Change search
Refine search result
123 1 - 50 of 114
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Aizawa, Naoki
    et al.
    University of Tokyo, Japan.
    Gandaglia, Giorgio
    IRCCS, Italy; Lund University, Sweden.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Fujimura, Tetsuya
    University of Tokyo, Japan.
    Fukuhara, Hiroshi
    University of Tokyo, Japan.
    Montorsi, Francesco
    IRCCS, Italy.
    Homma, Yukio
    University of Tokyo, Japan.
    Igawa, Yasuhiko
    University of Tokyo, Japan.
    URB937, a peripherally restricted inhibitor for fatty acid amide hydrolase, reduces prostaglandin E-2-induced bladder overactivity and hyperactivity of bladder mechano-afferent nerve fibres in rats2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 5, p. 821-828Article in journal (Refereed)
    Abstract [en]

    Objective To determine if inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) can counteract the changes in urodynamic variables and bladder afferent activities induced by intravesical prostaglandin E-2 (PGE(2)) instillation in rats. Materials and methods In female Sprague-Dawley rats we studied the effects of URB937, a peripherally restricted FAAH inhibitor, on single-unit afferent activity (SAA) during PGE(2)-induced bladder overactivity (BO). SAA measurements were made in urethane-anaesthetised rats and Ad-and C-fibres were identified by electrical stimulation of the pelvic nerve and by bladder distention. Cystometry (CMG) in conscious animals and during SAA measurements was performed during intravesical instillation of PGE(2) (50 or 100 mu M) after intravenous administration of URB937 (0.1 and 1 mg/kg) or vehicle. In separate experiments, the comparative expressions of FAAH and cannabinoid receptors, CB1 and CB2, in microsurgically removed L6 dorsal root ganglion (DRG) were studied by immunofluorescence. Results During CMG, 1 mg/kg URB937, but not vehicle or 0.1 mg/kg URB937, counteracted the PGE(2)-induced changes in urodynamic variables. PGE(2) increased the SAAs of C-fibres, but not Ad-fibres. URB937 (1 mg/kg) depressed Ad-fibre SAA and abolished the facilitated C-fibre SAA induced by PGE(2). The DRG nerve cells showed strong staining for FAAH, CB1 and CB2, with a mean (SEM) of 77 (2)% and 87 (3)% of FAAH-positive nerve cell bodies co-expressing CB1 or CB2 immunofluorescence, respectively. Conclusion The present results show that URB937, a peripherally restricted FAAH inhibitor, reduces BO and C-fibre hyperactivity in the rat bladder provoked by PGE(2), suggesting an important role of the peripheral endocannabinoid system in BO and hypersensitivity.

  • 2.
    Aljabery, Firas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Breast and Endocrine Surgery, Karolinska University Hospital, Solna Stockholm, Sweden .
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Jahnson, Staffan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology.
    Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.2017In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 120, no 3, p. 329-336Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

    PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

    RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

    CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

  • 3. Asplund, Ragnar
    et al.
    Marnetoft, Sven-Uno
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Selander, John
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Åkerström, Bengt
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Nocturia in relation to somatic health, mental health and pain in adult men and women2005In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 95, no 6, p. 816-819Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess the relationship of nocturia to somatic health, mental health and bodily pain. SUBJECTS AND METHODS: A randomly selected group of men and women aged 20-64 years, living in three small municipalities in northern Sweden, or in the city of Ostersund or in Stockholm, were sent a postal questionnaire containing questions on somatic and mental health, satisfaction with life, pain, nocturnal voiding, work and sick-listing from work. RESULTS: Reports (from 1948 respondents) on poor somatic and mental health and on pain all increased in parallel with increasing frequency of nocturnal voids. In a multiple logistic regression analysis with sex, age, somatic health, mental health and bodily pain as the independent variables, significant independent correlates (odds ratios, confidence intervals) of nocturnal micturition (two or more episodes vs none or one) were: age 45-59 vs 20-44 years, 1.9 (1.3-2.7), > or =60 vs 20-44 years, 3.8 (2.4-6.0); somatic health, poor vs good, 2.3 (1.4-3.7); mental health, poor vs good, 1.9 (1.2-3.0); pain, rather mild vs very mild or none, 1.5 (1.0-2.3); rather severe vs very mild or none, 1.9 (1.1-3.2); and very severe vs very mild or none, 6.0 (2.5-14.0). Gender was deleted by the logistic model. Sick-listing for > or = 60 days during the past year was reported by 4.9%, 10.6%, 5.6% and 38.9% of the men with none, one, two or > or = three nocturnal voids, respectively, and by 10%, 12.4%, 23% and 46.7% (both P < 0.001) of the corresponding women, respectively. Life satisfaction decreased in parallel with increased nocturia. CONCLUSION: The impairment of both somatic and mental health was associated with increased nocturnal voiding. Pain was associated with a substantial increase in nocturia after adjusting for age and somatic and mental health. Sick-leave was more common in association with more nocturnal voids.

  • 4.
    Benigni, F
    et al.
    BioXell SpA.
    Baroni, E
    BioXell SpA.
    Zecevic, M
    BioXell SpA.
    Zvara, P
    BioXell SpA.
    Streng, T
    Lund University.
    Hedlund, Petter
    Lund University.
    Colli, E
    BioXell SpA.
    DAmbrosio, D
    BioXell SpA.
    Andersson, KE
    Lund University.
    Oral treatment with a vitamin D3 analogue (BXL628) has anti-inflammatory effects in rodent model of interstitial cystitis2006In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 97, no 3, p. 617-624Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the effects of a vitamin D3 analogue (BXL628) in a model of chronic cystitis, as calcitriol analogues might be an interesting new therapeutic option for interstitial cystitis, for although the cause of the disease remains unclear, the increase in mast cells in the mucosa and detrusor muscle are significant.

    MATERIALS AND METHODS: We devised a mouse model of allergen-induced allergic cystitis that is associated with the up-regulation of genes for interleukin-13, FcepsilonRIalpha and mast cells-derived proteases, a massive inflammatory reaction in the bladder tissue, and augmented levels of mast cell-derived protease 1 (MMCP1) detected in mouse sera.

    RESULTS: Oral administration of BXL628 significantly reduced the expression of interleukin-13, FcepsilonRIalpha and MMCP1 in the bladder. Furthermore, histological analysis showed a decrease in oedema and leukocyte infiltration in the bladder wall. BXL628 treatment reduced serum MMCP1 levels, indicating an effect on mast cell degranulation in vivo.

    CONCLUSIONS: Vitamin D3 analogues may successfully be used as anti-inflammatory agents in allergen-mediated inflammatory reactions. Moreover, the modulatory effect shown on mast cell activation by the BXL628 analogue strongly supports its potential therapeutic use in a possibly mast cell-dependent disease such as human interstitial cystitis.

  • 5.
    Bivalacqua, Trinity J.
    et al.
    Brady Urological Institute, and Division of Cardiology, Department of Medicine Johns Hopkins Hospital.
    Kendirci, Muammer
    Department of Urology, Tulane University School of Medicine, New Orleans.
    Champion, Hunter C
    Brady Urological Institute, and Division of Cardiology, Department of Medicine Johns Hopkins Hospital.
    Hellstrom, Wayne J G
    Department of Urology, Tulane University School of Medicine, New Orleans.
    Andersson, Karl-Erik
    Department of Clinical Pharmacology, Lund University Hospital, Lund.
    Hedlund, Petter
    Lund University Hospital.
    Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1alpha.2007In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 99, no 6, p. 1488-1494Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the expression of cGMP-dependent protein kinase 1 (PKG1)alpha and PKG1beta in the corpus cavernosum, and to evaluate the effect of adenoviral gene transfer of PKG1alpha to the erectile compartment on erectile function in a rat model of diabetes.

    MATERIALS AND METHODS: Diabetic (DM; induced by streptozotocin) male Sprague Dawley rats were transfected with adenoviruses (AdCMVbetagal or AdCMVPKG1alpha, in 10 rats each) 2 months after the induction of DM. Intracavernosal pressure (ICP) during stimulation of the cavernosal nerve (CN) was assessed, and compared with mean arterial pressure (MAP). Erectile tissue was harvested for Western blot analysis, immunohistochemistry and total PKG activity. Ten age-matched rats without DM served as the control.

    RESULTS: Compared to controls, AdCMVbetagal-transfected DM rats had significantly lower peak ICP responses, ICP/MAP ratios, and filling rates during CN stimulation. In DM rats transfected with AdCMVPKG1alpha, peak ICP, ICP/MAP ratios and filling rates were significantly better than in DM rats transfected with the reporter gene. As assessed by Western blot and immunohistochemistry, expression of PKG1alpha and PKG1beta was lower in corporal tissue from DM AdCMVbetagal-transfected rats than in controls. PKG1alpha expression was improved after AdCMVPKG1alpha gene therapy. Total PKG activity was lower in DM rat corporal tissue than in controls, and PKG1alpha gene transfer significantly improved DM corporal PKG activity to a value greater than in the control.

