)
    Forskningsfinansiär
    Cancerfonden
    Anmärkning

    De två första författarna delar första författarskapet.

    Tillgänglig från: 2014-09-05 Skapad: 2014-09-05 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
  • 119.
    Hemdan, Tammer
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Johansson, Robert
    Jahnson, Staffan
    Hellstrom, Pekka
    Tasdemir, Ilker
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Five-year results of nordic T1G2-3, a randomized trial comparing bcg with epirubicin and interferon alpha 2b2013Ingår i: SCANDINAVIAN JOURNAL OF UROLOGY, ISSN 2168-1805, Vol. 47, nr S219, s. 19-20Artikel i tidskrift (Övrigt vetenskapligt)
  • 120.
    Hemdan, Tammer
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Johansson, Robert
    Jahnson, Staffan
    Hellström, Pekka
    Tasdemir, Ilker
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Five year outcome of a randomized prospective study comparing bacillus Calmette-Guerin with epirubicin and interferon α 2b in patients with T1 bladder cancer2014Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, nr 5, s. 1244-1249Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE:

    In a multicenter, prospectively randomized study we evaluated the five-year outcome of bacillus Calmette-Guérin (BCG) alone compared to a combination of epirubicin and interferon α 2b in the treatment of patients with T1 bladder cancer.

    MATERIAL AND METHODS:

    The transurethral resection was followed by a second resection and bladder mapping. Stratification was for grade and cancer in situ. Follow-up entailed regular cystoscopy and cytology during the first 5 years. The end points assessed in this analysis were recurrence-free survival, time to failure of the treatment and progression, cancer-specific survival, and prognostic factors.

    RESULTS:

    The study recruited 250 eligible patients.The five years recurrence-free survival were 38% in the combination arm and 59% in the BCG arm (p=0.001). The corresponding rates for the other endpoints were not significantly different; free of - progression 78 and 77%, - treatment failure 75 and 75% and cancer-specific survival 90 and 92%. The type of treatment, size and tumour status at second resection were independent variables associated with recurrence. Concomitant carcinoma in situ was not predictive of failure of BCG therapy. Independent factor for treatment failure was remaining T1 stage at second resection.

    CONCLUSIONS:

    BCG therapy was more effective than the tested combination. Presently recommended management with second resection and three week maintenance BCG entails a low risk of cancer specific death. More aggressive treatment in patients with infiltrative tumours at second resection might improve these results. In particular, concomitant carcinoma in situ was not a predictive factor for poor outcome after BCG therapy.

  • 121.
    Hemdan, Tammer
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Lindén, Mårten
    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.
    Namuduri, Arvind Venkat
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Sjöstedt, Evelina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    de la Torre, Manuel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Gårdmark, Truls
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Asplund, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stathmin-1 is a promising prognostic factor and potential therapeutic target in urinary bladder cancerManuskript (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.

  • 122.
    Hemdan, Tammer
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Lindén, Mårten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Lind, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Namuduri, Arvind
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Sjöstedt, Evelina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    D de Ståhl, T
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Asplund, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer2014Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 111, nr 6, s. 1180-1187Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we aim to investigate its clinical significance in urinary bladder cancer and its possibilities as a therapeutic target.Methods:Immunohistochemical analyses of STMN1 protein expression were performed in three patient cohorts: cohort I (n=115 Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90 T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular expression using siRNA.Results:In cohort I, high STMN1 expression correlated to shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04-2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients were STMN1-positive in both the primary tumour and matched metastases. In vitro, the growth and migration of the T24 cells were significantly reduced (P<0.01, P<0.0001, respectively), when transfecting the cells with STMN1-siRNA.Conclusions:STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer. 

  • 123.
    Hemdan, Tammer
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Jahnson, Staffan
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Emmprin Expression Predicts Response and Survival following Cisplatin Containing Chemotherapy for Bladder Cancer: A Validation Study.2015Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, nr 6, s. 1575-1581Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response.