    CONCLUSION: PKG1alpha and PKG1beta activities are reduced in the erectile tissue of the diabetic rat, and gene transfer of PKG1alpha to the penis restored PKG activity and erectile function in vivo in diabetic rats. Gene therapy procedures targeting PKG1alpha might be an interesting future therapeutic approach to overcome diabetic erectile dysfunction resistant to oral pharmacotherapy.

  • 6.
    Björklund, Johan
    et al.
    Karolinska Univ Hosp, Dept Urol, Solna, Sweden..
    Folkvaljon, Yasin
    Uppsala Univ Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Cole, Alexander
    Harvard Med Sch, Brigham & Womens Hosp, Div Urol Surg, Boston, MA USA..
    Carlsson, Stefan
    Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Robinson, David
    Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden.;Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Loeb, Stacy
    NYU, Dept Urol Populat Hlth, Laura & Isaac Perlmutter Canc Ctr, New York, NY USA..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Akre, Olof
    Karolinska Univ Hosp, Dept Urol, Solna, Sweden.;Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Postoperative mortality 90 days after robot-assisted laparoscopic prostatectomy and retropubic radical prostatectomy: a nationwide population-based study2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 2, p. 302-306Article in journal (Refereed)
    Abstract [en]

    Objective To assess 90-day postoperative mortality after robot-assisted laparoscopic radical prostatectomy (RARP) and retropubic radical prostatectomy (RRP) using nationwide population-based registry data. Patients and Methods We conducted a cohort study using the National Prostate Cancer Register of Sweden, including 22 344 men with localized prostate cancer of clinical stage T1-T3, whose prostate-specific antigen levels were <50 mu g/mL and who had undergone primary radical prostatectomy in the period 1998-2012. Vital status was ascertained through the Total Population Register. The rates for 90-day postoperative mortality were analysed using logistic regression analysis, and comparisons of 90-day mortality with the background population were made using standardized mortality ratios (SMRs). Results Of the 14 820 men who underwent RRP, 29 (0.20%) died, and of the 7 524 men who underwent RARP, 10 (0.13%) died. Mortality in the cohort during the 90-day postoperative period was lower than in an age-matched background population: SMR 0.57 (95% confidence interval [CI] 0.39-0.75). There was no statistically significant difference in 90-day mortality according to surgical method: RARP vs RRP odds ratio (OR) 1.14; 95% CI 0.46-2.81. Postoperative 90-day mortality decreased over time: 2008-2012 vs 1998-2007 OR 0.44; 95% CI 0.21-0.95, mainly because of lower mortality after RARP. Conclusion The 90-day postoperative mortality rates were low after RARP and RRP and there was no statistically significant difference between the methods. Given the long life expectancy among men with low-and intermediate-risk prostate cancer, very low postoperative mortality is a prerequisite for RP, which was fulfilled by both RRP and RARP. The selection of healthy men for RP is highlighted by the lower 90-day mortality after RP compared with the background population.

  • 7. Björklund, Johan
    et al.
    Folkvaljon, Yasin
    Cole, Alexander
    Carlsson, Stefan
    Robinson, David
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Ryhov County Hospital, Jönköping, Sweden.
    Loeb, Stacy
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Akre, Olof
    Postoperative mortality 90 days after robot-assisted laparoscopic prostatectomy and retropubic radical prostatectomy: a nationwide population-based study2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 2, p. 302-306Article in journal (Refereed)
    Abstract [en]

    Objective To assess 90-day postoperative mortality after robot-assisted laparoscopic radical prostatectomy (RARP) and retropubic radical prostatectomy (RRP) using nationwide population-based registry data. Patients and Methods We conducted a cohort study using the National Prostate Cancer Register of Sweden, including 22 344 men with localized prostate cancer of clinical stage T1-T3, whose prostate-specific antigen levels were <50 mu g/mL and who had undergone primary radical prostatectomy in the period 1998-2012. Vital status was ascertained through the Total Population Register. The rates for 90-day postoperative mortality were analysed using logistic regression analysis, and comparisons of 90-day mortality with the background population were made using standardized mortality ratios (SMRs). Results Of the 14 820 men who underwent RRP, 29 (0.20%) died, and of the 7 524 men who underwent RARP, 10 (0.13%) died. Mortality in the cohort during the 90-day postoperative period was lower than in an age-matched background population: SMR 0.57 (95% confidence interval [CI] 0.39-0.75). There was no statistically significant difference in 90-day mortality according to surgical method: RARP vs RRP odds ratio (OR) 1.14; 95% CI 0.46-2.81. Postoperative 90-day mortality decreased over time: 2008-2012 vs 1998-2007 OR 0.44; 95% CI 0.21-0.95, mainly because of lower mortality after RARP. Conclusion The 90-day postoperative mortality rates were low after RARP and RRP and there was no statistically significant difference between the methods. Given the long life expectancy among men with low-and intermediate-risk prostate cancer, very low postoperative mortality is a prerequisite for RP, which was fulfilled by both RRP and RARP. The selection of healthy men for RP is highlighted by the lower 90-day mortality after RP compared with the background population.

  • 8.
    Bosco, Cecilia
    et al.
    Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.
    Wong, Chloe
    Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.; Uppsala Univ, Reg Canc Ctr, Uppsala, Sweden..
    Crawley, Danielle
    Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.
    Hammar, Niklas
    Inst Environm Med, Epidemiol Unit, Stockholm, Sweden.; Global Med Affairs AstraZeneca, Med Evidence & Observat Res, Molndal, Sweden..
    Adolfsson, Jan
    Karolinska Inst, CLINTEC Dept, Stockholm, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.
    Drugs for metabolic conditions and prostate cancer death in men on GnRH agonists.2018In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 121, no 2, p. 260-267Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate whether drugs for metabolic conditions influence prostate cancer-specific mortality in men starting gonadotrophin-releasing hormone (GnRH) agonists, as it is unclear whether metabolic syndrome and its related drugs is affecting treatment response in men with prostate cancer on GnRH agonists.

    PATIENTS AND METHODS: We selected all men receiving GnRH agonists as primary treatment in the Prostate Cancer data Base Sweden (PCBaSe) (n = 9267). Use of drugs for metabolic conditions (i.e. anti-diabetes, anti-dyslipidaemia, and antihypertension) in relation to all-cause, cardiovascular disease (CVD), and prostate cancer-specific death were studied using multivariate Cox proportional hazard and Fine and Gray competing regression models.

    RESULTS: In all, 6322 (68%) men used at least one drug for a metabolic condition at GnRH agonist initiation: 46% on antihypertensive drugs only, 32% on drugs for dyslipidaemia and hypertension, and ~10% on drugs for more than two metabolic conditions. Cox models indicated a weak increased risk of prostate cancer death in men who were on drugs for hypertension only (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.03-1.23) or drugs for hyperglycaemia (HR 1.19, 95% CI 1.06-1.35) at GnRH agonist initiation. However, upon taking into account competing risk from CVD death, none of the drugs for metabolic conditions were associated with an increased risk of prostate cancer death.

    CONCLUSION: We did not find evidence for a better or worse response to GnRH agonists in men with prostate cancer who were also on drugs for hypertension, dyslipidaemia, or hyperglycaemia.

  • 9. Bratt, Ola
    et al.
    Folkvaljon, Yasin
    Loeb, Stacy
    Klotz, Laurence
    Egevad, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Upper limit of cancer extent on biopsy defining very low-risk prostate cancer2015In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 116, no 2, p. 213-219Article in journal (Refereed)
    Abstract [en]

    Objective To investigate how much Gleason pattern 3 cancer prostate biopsy specimens may contain without an increased risk of undetected more aggressive cancer, compared with the risk for cancers fulfilling the National Comprehensive Cancer Network (NCCN) criteria for very low-risk prostate cancer. Patients and Methods We identified 1286 men aged <70 years in the National Prostate Cancer Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c or T2 prostate cancer with Gleason pattern <= 3 only, prostate-specific antigen (PSA) level of <10 ng/mL and a PSA density of <0.15 ng/mL/mL. The association between the extent of cancer in the biopsies (the number and proportion of positive cores and the total cancer length in the cores in millimetres) and the likelihood of Gleason pattern 4-5 in the RP specimen was analysed with logistic regression. Results In all, 438 (34%) of the 1286 men had Gleason pattern 4-5 in the RP specimen. Increasing number and proportion of positive biopsy cores, as well as increasing biopsy cancer length were both significantly associated with increased risk of upgrading at RP in univariable analysis, but in multivariable analysis only biopsy cancer length remained significant. The 684 men with stage T1c and < 8 mm cancer had similar risk of upgrading regardless of whether the number of positive biopsy cores was 1-2 or 3-4 (28% vs 27% risk); upgrading was more common among the remaining men (40%, P < 0.01). Conclusions Men aged < 70 years with stage T1c prostate cancer and 3-4 biopsy cores with Gleason pattern 3 are not more likely to have undetected Gleason pattern 4-5 cancer than men with 1-2 cores with cancer, provided that the total biopsy cancer length is < 8 mm. We propose that the definition of very low-risk prostate cancer is widened accordingly.

  • 10.
    Bratt, Ola
    et al.
    Univ Oxford, Nuffield Dept Surg Sci, Oxford OX3 7DQ, England.;Lund Univ, Helsingborg Hosp, Dept Urol, Lund, Sweden.;Lund Univ, Helsingborg Hosp, Dept Urol, Helsingborg, Sweden..
    Folkvaljon, Yasin
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Loeb, Stacy
    NYU, Dept Urol, New York, NY USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Klotz, Laurence
    Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada..
    Egevad, Lars
    Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden..
    Upper limit of cancer extent on biopsy defining very low-risk prostate cancer2015In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 116, no 2, p. 213-219Article in journal (Refereed)
    Abstract [en]

    Objective To investigate how much Gleason pattern 3 cancer prostate biopsy specimens may contain without an increased risk of undetected more aggressive cancer, compared with the risk for cancers fulfilling the National Comprehensive Cancer Network (NCCN) criteria for very low-risk prostate cancer. Patients and Methods We identified 1286 men aged <70 years in the National Prostate Cancer Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c or T2 prostate cancer with Gleason pattern <= 3 only, prostate-specific antigen (PSA) level of <10 ng/mL and a PSA density of <0.15 ng/mL/mL. The association between the extent of cancer in the biopsies (the number and proportion of positive cores and the total cancer length in the cores in millimetres) and the likelihood of Gleason pattern 4-5 in the RP specimen was analysed with logistic regression. Results In all, 438 (34%) of the 1286 men had Gleason pattern 4-5 in the RP specimen. Increasing number and proportion of positive biopsy cores, as well as increasing biopsy cancer length were both significantly associated with increased risk of upgrading at RP in univariable analysis, but in multivariable analysis only biopsy cancer length remained significant. The 684 men with stage T1c and < 8 mm cancer had similar risk of upgrading regardless of whether the number of positive biopsy cores was 1-2 or 3-4 (28% vs 27% risk); upgrading was more common among the remaining men (40%, P < 0.01). Conclusions Men aged < 70 years with stage T1c prostate cancer and 3-4 biopsy cores with Gleason pattern 3 are not more likely to have undetected Gleason pattern 4-5 cancer than men with 1-2 cores with cancer, provided that the total biopsy cancer length is < 8 mm. We propose that the definition of very low-risk prostate cancer is widened accordingly.

  • 11.
    Brehmer, M
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Svensson, Irene
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Heat-induced apoptosis in human prostatic stromal cells2000In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 85, no 4, p. 535-541Article in journal (Refereed)
    Abstract [en]

    Objective. To determine whether heat, used in transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia and which causes necrotic lesions within the adenoma, induces apoptosis in benign human prostatic stromal cells. Materials and methods. Prostatic stromal cells were cultured from benign human prostatic tissue. The origin of the cells was identified by immunohistochemical staining and transmission electron microscopy. Cell cultures were exposed to moderate hyperthermia (47░C) for 1 h and any apoptosis detected by light microscopy, transmission electron microscopy and the measurement of induced caspase-3-like activity. Results. The cultures contained a mixed population of smooth muscle cells and myofibroblasts. Twenty-four hours after heat exposure, 76% of the cells were apoptotic and the caspase activity had increased, whereas only 14% of the cells were necrotic. Conclusion. Moderate hyperthermia induces apoptosis in cultured human prostatic stromal cells.

  • 12. Carlsson, Sigrid
    et al.
    Drevin, Linda
    Loeb, Stacy
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Franck Lissbrant, Ingela
    Robinson, David
    Johansson, Eva
    Stattin, Pär
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Nursing.
    Population-based study of long-term functional outcomes after prostate cancer treatment2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 6B, p. E36-E45Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate long-term urinary, sexual and bowel functional outcomes after prostate cancer treatment at a median follow-up of 12 years (IQR 11-13).

    PATIENTS AND METHODS: In this nationwide, population-based study, we identified from the National Prostate Cancer Register, Sweden, 6,003 men diagnosed with localized prostate cancer (clinical local stage T1-2, any Gleason score, prostate specific antigen < 20 ng/mL, NX or N0, MX or M0) between 1997 and 2002 who were ≤70 years at diagnosis. 1,000 prostate cancer-free controls were selected, matched for age and county of residence. Functional outcomes were evaluated with a validated self-reported questionnaire.

    RESULTS: Responses were obtained from 3,937/6,003 cases (66%) and 459/1,000 (46%) controls. Twelve years post diagnosis, at a median age of 75 years, the proportion of cases with adverse symptoms was 87% for erectile dysfunction or sexually inactive, 20% for urinary incontinence and 14% for bowel disturbances. The corresponding proportions for controls were 62%, 6% and 7%, respectively. Men with prostate cancer, except those on surveillance, had an increased risk of erectile dysfunction, compared to control men. Radical prostatectomy was associated with increased risk of urinary incontinence (odds ratio; OR 2.29 [95% CI 1.83-2.86] and radiotherapy increased the risk of bowel dysfunction (OR 2.46 [95% CI 1.73-3.49]) compared to control men. Multi-modal treatment, in particular including androgen deprivation therapy (ADT), was associated with the highest risk of adverse effects; for instance radical prostatectomy followed by radiotherapy and ADT was associated with an OR of 3.74 [95 CI 1.76-7.95] for erectile dysfunction and OR 3.22 [95% CI 1.93-5.37] for urinary incontinence.

    CONCLUSION: The proportion of men who suffer long-term impact on functional outcomes after prostate cancer treatment was substantial.

  • 13.
    Carlsson, Sigrid
    et al.
    Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA.;Univ Gothenburg, Sahlgrenska Acad, Dept Urol, Gothenburg, Sweden..
    Drevin, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Loeb, Stacy
    NYU, New York, NY USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Widmark, Anders
    Umea Univ, Oncol, Dept Radiat Sci, Umea, Sweden..
    Lissbrant, Ingela Franck
    Univ Gothenburg, Sahlgrenska Acad, Dept Oncol, Gothenburg, Sweden..
    Robinson, David
    Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umea, Sweden.;Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden..
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Stattin, Par
    Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umea, Sweden..
    Fransson, Per
    Umea Univ, Dept Nursing, Umea, Sweden..
    Population-based study of long-term functional outcomes after prostate cancer treatment2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 6B, p. E36-E45Article in journal (Refereed)
    Abstract [en]

    Objective To evaluate long-term urinary, sexual and bowel functional outcomes after prostate cancer treatment at a median (interquartile range) follow-up of 12 (11-13) years. Patients and Methods In this nationwide, population-based study, we identified 6 003 men diagnosed with localized prostate cancer (clinical local stage T1-2, any Gleason score, prostate-specific antigen <20 ng/mL, NX or N0, MX or M0) between 1997 and 2002 from the National Prostate Cancer Register, Sweden. The men were aged <= 70 years at diagnosis. A control group of 1 000 men without prostate cancer were also selected, matched for age and county of residence. Functional outcomes were evaluated with a validated self-reported questionnaire. Results Responses were obtained from 3 937/6 003 cases (66%) and 459/1 000 (46%) controls. At 12 years after diagnosis and at a median age of 75 years, the proportion of cases with adverse symptoms was 87% for erectile dysfunction/sexual inactivity, 20% for urinary incontinence and 14% for bowel disturbances. The corresponding proportions for controls were 62, 6 and 7%, respectively. Men with prostate cancer, except those on surveillance, had an increased risk of erectile dysfunction compared with the men in the control group. Radical prostatectomy was associated with an increased risk of urinary incontinence (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.36-2.62) and radiotherapy increased the risk of bowel dysfunction (OR 2.46, 95% CI 1.73-3.49) compared with men in the control group. Multimodal treatment, in particular treatment including androgen deprivation therapy (ADT), was associated with the highest risk of adverse effects; for instance, radical prostatectomy followed by radiotherapy and ADT was associated with an OR of 3.74 (95% CI 1.76-7.95) for erectile dysfunction and an OR of 3.22 (95% CI 1.93-5.37) for urinary incontinence. Conclusion The proportion of men who experienced a long-term impact on functional outcomes after prostate cancer treatment was substantial.