    MATERIALS AND METHODS: Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry.

    RESULTS: Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p <0.001). The values for cancer specific survival were 76% and 56%, respectively (p <0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p = 0.23) or cancer specific survival (55% vs 51%, p = 0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials.

    CONCLUSIONS: Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression.

  • 124.
    Hemdan, Tammer
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Turker, Polat
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Choline-phosphate cytidylyltransferase-alpha as a possible predictor of survival and response to cisplatin neoadjuvant chemotherapy in urothelial cancer of the bladder2018Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 3, s. 200-205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The aim of this study was to test choline-phosphate cytidylyltransferase-alpha (CCT-alpha) protein as a biomarker for neoadjuvant cisplatin chemotherapy response in a bladder tumor setting. Materials and methods: A total of 238 patients with T2-T4 bladder cancer enrolled into two prior randomized trials comparing neoadjuvant cisplatin-based chemotherapy (NAC) plus cystectomy with cystectomy only (no-NAC) were used as discovery and validation cohorts. Protein expression was determined with immunohistochemistry and assessed with Histo (H)-scoring. Results: In the discovery cohort, comprising 61 patients, the survival ratio after NAC treatment for CCT-alpha-negative patients was significantly increased (p = 0.001) while there was no survival advantage in the CCT-alpha-positive patient group. Similarly, in the validation cohort with 177 patients, NAC treatment improved survival only in the CCT-alpha-negative group (p = 0.006). Although there was a tendency for a good NAC response with negative CCT-alpha status, the interaction variable between biomarker and treatment was not significant (p = 0.24). In the cystectomy-only group, patients with positive CCT-alpha expression had a better survival than CCT-alpha-negative patients. This prognostic effect of CCT-alpha expression remained significant after adjusting for well-known prognostic factors in a multivariate analysis. In a pooled database of both patient data sets, multivariate analyses showed CCT-alpha status as an independent factor for overall survival (p = 0.018; hazard ratio = 1.80, 95% confidence interval 1.11-2.93). Conclusion: CCT-alpha status was not predictive of outcome of NAC response; however, in the control group with cystectomy only it was found to have prognostic value.

  • 125.
    Holfeld, Aleš
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Valdés, Alberto
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bergström Lind, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Parallel Proteomic Workflow for Mass Spectrometric Analysis of Tissue Samples Preserved by Different Methods2018Ingår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, nr 9, s. 5841-5849Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Formalin-fixed and paraffin-embedded (FFPE) and optimal cutting temperature (OCT)-embedded and frozen tissue specimens in biobanks are highly valuable in clinical studies but proteomic and post-translational modification (PTM) studies using mass spectrometry (MS) have been limited due to structural arrangement of proteins and contaminations from embedding material. This study aims to develop a parallel proteomic workflow for FFPE and OCT/frozen samples that allows for large-scale, quick, reproducible, qualitative, and quantitative high-resolution MS analysis. The optimized protocol gives details on removal of embedding material, protein extraction, and multienzyme digestion using filter-aided sample preparation method. The method was evaluated by investigating the protein expression levels in nonmuscle-invasive and muscle-invasive bladder cancer samples in two cohorts and MS spectra were carefully reviewed for contaminations. More than 2000 and 3000 proteins in FFPE and OCT/frozen samples, respectively, were identified, and samples could be clustered in different tumor stages based on their protein expression. Furthermore, more than 250 and 400 phosphopeptides could be identified from specific patient samples of FFPE and OCT/frozen, respectively, using titanium dioxide enrichment. The paper presents unique data describing the similarities and differences observed in FFPE and OCT/frozen samples and shows the feasibility to detect proteins and site-specific phosphorylation even after long-term storage of clinical samples.