  • 14.
    Castiglione, Fabio
    et al.
    Univ Leuven, Belgium; Univ Coll London Hosp, England; IRCCS Osped San Raffaele, Italy.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Lund Univ, Sweden.
    Weyne, Emmanuel
    Univ Leuven, Belgium.
    Hakim, Lukman
    Univ Leuven, Belgium; Airlangga Univ, Indonesia.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, Italy.
    Salonia, Andrea
    IRCCS Osped San Raffaele, Italy.
    Bivalacqua, Trinity J.
    Johns Hopkins Med Inst, MD 21205 USA.
    De Ridder, Dirk
    Univ Leuven, Belgium.
    Milenkovic, Uros
    Univ Leuven, Belgium.
    Ralph, David
    Univ Coll London Hosp, England.
    Garaffa, Giulio
    Univ Coll London Hosp, England.
    Muneer, Asif
    Univ Coll London Hosp, England.
    Joniau, Steven
    Univ Leuven, Belgium.
    Albersen, Maarten
    Univ Leuven, Belgium.
    Intratunical injection of stromal vascular fraction prevents fibrosis in a rat model of Peyronies disease2019In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 124, no 2, p. 342-348Article in journal (Refereed)
    Abstract [en]

    Objective To investigate whether local injection of autologous adipose stromal vascular fraction (SVF) can prevent the development of fibrosis and elastosis in the tunica albuginea (TA) using a rat model of the acute phase of Peyronies disease (PD). Methods A total of 24 male 12-week-old Sprague-Dawley rats were divided into three equal groups: sham; PD without treatment (transforming growth factor-beta [TGF -beta]); and PD treated with SVF 1 day after disease induction. Sham rats received two injections of vehicle into the TA 1 day apart. TGF -beta rats received TGF- beta 1 injection and injection of vehicle 1 day later. SVF rats received TGF-beta 1 injection, followed by SVF 1 day later. One month after treatment, all rats underwent measurement of intracavernosal pressure and mean arterial pressure during electrostimulation of the cavernous nerve. The rats were then killed and penises were harvested for histology and Western blot analysis. Results Erectile function was moderately reduced in the TGF-beta group and was significantly improved after SVF treatment (P amp;lt; 0.05). PD rats developed areas of fibrosis with a significant upregulation of collagen III, collagen I and elastin protein expression. These fibrotic changes were prevented when treated with SVF. Conclusions Local injection of SVF may represent treatment for the acute phase of PD.

  • 15.
    Cazzaniga, Walter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. IRCCS Osped San Raffaele, Unit Urol URI, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Garmo, Hans
    Uppsala Univ Hosp, Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden;Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study2019In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 123, no 3, p. 421-428Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision-making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG-4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s.

    PATIENTS AND METHODS: A propensity score-matched analysis of prostate cancer mortality and all-cause mortality in the SPCG-4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998-2006 was conducted. Cumulative incidence of prostate cancer mortality and all-cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR.

    RESULTS: Matched men in the NPCR treated in 2005-2006 had half the risk of prostate cancer mortality compared to men in the SPCG-4 (HR 0.46, 95% CI 0.19-1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36-1.47).

    CONCLUSIONS: Outcomes after RP for men in the SPCG-4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG-4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.

  • 16.
    Chowdhury, Simon
    et al.
    Kings Coll London, Guys Hosp, Dept Med Oncol, London WC2R 2LS, England.
    Robinson, David
    Thames Canc Registry, London, England.
    Cahill, Declan
    Kings Coll London, Guys Hosp, Dept Urol, London WC2R 2LS, England.
    Rodriguez-Vida, Alejo
    Kings Coll London, Guys Hosp, Dept Med Oncol, London WC2R 2LS, England.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Div Canc Studies, Sect Canc Epidemiol, London, England.
    Møller, Henrik
    Thames Canc Registry, London, England.
    Causes of death in men with prostate cancer: an analysis of 50,000 men from the Thames Cancer Registry.2013In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 112, no 2, p. 182-189Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate causes of death in a UK cohort of patients with prostate cancer.

    PATIENTS AND METHODS: We examined causes of death in a UK cohort of 50,066 men with prostate cancer diagnosed between 1997 and 2006 reported to the Thames Cancer Registry (TCR) and followed-up to the end of 2007. The underlying cause of death was taken from the death certificate. Uptake of PSA screening was low in the UK during the period studied. We examined the relationship between cause of death and patient characteristics at diagnosis including age, cancer stage, and treatment (≤6 months of diagnosis).

    RESULTS: In all, 20,181 deaths occurred during the period; 49.8% recorded as being due to prostate cancer, 17·8% to cardiovascular disease, 11·6% to other cancers, and 20·7% to other causes. Irrespective of age, cancer stage, or treatment ≤6 months of diagnosis, prostate cancer was an important cause of death ranging from 31·6% to 74·3% of all deaths in different subgroups.

    CONCLUSION: For men with prostate cancer diagnosed in a setting where uptake of PSA screening is low, our findings challenge the belief that prostate cancer is not an important cause of death.

  • 17. Crawley, Danielle
    et al.
    Garmo, Hans
    Rudman, Sarah
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala.
    Zethelius, Björn
    Holmberg, Lars
    Adolfsson, Jan
    Van Hemelrijck, Mieke
    Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer2018In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 121, no 2, p. 209-216Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa.

    Subjects and Methods: The Prostate Cancer database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n = 2210) for comparison with data on men with PCa only (n = 23 071). All men had intermediate-(T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20 ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL) localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate logistic regression was used to calculate the odds ratios (ORs) for receipt of curative treatment in men with and without T2DM. Overall survival, for up to 8 years of follow-up, was calculated both for men with T2DM only and for men with T2DM and PCa.

    Results: Men with T2DM were less likely to receive curative treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69-0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and high-risk PCa who did and did not receive curative treatment, respectively.

    Conclusions: Men with T2DM were less likely to receive curative treatment for localized intermediate-and high-risk PCa. Men with T2DM and high-risk PCa who received curative treatment had substantially higher survival times than those who did not. Some of the survival differences represent a selection bias, whereby the healthiest patients received curative treatment. Clinicians should interpret this data carefully and ensure that individual patients with T2DM and PCa are not under-nor overtreated.

  • 18.
    Crawley, Danielle
    et al.
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Garmo, Hans
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Rudman, Sarah
    Guys & St Thomas NHS Fdn Trust, London, England.; Kings Coll Londons, Comprehens Biomed Res Ctr, London, England. .
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Peri Operat Sci Urol & Androl, Umea, Sweden.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Med Prod Agcy, Uppsala, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer.2018In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 121, no 2, p. 209-216Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa.

    SUBJECTS AND METHODS: The Prostate Cancer database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n = 2210) for comparison with data on men with PCa only (n = 23 071). All men had intermediate- (T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20 ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL) localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate logistic regression was used to calculate the odds ratios (ORs) for receipt of curative treatment in men with and without T2DM. Overall survival, for up to 8 years of follow-up, was calculated both for men with T2DM only and for men with T2DM and PCa.

    RESULTS: Men with T2DM were less likely to receive curative treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69-0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and high-risk PCa who did and did not receive curative treatment, respectively.

    CONCLUSIONS: Men with T2DM were less likely to receive curative treatment for localized intermediate- and high-risk PCa. Men with T2DM and high-risk PCa who received curative treatment had substantially higher survival times than those who did not. Some of the survival differences represent a selection bias, whereby the healthiest patients received curative treatment. Clinicians should interpret this data carefully and ensure that individual patients with T2DM and PCa are not under- nor overtreated.

  • 19.
    Danneman, Daniela
    et al.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Drevin, Linda
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Delahunt, Brett
    Univ Otago, Wellington Sch Med & Hlth Sci, Wellington, New Zealand..
    Samaratunga, Hemamali
    Aquesta Pathol, Brisbane, Qld, Australia.;Univ Queensland, Sch Med, Brisbane, Qld, Australia..
    Robinson, David
    Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden..
    Bratt, Ola
    Cambridge Univ Hosp, Dept Urol, Cambridge, England.;Lund Univ, Dept Translat Med, Lund, Sweden..
    Loeb, Stacy
    NYU, Dept Urol & Populat Hlth, New York, NY USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Egevad, Lars
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden..
    Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000-20122017In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 119, no 1, p. 50-56Article in journal (Refereed)
    Abstract [en]

    Objectives To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1-5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9-10) better predict the RP grade. Patients and Methods All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1-2 M0/X prostate cancer on needle biopsy; were aged <= 70 years; had serum PSA concentration of < 20 ng/mL; and underwent a RP < 6 months after diagnosis as their primary treatment. Results Prediction of RP Gleason score increased from 55 to 68% between 2000 and 2012. Most of the increase occurred before 2005 (nine percentage points; P < 0.001); however, when adjusting for Gleason score and year of diagnosis in a multivariable analysis, the prediction of RP Gleason score decreased over time (odds ratio [OR] 0.98; P < 0.002). A change in the ISUP grades would have led to a decreasing agreement between biopsy and RP grades over time, from 68% in 2000 to 57% in 2012, with an OR of 0.95 in multivariable analysis (P < 0.001). Conclusion Agreement between biopsy and RP Gleason score improved from 2000 to 2012, with most of the improvement occurring before the 2005 ISUP grading revision. Had ISUP grades been used instead of Gleason score, the agreement between biopsy and RP grade would have decreased, probably because of its separation of Gleason score 7 into ISUP grades 2 and 3 (Gleason score 3 + 4 vs 4 + 3).

  • 20. Danneman, Daniela
    et al.
    Drevin, Linda
    Delahunt, Brett
    Samaratunga, Hemamali
    Robinson, David
    Bratt, Ola
    Loeb, Stacy
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Egevad, Lars
    Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000-20122017In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 119, no 1, p. 50-56Article in journal (Refereed)
    Abstract [en]

    Objectives To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1-5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9-10) better predict the RP grade. Patients and Methods All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1-2 M0/X prostate cancer on needle biopsy; were aged <= 70 years; had serum PSA concentration of < 20 ng/mL; and underwent a RP < 6 months after diagnosis as their primary treatment. Results Prediction of RP Gleason score increased from 55 to 68% between 2000 and 2012. Most of the increase occurred before 2005 (nine percentage points; P < 0.001); however, when adjusting for Gleason score and year of diagnosis in a multivariable analysis, the prediction of RP Gleason score decreased over time (odds ratio [OR] 0.98; P < 0.002). A change in the ISUP grades would have led to a decreasing agreement between biopsy and RP grades over time, from 68% in 2000 to 57% in 2012, with an OR of 0.95 in multivariable analysis (P < 0.001). Conclusion Agreement between biopsy and RP Gleason score improved from 2000 to 2012, with most of the improvement occurring before the 2005 ISUP grading revision. Had ISUP grades been used instead of Gleason score, the agreement between biopsy and RP grade would have decreased, probably because of its separation of Gleason score 7 into ISUP grades 2 and 3 (Gleason score 3 + 4 vs 4 + 3).

  • 21. Danneman, Daniela
    et al.
    Drevin, Linda
    Robinson, David
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Egevad, Lars
    Gleason inflation 1998-2011: a registry study of 97 168 men2015In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 115, no 2, p. 248-255Article in journal (Refereed)
    Abstract [en]

    Objectives: To study long-term trends in Gleason grading in a nationwide population and to assess the impact of the International Society of Urological Pathology (ISUP) revision in 2005 of the Gleason system on grading practices, as in recent years there has been a shift upwards in Gleason grading of prostate cancer. Patients and Methods: All newly diagnosed prostate cancers in Sweden are reported to the National Prostate Cancer Register (NPCR). In 97 168 men with a primary diagnosis of prostate cancer on needle biopsy from 1998 to 2011, Gleason score, clinical T stage (cT) and serum levels of prostate-specific antigen (s-PSA) at diagnosis were analysed. Results: Gleason score, cT stage and s-PSA were reported to the NPCR in 97%, 99% and 99% of cases. Before and after 2005, Gleason score 7-10 was diagnosed in 52% and 57%, respectively (P < 0.001). After standardisation for cT stage and s-PSA with 1998 as baseline these tumours increased from 59% to 72%. Among low-risk tumours (stage cT1 and s-PSA 4-10 ng/mL) Gleason score 7-10 increased from 16% in 1998 to 40% in 2011 (P trend < 0.001), mean 19% and 33% before and after 2005 (P < 0.001). Among high-risk tumours (stage T3 and s-PSA 20-50 ng/mL) Gleason score 7-10 increased from 65% in 1998 to 94% in 2011 (P trend < 0.001), mean 78% and 90% before and after 2005 (P < 0.001). A Gleason score of 2-5 was reported in 27% in 1998 and 1% in 2011. Gleason score 5 decreased sharply after 2005 and Gleason score 2-4 was almost abandoned. Conclusions: There has been a gradual shift towards higher Gleason grading, which started before 2005 but became more evident after the ISUP 2005 revision. Among low-stage tumours reporting of Gleason score 7-10 was more than doubled during the study period. When corrected for stage migration upgrading is considerable over recent decades. This has clinical consequences for therapy decisions such as eligibility for active surveillance. Grading systems need to be as stable as possible to enable comparisons over time and to facilitate the interpretation of the prognostic impact of grade.

  • 22. Danneman, Daniela
    et al.
    Drevin, Linda
    Robinson, David
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Egevad, Lars
    Gleason inflation 1998-2011: a registry study of 97,168 men2015In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 115, no 2, p. 248-55Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To study long-term trends in Gleason grading in a nationwide population and to assess the impact of the International Society of Urological Pathology (ISUP) revision in 2005 of the Gleason system on grading practices, as in recent years there has been a shift upwards in Gleason grading of prostate cancer.

    PATIENTS AND METHODS: All newly diagnosed prostate cancers in Sweden are reported to the National Prostate Cancer Register (NPCR). In 97 168 men with a primary diagnosis of prostate cancer on needle biopsy from 1998 to 2011, Gleason score, clinical T stage (cT) and serum levels of prostate-specific antigen (s-PSA) at diagnosis were analysed.

    RESULTS: Gleason score, cT stage and s-PSA were reported to the NPCR in 97%, 99% and 99% of cases. Before and after 2005, Gleason score 7-10 was diagnosed in 52% and 57%, respectively (P < 0.001). After standardisation for cT stage and s-PSA with 1998 as baseline these tumours increased from 59% to 72%. Among low-risk tumours (stage cT1 and s-PSA 4-10 ng/mL) Gleason score 7-10 increased from 16% in 1998 to 40% in 2011 (P trend < 0.001), mean 19% and 33% before and after 2005 (P < 0.001). Among high-risk tumours (stage T3 and s-PSA 20-50 ng/mL) Gleason score 7-10 increased from 65% in 1998 to 94% in 2011 (P trend < 0.001), mean 78% and 90% before and after 2005 (P < 0.001). A Gleason score of 2-5 was reported in 27% in 1998 and 1% in 2011. Gleason score 5 decreased sharply after 2005 and Gleason score 2-4 was almost abandoned.

    CONCLUSIONS: There has been a gradual shift towards higher Gleason grading, which started before 2005 but became more evident after the ISUP 2005 revision. Among low-stage tumours reporting of Gleason score 7-10 was more than doubled during the study period. When corrected for stage migration upgrading is considerable over recent decades. This has clinical consequences for therapy decisions such as eligibility for active surveillance. Grading systems need to be as stable as possible to enable comparisons over time and to facilitate the interpretation of the prognostic impact of grade.

  • 23. Daouacher, Georgios
    et al.
    von Below, Catrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Gestblom, Charlotta
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Grzegorek, Rafael
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Waldén, Mauritz
    Laparoscopic extended pelvic lymph node (LN) dissection as validation of the performance of [(11) C]-acetate positron emission tomography/computer tomography in the detection of LN metastasis in intermediate- and high-risk prostate cancer2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 1, p. 77-83Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the accuracy of the radiopharmaceutical [(11) C]-acetate combined with positron emission tomography/computer tomography (acetate-PET/CT) in lymph node (LN) staging in newly diagnosed prostate cancer cases. A second aim was to evaluate the potential discriminative properties of acetate-PET/CT in clinical routine.

    PATIENTS AND METHODS: In a prospective comparative study, from July 2010 to June 2013, 53 men with newly histologically diagnosed intermediate- or high-risk prostate cancer underwent acetate-PET/CT investigation at one regional centre before laparoscopic extended pelvic LN dissection (ePLND) at one referral centre. The sensitivity, specificity and accuracy of acetate-PET/CT were calculated. Comparisons were made between true-positive and false-negative PET/CT cases to identify differences in the clinical parameters: PSA level, Gleason status, lymph metastasis burden and size, calculated risk of LN involvement, and curative treatment decisions.

    RESULTS: In all, 26 patients had surgically/histologically confirmed LN metastasis (LN+). Acetate-PET/CT was true positive in 10 patients, false positive in one, false negative in 16, and true negative in 26. The individual sensitivity was 38%, specificity 96%, and accuracy 68%. The acetate-PET/CT positive cases had significantly more involved LNs (mean 7.9 vs 2.4, P < 0.001) with larger cancer diameters (14.1 vs 4.9 mm, P = 0.001) and fewer eventually had treatment with curative intent (40% vs 94%, P <0.005), although we lack long-term outcome data.

    CONCLUSION: Acetate-PET/CT has too low a sensitivity for routine LN staging but the specificity is high. The acetate-PET/CT positive cases have a very high burden of LN spread.