  • 126.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Garmo, Hans
    Palmgren, Juni
    Norlén, Bo Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Prognostic markers under watchful waiting and radical prostatectomy2006Ingår i: Hematology/Oncology Clinics of North America, ISSN 0889-8588, E-ISSN 1558-1977, Vol. 20, nr 4, s. 845-855Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A suitable setting to analyze factors that determine prognosis or treatment response in prostate cancer is an unbiased comparison of radical prostatectomy and watchful waiting as in the Scandinavian Prostate Cancer Group Trial number 4. In our previous presentation of 10-year results, we studied Gleason score, serum prostate-specific antigen (PSA) at diagnosis, and age at diagnosis as modifiers of the effect of radical prostatectomy on survival. Because overall prognostic information obtained by these parameters or by tumor stage was not provided in our publication, we now present these data in the two study arms separately.

  • 127.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Helgesen, Fred
    Salo, Jaakko O.
    Folmerz, Per
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Andersson, Swen-Olof
    Spångberg, Anders
    Busch, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Nordling, Steg
    Palmgren, Juni
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Norlén, Bo Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer2002Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 347, nr 11, s. 781-789Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Radical prostatectomy is widely used in the treatment of early prostate cancer. The possible survival benefit of this treatment, however, is unclear. We conducted a randomized trial to address this question. METHODS: From October 1989 through February 1999, 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b, T1c, or T2 were randomly assigned to watchful waiting or radical prostatectomy. We achieved complete follow-up through the year 2000 with blinded evaluation of causes of death. The primary end point was death due to prostate cancer, and the secondary end points were overall mortality, metastasis-free survival, and local progression. RESULTS: During a median of 6.2 years of follow-up, 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died (P=0.31). Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting (8.9 percent) and in 16 of 347 of those assigned to radical prostatectomy (4.6 percent) (relative hazard, 0.50; 95 percent confidence interval, 0.27 to 0.91; P=0.02). Death due to other causes occurred in 31 of 348 men in the watchful-waiting group (8.9 percent) and in 37 of 347 men in the radical-prostatectomy group (10.6 percent). The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting (relative hazard, 0.63; 95 percent confidence interval, 0.41 to 0.96). CONCLUSIONS: In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival.

  • 128.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Steineck, Gunnar
    Garmo, Hans
    Palmgren, Juni
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Results from the scandinavian prostate cancer group trial number 4: a randomized controlled trial of radical prostatectomy versus watchful waiting2012Ingår i: Journal of the National Cancer Institute. Monographs, ISSN 1052-6773, E-ISSN 1745-6614, Vol. 2012, nr 45, s. 230-233Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the Scandinavian Prostate Cancer Group Trial Number 4 (SPCG-4), 347 men were randomly assigned to radical prostatectomy and 348 to watchful waiting. In the most recent analysis (median follow-up time = 12.8 years), the cumulative mortality curves had been stable over the follow-up. At 15 years, the absolute risk reduction of dying from prostate cancer was 6.1% following randomization to radical prostatectomy, compared with watchful waiting. Hence, 17 need to be randomized to operation to avert one death. Data on self-reported symptoms, stress from symptoms, and quality of life were collected at 4 and 12.2 years of median follow-up. These questionnaire studies show an intricate pattern of symptoms evolving after surgery, hormonal treatments, signs of tumor progression, and also from natural aging. This article discusses some of the main findings of the SPCG-4 study.

  • 129. Hugosson, j
    et al.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Kvaliteten på radikal prostatektomi måste säkerställas - Fortlöpande förbättringsarbete behövs på varje klinik: med patientenkäter kan enskilda kirurgers resultat följas upp2017Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518Artikel i tidskrift (Refereegranskat)
  • 130. Hägglöf, Christina
    et al.
    Hammarsten, Peter
    Strömvall, Kerstin
    Egevad, Lars
    Josefsson, Andreas
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Granfors, Torvald
    Bergh, Anders
    TMPRSS2-ERG expression predicts prostate cancer survival and associates with stromal biomarkers.2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 2, artikel-id e86824Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The TMPRSS2-ERG gene fusion is found in approximately half of all prostate cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified. Expression of ERG was also associated with clinical markers such as advanced tumor stage, high Gleason score, presence of metastasis and prognostic tumor cell markers such as high Ki67, pEGFR and pAkt. Novel associations between TMPRSS2-ERG and alterations in the tumor stroma, for example, increased vascular density, hyaluronan and PDGFRβ and decreased Caveolin-1, all known to be associated with an aggressive disease, were found. The present study suggests that the TMPRSS2-ERG fusion gene is associated with a more aggressive prostate cancer phenotype, supported by changes in the tumor stroma.