  • 24.
    Ebbinge, Maria
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Berglund, Anders
    EpiStat, Sweden.
    Varenhorst, Eberhard
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Hedlund, Per Olov
    Karolinska Inst, Sweden.
    Sandblom, Gabriel
    Soder Sjukhuset, Sweden.
    Clinical and prognostic significance of changes in haemoglobin concentration during 1 year of androgen-deprivation therapy for hormone-naive bone-metastatic prostate cancer2018In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 122, no 4, p. 583-591Article in journal (Refereed)
    Abstract [en]

    Objective To estimate the strength of change in haemoglobin (Hb) concentrations during 1 year of androgen-deprivation therapy (ADT) as a predictor of survival in hormone-naive patients with bone-metastatic (Stage M1b) prostate cancer. Patients and Methods The patients included in this study were taken from the randomised trial (number 5) carried out by the Scandinavian Prostate Cancer Group (SPCG), comparing parenteral oestrogen with total androgen blockade (TAB) in hormone-naive M1b prostate cancer. We identified 597 men where Hb measurements were made at enrolment, as well as at 3, 6 and 12 months of ADT. The time-dependent impact of Hb concentration changes on overall survival (OS) was analysed using multivariate Cox proportional hazards analysis. The 10-year OS according to increase/decrease in Hb concentration for the three treatment periods was demonstrated using Kaplan-Meier curves. Results Multivariate analysis of changes in Hb concentration between baseline and 3 months showed better survival in patients with a decrease in Hb concentration (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.11-1.80) compared to those with an increase, whilst there was no difference in survival associated with a change in Hb concentration between 3 and 6 months (HR 0.93, 95% CI 0.76-1.12). Contrary to the first 3 months, poorer survival was seen in patients with a decrease in Hb concentration between 6 and 12 months (HR 0.76, 95% CI 0.62-0.92) compared to those with an increase. Conclusions In a large cohort of Scandinavian men with hormone-nave M1b prostate cancer, an increase in Hb concentration between baseline and 3 months of ADT was associated with significantly poorer survival, whereas an increase between 6 and 12 months was associated with better survival. These findings provide new information about patterns of change in Hb concentrations during 12 months of ADT for M1b prostate cancer, and survival. Clinicians should be aware of the prognostic value of Hb concentration changes during ADT in M1b prostate cancer.

  • 25.
    Englund, Gunnar
    KTH, Superseded Departments, Mathematics.
    Optimizing the therapeutic approach of transurethral alprostadil2000In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 86, no 1, p. 68-74Article in journal (Refereed)
    Abstract [en]

    Objective To investigate the efficacy and safety of two different starting doses of transurethral alprostadil (250 mu g and 500 mu g, MUSE(R), Vivus Inc., Menlo Park, CA, USA, and Astra Lakemedel AB, Sodertalje, Sweden) and the need for dose titration in a general population with erectile dysfunction. Patients and methods In a 12-week randomized and open multicentre study with parallel groups, 166 patients were randomised to a starting dose of either 250 or 500 mu g of MUSE and evaluated for safety. Of these patients, 142 were included in the analysis of efficacy. MUSE marked in four doses (125, 250, 500 and 1000 mu g) was supplied and during the trial the dose could be increased or decreased step-wise until a satisfactory response was attained. The efficacy was assessed using the Erection Assessment Scale (EAS), as coitus (by diary) and the International Index of Erectile Function. Results The lowest dose of MUSE with which the patients achieved at least one EAS score of 4 or 5 was 125 mu g for 1% of participants, 250 mu g for 27%, 500 mu g for 32%. 1000 mu g for 6%, and finally 1000 mu g plus a pubic band for 8%. Thirty-five of the 142 patients (25%) did not report an EAS of 4 or 5. Most patients ( > 60%) achieved an EAS of 4 or 5 on the lower doses (125, 250 and 500 mu g). Almost all patients who had an EAS score of 4 or 5 also had intercourse. In all, 68% reported sexual intercourse at least once in course of the study. More patients reported penile pain while treated with 500 mu g than with 250 mu g (P < 0.05) during the first 4 weeks, However, the penile pain was severe in very few men and it was a minor problem. Hypotensive symptoms were reported six times, independently of dose level. The administration of MUSE was generally rated as comfortable. No patients reported urethral stricture, penile fibrosis, or priapism either in the clinic or at home. Conclusion Recommending 500 mu g as a starting dose increased the percentage of patients reporting at least one EAS of 4-5, with or without sexual intercourse, from 28% to 60%. No serious dose-related systemic effects were seen. When starting on 500 mu g, patients were more likely to find directly the dose that gave sufficient response and treatment satisfaction. We suggest that the appropriate starting dose of MUSE should be 500 mu g.

  • 26.
    Fagerström, Tim
    et al.
    Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
    Nyman, Claes R.
    Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
    Hahn, Robert G.
    Clinical Research Centre, Södertälje Hospital, Sweden.
    Bipolar transurethral resection of the prostate causes less bleeding than the monopolar technique: a single-centre randomized trial of 202 patients2010In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 105, no 11, p. 1560-1564Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare bipolar with the conventional monopolar transurethral resection of the prostate (TURP) for blood loss and speed of resection.

    PATIENTS AND METHODS: In all, 202 consecutive patients from the hospital waiting list were randomized to undergo TURP using either a bipolar system (Surgmaster TURis, Olympus, Tokyo, Japan) or a monopolar system (24 F, Storz, Tübingen, Germany). The blood loss during and after surgery was measured using a photometer. Other variables compared included indices of resection speed and transfusion rate.

    RESULTS: There were no statistically significant differences in operative duration, resection weight, resection speed or radicality of resection. However, the median blood loss was 235 mL for the bipolar and 350 mL for monopolar TURP (P < 0.001). The decrease in blood haemoglobin concentration during the day of surgery was smaller in the bipolar group (5.5% vs 9.6%P < 0.001). Fewer patients were transfused with erythrocytes (4% vs 11%, P < 0.01), which can be explained by the much lower 75th percentile for blood loss in the bipolar group (at 472 vs 855 mL, respectively).

    CONCLUSIONS: Bipolar TURP using the TURis system was performed with the same speed as monopolar TURP but caused 34% less bleeding, the difference being greatest (81%) for the largest blood losses. Bipolar TURP also required fewer erythrocyte transfusions than the conventional monopolar technique.

  • 27.
    Gardmark, T.
    et al.
    Gårdmark, T., Department of Urology, Surgical Sciences, Uppsala, Sweden.
    Jahnson, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Wahlquist, R.
    Department of Urology, Surgical Sciences, Oslo, Norway.
    Wijkstrom, H.
    Wijkström, H., Department of Urology, Surgical Sciences, Stockholm, Sweden.
    Malmstrom, P.-U.
    Malmström, P.-U., Department of Urology, Surgical Sciences, Uppsala, Sweden.
    Analysis of progression and survival after 10 years of a randomized prospective study comparing mitomycin-C and bacillus Calmette-Guérin in patients with high-risk bladder cancer2007In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 99, no 4, p. 817-820Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To report the 10-year follow-up of a study randomizing between instillations of bacillus Calmette-Guérin (BCG) and mitomycin-C (MMC) for treating high-risk and not muscle-invasive urinary bladder cancer to assess progression, the need for more aggressive treatment and survival (cancer-specific and overall), as many of the published studies comparing different treatments for disease that is not muscle-invasive have a short follow-up. PATIENTS AND METHODS: Between 1987 and 1992, 261 patients were included, they had frequently recurring Ta/T1G1-G2, T1G3 or primary Tis-dysplasia. The patients were randomized to treatment with either 40 mg of MMC or 120 mg of BCG (Danish strain 1331) given weekly for 6 weeks, then monthly up to a year and finally every third month for a further year. The 250 evaluable patients were followed using hospital files and national registers on causes of death. RESULTS: The median follow-up for survivors was 123 months. The disease progressed in 58 (23%) of the patients, 34 in the MMC group and 24 in the BCG group (P = 0.26). Of the 140 patients who died, 68 were in the BCG and 72 in the MMC group (log-rank P = 0.98), most (95, 68%) died from other causes. CONCLUSION: Based on the follow-up of the present patients it cannot be concluded that the drugs originally administered, MMC or BCG, differed in their effect on progression, need for subsequent treatment or survival. © 2007 The Authors.

  • 28.
    Gladh, Gunilla
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Mattsson, Sven
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Lindström, Sivert
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Anogenital electrical stimulation as treatment of urge incontinence in children2001In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 87, no 4, p. 366-371Article in journal (Refereed)
    Abstract [en]

    Objectives To evaluate retrospectively the result of anogenital afferent stimulation (AGAS) in neurological healthy children with therapy-resistant urge incontinence.

    Patients and method The study included 48 children (24 girls and 24 boys, 5–14 years old) with a diagnosis of bladder instability verified by cystometry in all. Anogenital afferent stimulations were applied using a battery-powered dual constant-current stimulator. The children were stimulated continuously at 10 Hz for 20 min once or twice daily and if required the children and/or the parents continued to apply the treatment at home. For home stimulation a single (anal) channel stimulator was used. The patients were instructed to stimulate for 20 min at maximum intensity two to three times a week until the effects were optimal. The outcome was evaluated retrospectively by comparing voiding/incontinence diaries obtained before and at the follow-up 6–12 months after the end of treatment.

    Results AGAS was applied at the clinic for a median (range) of 9 (4–20) times. Thirty-one children continued with home stimulation for another 25 (5–96) sessions. At the follow-up, 18 children were cured and another seven improved, with a leakage score of less than half that before treatment. The treatment was well tolerated by most children.

    Conclusions Anogenital afferent stimulation is an effective, potentially curative treatment in children with severe urge incontinence. Home stimulation is a well accepted adjuvant to treatment at the clinic and improves the outcome.

  • 29. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    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-Guérin2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 1, p. 44-52Article in journal (Refereed)
    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.

  • 30.
    Gudjonsson, Sigurdur
    et al.
    Skåne University Hospital, Sweden .
    Blackberg, Mats
    Helsingborg County Hospital, Sweden .
    Chebil, Gunilla
    Helsingborg County Hospital, Sweden .
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Olsson, Hans
    Lund University, Sweden .
    Bendahl, Par-Ola
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Mansson, Wiking
    Skåne University Hospital, Sweden .
    Liedberg, Fredrik
    Skåne University Hospital, Sweden Vaxjo County Hospital, Sweden .
    The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS)2012In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 110, no 2B, p. E41-E45Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. PATIENTS AND METHODS Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. RESULTS The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (greater than= 2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder mucosa showed sensitivity and specificity of 46% and 89%, respectively. CONCLUSION Traditional cold-cup biopsies are unreliable for detecting CIS in bladder mucosa and negative findings must be interpreted with caution.

  • 31. Gustavsson, Heléne
    et al.
    Wang, Wanzhong
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jennbacken, Karin
    Welén, Karin
    Damber, Jan-Erik
    ADAMTS1, a putative anti-angiogenic factor, is decreased in human prostate cancer2009In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 104, no 11, p. 1786-1790Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the expression of 'ADAM metallopeptidase with thrombospondin type I motif, 1' (ADAMTS1) in human prostate cancer, and to study its relationship to microvessel density (MVD) and metastasis. ADAMTS1 has been described as an anti-angiogenic and antitumour factor, but its function in prostate cancer is unknown. PATIENTS AND METHODS: ADAMTS1 expression was evaluated by immunohistochemistry in specimens obtained by transurethral resection of the prostate from patients with hormone-naïve and hormone-refractory prostate tumours, including adjacent benign tissue. A semiquantitative scoring system was used for evaluating the staining. MVD was quantified by counting the number of CD34-positive blood vessels. RESULTS: ADAMTS1 was strongly expressed in the luminal epithelial cells in benign prostate glands, whereas expression was significantly lower in prostate cancer cells. There was no obvious difference between hormone-naïve and hormone-refractory tumours, and ADAMTS1 expression did not correlate with Gleason score. However, in hormone-refractory tumours from patients with metastatic disease, the expression of ADAMTS1 was significantly lower than in tumours from patients without metastases. Furthermore, the MVD was higher in hormone-refractory than in hormone-naïve tumours and benign tissue, and MVD correlated with Gleason score. There was no association between ADAMTS1 and MVD in the hormone-naïve tumours, while hormone-refractory tumours with low ADAMTS1 expression had a higher MVD than those with moderate/high expression. CONCLUSION: ADAMTS1 expression is decreased in prostate cancer, and might be involved in the early steps of prostate cancer development. Further, ADAMTS1 might have an anti-angiogenic and antimetastatic role in hormone-refractory prostate cancer, where low ADAMTS1 expression is associated with a high MVD and metastasis.

  • 32.
    Gårdmark, Truls
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Jahnson, Staffan
    Wahlquist, Rolf
    Wijkström, Hans
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Analysis of progression and survival after 10 years of a randomized prospective study comparing mitomycin-C and bacillus Calmette-Guérin in patients with high-risk bladder cancer2007In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 99, no 4, p. 817-820Article in journal (Refereed)
    Abstract [en]

    Objective: To report the 10-year follow-up of a study randomizing between instillations of bacillus Calmette-Guérin (BCG) and mitomycin-C (MMC) for treating high-risk and not muscle-invasive urinary bladder cancer to assess progression, the need for more aggressive treatment and survival (cancer-specific and overall), as many of the published studies comparing different treatments for disease that is not muscle-invasive have a short follow-up.

    Patients and methods: Between 1987 and 1992, 261 patients were included; they had frequently recurring Ta/T1G1–G2, T1G3 or primary Tis-dysplasia. The patients were randomized to treatment with either 40 mg of MMC or 120 mg of BCG (Danish strain 1331) given weekly for 6 weeks, then monthly up to a year and finally every third month for a further year. The 250 evaluable patients were followed using hospital files and national registers on causes of death.

    Results: The median follow-up for survivors was 123 months. The disease progressed in 58 (23%) of the patients, 34 in the MMC group and 24 in the BCG group (P = 0.26). Of the 140 patients who died, 68 were in the BCG and 72 in the MMC group (log-rank P = 0.98); most (95, 68%) died from other causes.

    Conclusion: Based on the follow-up of the present patients it cannot be concluded that the drugs originally administered, MMC or BCG, differed in their effect on progression, need for subsequent treatment or survival.

  • 33.
    Gårdmark, Truls
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wester, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    De la Torre, Manuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastases2005In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 95, no 7, p. 982-986Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the expression of HER2 receptors (previously reported to be over-expressed in malignant urothelium) in both primary tumours and metastases of transitional cell cancer, using two different staining methods and two different scoring techniques, considering the potential use of these receptors as targets for planned systemic anti-HER2 nuclide-based treatment. MATERIALS AND METHODS: HER2 expression was evaluated with two different immunohistochemical methods in 90 patients with primary urinary bladder cancer tumours and corresponding metastases. Sections were first stained with the commercially available breast cancer test kit (HercepTest, Dako, Glostrup, Denmark). Parallel sections were then stained with a modified HercepTest procedure. Two different evaluation criteria were compared; the HercepTest score that requires > or = 10% stained tumour cells (as for breast cancer) and a proposed 'Target score' that requires > 67% stained tumour cells. The latter score is assumed to be preferable for HER2-targeted radionuclide therapy. RESULTS: Using the HercepTest kit, the Target score gave lower fractions of positive primary tumours and metastases than the HercepTest score. The modified HercepTest staining procedure and Target score gave high HER2 values in 80% of primary tumours and 62% of metastases, which is considerably more than that obtained with the HercepTest staining and score. There was a significant decrease in HER2 positivity with increasing distance from the primary tumour. In nine sentinel-node metastases assessed, all but one were HER2-positive. Considering all regional metastases, 74% were positive, and of distant metastases, 47%; 72% of the patients with positive primary tumours also expressed HER2 in their metastases. CONCLUSIONS: When combining the modified HercepTest with customised evaluation criteria, more HER2-positive tumours were diagnosed. The degree of HER2 down-regulation was significantly higher in distant than in regional metastases. HER2-targeted therapy may be an alternative or complementary to other methods in the future treatment of metastatic urinary bladder carcinoma.

  • 34.
    Hahn, Robert G.
    et al.
    South Hospital, Stockholm, Sweden.
    Fagerström, Tim
    South Hospital, Stockholm, Sweden.
    Tammela, Teuvo L. J.
    Tampere University Hospital, Finland.
    Van Vierssen Trip, Oncko
    Ziekenhuis Gelderse Vallei, Ede, the Netherlands.
    Beisland, Hans Olav
    Sorlandet Hospital, Arendal, Norway.
    Duggan, Annette
    GlaxoSmithKline, Greenford, UK.
    Morrill, Betsy
    GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
    Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride2007In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 99, no 3, p. 587-594Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine whether pretreatment with dutasteride, a dual 5alpha-reductase inhibitor (5ARI), reduces surgical blood loss or postoperative complications in patients with benign prostatic hyperplasia (BPH) who undergo transurethral resection of the prostate (TURP).

    PATIENTS AND METHODS: This double-blind, randomized, placebo-controlled, multicentre study comprised 214 patients with BPH. Placebo was compared with dutasteride 0.5 mg/day 2 weeks before and after TURP, or 4 weeks before and 2 weeks after TURP. Surgical blood loss was measured using a haemoglobin photometer (HemoCue AB, Angelholm, Sweden) and postoperative adverse events were recorded. Microvessel density (MVD) was calculated by immunostaining and light microscopy of the prostatic chips.

    RESULTS: Although dutasteride reduced serum dihydrotestosterone (DHT) by 86-89% in 2-4 weeks, and intraprostatic DHT was approximately 10 times lower than in the placebo group, the (adjusted) mean haemoglobin (Hb) loss during surgery was 2.15-2.55 g Hb/g resectate with no significant difference in blood loss between the groups either during or after TURP. Clot retention occurred in 6-11% and urinary incontinence in 14-15% of patients during the 14 weeks after TURP, with no difference between the groups. The MVD at TURP was also similar for all groups.