  • 131.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, Umea, Sweden.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden.
    de Luna, Xavier
    Umea Univ, Dept Stat, USBE, Umea, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Söderkvist, Karin
    Umea Univ, Dept Radiat Sci, Oncol, Umea, Sweden.
    Aljabery, Firas
    Linkoping Univ, Div Urol, Dept Clin & Expt Med, Linkoping, Sweden.
    Ströck, Viveka
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Dept Urol, Stockholm, Sweden.
    Gårdmark, Truls
    Danderyd Hosp, Dept Clin Sci, Karolinska Inst, Stockholm, Sweden.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Jahnson, Staffan
    Linkoping Univ, Div Urol, Dept Clin & Expt Med, Linkoping, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Dept Urol, Malmo, Sweden;Lund Univ, Dept Translat Med, Malmo, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer: A Swedish nationwide population-based cohort study2019Ingår i: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, nr 5, s. 2196-2204Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Studies of survival comparing radical cystectomy (RC) and radiotherapy for muscle-invasive bladder cancer have provided inconsistent results and have methodological limitations. The aim of the study was to investigate risk of death after radiotherapy as compared to RC.

    Methods: We selected patients with muscle-invasive urothelial carcinoma without distant metastases, treated with radiotherapy or RC from 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe) and estimated absolute and relative risk of bladder cancer death and all-cause death. In a group of patients, theoretically eligible for a trial comparing radiotherapy and RC, we calculated risk difference in an instrumental variable analysis. We have not investigated chemoradiotherapy as this treatment was not used in the study time period.

    Results: The study included 3 309 patients, of those 17% were treated with radiotherapy and 83% with RC. Patients treated with radiotherapy were older, had more advanced comorbidity, and had a higher risk of death as compared to patients treated with RC (relative risks of 1.5-1.6). In the "trial population," all-cause death risk difference was 6 per 100 patients lower after radiotherapy at 5 years of follow-up, 95% confidence interval -41 to 29.

    Conclusion(s): Patient selection between the treatments make it difficult to evaluate results from conventionally adjusted and propensity-score matched survival analysis. When taking into account unmeasured confounding by instrumental variable analysis, no differences in survival was found between the treatments for a selected group of patients. Further clinical studies are needed to characterize this group of patients, which can serve as a basis for future comparison studies for treatment recommendations.

  • 132.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, S-90185 Umea, Sweden;Umea Univ, Dept Publ Hlth & Clin Med, Nutr Res, Umea, Sweden.
    Jonsson, Håkan
    Umea Univ, Dept Radiat Sci, Umea, Sweden.
    Björge, Tone
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway;Canc Registry Norway, Oslo, Norway.
    Nagel, Gabriele
    Ulm Univ, Inst Epidemiol & Med Biometry, Ulm, Germany;Agcy Prevent & Social Med, Vorarlberg Canc Registry, Bregenz, Aks, Austria.
    Manjer, Jonas
    Lund Univ, Skane Univ Hosp, Dept Surg, Malmo, Sweden.
    Ulmer, Hanno
    Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Innsbruck, Austria.
    Drake, Isabel
    Lund Univ, Dept Clin Sci Malmo, Lund, Sweden.
    Ghaderi, Sara
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
    Lang, Alois
    Agcy Prevent & Social Med, Vorarlberg Canc Registry, Bregenz, Aks, Austria.
    Engeland, Anders
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway;Norwegian Inst Publ Hlth, Bergen, Norway.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stocks, Tanja
    Lund Univ, Dept Clin Sci Lund, Lund, Sweden.
    Linear age-course effects on the associations between body mass index, triglycerides, and female breast and male liver cancer risk: An internal replication study of 800,000 individuals2020Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, nr 1, s. 58-67Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Apart from the consistently observed differential association between obesity and breast cancer risk by menopausal status, the associations between obesity and other metabolic imbalances with risks of cancers have not been systematically investigated across the age-course. We created two random 50-50% cohorts from six European cohorts comprising 813,927 individuals. In the "discovery cohort", we used Cox regression with attained age as time-scale and tested interactions between body mass index (BMI), blood pressure, plasma glucose, triglycerides and cholesterol, and attained age in relation to cancer risk. Results with a p-value below 0.05 were additionally tested in the "replication cohort" where a replicated result was considered evidence of a linear interaction with attained age. These findings were investigated by flexible parametric survival models for any age-plateaus in their shape of associations with cancer risk across age. Consistent with other studies, BMI was negatively related to breast cancer risk (n cases = 11,723) among younger (premenopausal) women. However, the association remained negative for several years after menopause and, although gradually weakening over age, the association became positive only at 62 years of age. This linear and positive age-interaction was also found for triglycerides and breast cancer, and for BMI and triglycerides in relation to liver cancer among men (n cases = 444). These findings are unlikely to be due to chance owing to the replication. The linear age-interactions in breast cancer may suggest an influence by other age-related factors than menopause; however, further investigation of age-related effect modifiers in both breast and liver cancer is needed.

  • 133.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umeå University, Department of Biobank Research.
    Liedberg, Fredrik
    Skåne University Hospital, Department of Urology; Lund University, Department of Translational Medicine.
    Hagberg, Oskar
    Regional Cancer Centre South, Lund.
    Aljabery, Firas
    Linköping University, Division of Urology, Department of Clinical and Experimental Medicine.
    Ströck, Viveka
    Sahlgrenska University Hospital, Department of Urology.
    Hosseini, Abolfazl
    Karolinska University Hospital, Department of Urology.
    Gårdmark, Truls
    Karolinska Institute, Danderyd Hospital, Department of Clinical Sciences.
    Sherif, Amir
    Umeå University, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Garmo, Hans
    King’s College London, Faculty of Life Sciences and Medicine, Division of Cancer Studies; Regional Cancer Centre Uppsala/Örebro.
    Jahnson, Staffan
    Linköping University, Division of Urology, Department of Clinical and Experimental Medicine.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. King’s College London, Faculty of Life Sciences and Medicine, Division of Cancer Studies.
    Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)2017Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, nr 9, artikel-id e016606Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe).

    Participants: The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death.

    Findings to date: Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival.

    Future plans: The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author.

  • 134.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.;Umea Univ, Dept Biobank Res, S-90185 Umea, 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..
    Stocks, Tanja
    Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.;Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Lund, Sweden..
    Garmo, Hans
    Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden.;Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England..
    Holmberg, Lars
    Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden.;Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England..
    Van Hemelrijck, Mieke
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England.;Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Interpretation of conventional survival analysis and competing-risk analysis: an example of hypertension and prostate cancer2016Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, nr 6, s. 850-852Artikel i tidskrift (Övrigt vetenskapligt)
  • 135. Häggström, Christel
    et al.
    Stocks, Tanja
    Nagel, Gabriele
    Manjer, Jonas
    Bjørge, Tone
    Hallmans, Göran
    Engeland, Anders
    Ulmer, Hanno
    Lindkvist, Björn
    Selmer, Randi
    Concin, Hans
    Tretli, Steinar
    Jonsson, Håkan
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations2014Ingår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 25, nr 6, s. 823-828Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes.

    METHODS: In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score.

    RESULTS: During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%.

    CONCLUSIONS: In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate canc