    CONCLUSION: There were no significant reductions in blood loss during or after TURP or complications afterward with dutasteride compared with placebo, despite significant suppression of intraprostatic DHT. Blood loss and transfusion rates in the placebo group were lower than those previously reported in studies where there was a beneficial effect of a 5ARI, relative to placebo, on bleeding during TURP.

  • 35.
    Hennenberg, Martin
    et al.
    Department of Urology, University of Munich, Munich, Germany.
    Strittmatter, Frank
    Department of Urology, University of Munich, Munich, Germany.
    Walther, Sebastian
    Department of Urology, University of Munich, Munich, Germany.
    Hedlund, Petter
    Urological Research Institute, University of San Raffaele, Milan, Italy.
    Andersson, Karl-Erik
    Wake Forest Institute for Regenerative Medicine, Wake Forst University School of Medicine, Winston-Salem, NC, USA.
    Stief, Christian G
    Department of Urology, University of Munich, Munich, Germany.
    Schlenker, Boris
    Department of Urology, University of Munich, Munich, Germany.
    Gratzke, Christian
    Department of Urology, University of Munich, Munich, Germany.
    α1-adrenoceptor activation induces phosphorylation of β2-adrenoceptors in human prostate tissue2011In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 108, no 6, p. 922-928Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    • To test whether β1-adrenoceptor activation leads to phosphorylation of the β2-adrenoceptor in human prostate tissue.

    PATIENTS AND METHODS:

    • Prostate tissue from patients undergoing radical prostatectomy was stimulated in vitro with the α1-adrenergic agonist phenylephrine (10 µM).

    • α2-adrenoceptor phosphorylation at serines 345/346 was studied using Western blot analysis with a phospho-specific antibody.

    • The role of second messenger kinases was assessed by studying the effects of the protein kinase C (PKC) inhibitor Ro 31-8425 and the protein kinase A (PKA) inhibitor H89 on phenylephrine-induced phosphorylation.

    • The expression of G protein-coupled receptor kinases (GRKs) 2/3 was analysed using quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry.

    RESULTS:

    • Stimulation of prostate tissue with phenylephrine resulted in phosphorylation of the β2-adrenoceptor (5, 10 and 20 min after stimulation).

    • This α1-adrenoceptor-induced phosphorylation of β2-adrenoceptors was resistant to inhibition of PKC and PKA.

    • Changes in phosphorylation levels were not attributable to changes in receptor levels, as these remained constant during stimulation.

    • RT-PCR and Western blot analysis showed expression of GRK2/3 in human prostate tissues.

    • Immunohistochemical staining showed that GRK2/3 expression in human prostate tissue is located to stromal and smooth muscle cells.

    CONCLUSIONS:

    • Activation of α1-adrenoceptors causes phosphorylation of β2-adrenoceptors in the human prostate. This may enhance α1-adrenergic contraction and is possibly mediated by GRK2, which is expressed in prostate smooth muscle.

    • Mutual regulation between different adrenergic receptors might be involved in the therapeutic effects of α1-blockers in patients with benign prostate hyperplasia.

  • 36. Henningsohn, L
    et al.
    Wijkström, H
    Pedersen, J
    Ahlstrand, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Urology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Aus, G
    Bergmark, K
    Onelöv, E
    Steineck, G
    Time after surgery, symptoms and well-being in survivors of urinary bladder cancer2003In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 91, no 4, p. 325-330Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate how an increasing burden of symptoms influences well-being, anxiety and depression at different intervals after a radical cystectomy with urostomy for bladder cancer, as this therapy can induce long-term distressful symptoms. PATIENTS AND METHODS: Patients with bladder cancer undergoing radical cystectomy in Stockholm between 1969 and 1995 were matched with 434 controls from the normal population, all 404 patients operated on between 1985 and 1995 at three other hospitals in Sweden were invited to enter the study. The final analysis included 306 patients and 310 controls, all assessed for symptoms and well-being. RESULTS: A low or moderate level of well-being was reported by 35% of the patients having none or one of the symptoms studied, by 39% with two symptoms, by 45% with three symptoms and by 66% of those with four or more symptoms. The values, irrespective of symptom burden, were 45% after 2-5 years of follow-up, 58% after 6-10 years and 38% at > 10 years after surgery. The total symptom burden also influenced the risk of anxiety and depression. Symptom prevalence remained largely unaffected by the duration of follow-up, except for defecation urgency. CONCLUSIONS: The number of long-term symptoms after radical surgery with a urostomy for urinary bladder cancer affects the risk of anxiety, depression and low or moderate well-being.

  • 37.
    Häggström, Christel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.;Umea Univ, Dept Biobank Res, S-90185 Umea, Sweden..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. 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 cancer2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 6, p. 850-852Article in journal (Other academic)
  • 38.
    Häggström, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Clinical Sciences, Diabetes and Cardiovascular Diseases, Genetic Epidemiology, Lund University, Lund, Sweden.
    Garmo, Hans
    Holmberg, Lars
    Van Hemelrijck, Mieke
    Interpretation of conventional survival analysis and competing-risk analysis: an example of hypertension and prostate cancer2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 6, p. 850-852Article in journal (Refereed)
  • 39.
    Häggström, S
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Stattin, P
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Wikström, P
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bergh, A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Damber, J E
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Castration-induced reduction of vascular endothelial growth factor expression in benign human prostate tissue is lost in advanced prostate cancer.2001In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 88, no 1, p. 110-6Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine the role of vascular response in the castration-induced regression of benign and malignant human prostate tissue, as recent studies show that castration rapidly decreases blood flow and induces endothelial cell death, which may be important for subsequent epithelial cell death and involution of the glandular tissue of the prostate.

    MATERIALS AND METHODS: The expression of vascular endothelial growth factor (VEGF) and its receptors was analysed using the quantitative reverse transcriptase-polymerase chain reaction, in benign and tumour areas of core biopsies taken before, and approximately 1 week after castration therapy. The castration-induced VEGF response was related to therapy-induced changes in tumour cell apoptotic index and subsequent response in serum prostate-specific antigen (PSA). In another set of patients, serum VEGF was quantified by enzyme-linked immunosorbent assay before, and at 3--6 months after castration therapy.

    RESULTS: VEGF mRNA was down-regulated after castration in benign prostate tissue (P < or = 0.05), whereas in tumour tissue, VEGF levels were reduced in some of the patients but unchanged or increased in others. In most patients whose tumour tissue responded with VEGF reduction, there was a corresponding increase in tumour cell apoptosis. Serum VEGF levels were not significantly changed after castration. Almost all patients responded with a substantial reduction in serum PSA after castration.

    CONCLUSION: Castration reduces VEGF mRNA expression in benign prostate tissue and generally in those prostate tumours where castration also induces tumour cell apoptosis. This suggests that a therapy-induced down-regulation of VEGF could be important for tumour cell death.

  • 40.
    Jacobsen, Jan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Landberg, G
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Expression of vascular endothelial growth factor protein in human renal cell carcinoma2004In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 93, no 3, p. 297-302Article in journal (Refereed)
  • 41.
    Jacobsen, Jan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Different isoform patterns for vascular endothelial growth factor between clear cell and papillary renal cell carcinoma.2006In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 97, no 5, p. 1102-1108Article in journal (Refereed)
  • 42.
    Jahnson, Staffan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Science & Engineering. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Modulation of the inflammatory response after sclerotherapy for hydrocoele/spermatocoele2019In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 123, no 5A, p. E63-E68Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate the modulation of the inflammatory response after sclerotherapy for hydrocoele/spermatocoele.

    Patients and Methods

    All patients with hydrocoele or spermatocoele presenting at the Department of Urology, University Hospital, Linköping, Sweden, from 2006 to 2012, were included in this prospective observational study of sclerotherapy for hydrocoele/spermatocoele using polidocanol as a sclerosing agent and adjuvant antibiotic and anti‐inflammatory medication (AAAM) for modulation of the inflammatory response. Patients were clinically evaluated within 24–48 h after a complication or adverse event possibly related to sclerotherapy. Evaluation of cure was scheduled after 3 months and re‐treatment, if necessary was carried out in the same manner as the first treatment. Groups of patients were compared using the chi‐squared test and logistic regression analysis.

    Results

    From a total of 191 patients, AAAM was given to 126, of whom 5% had subclinical epididymitis/swelling (SES) compared to 26% of the patients without AAAM (P < 0.001). No other complication was observed. The rate of cure for the whole group of patients was 93% after one or two treatments and significantly higher in the group with AAAM than in the group without AAAM (96% vs 88%, P = 0.03).

    Conclusions

    Modulation of the inflammatory response after sclerotherapy resulted in a lower incidence of SES and an increased cure rate.

  • 43.
    Johansson, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Rudolfsson, Stina Häggström
    Kilter, Sigrid
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Targeting castration-induced tumour hypoxia enhances the acute effects of castration therapy in a rat prostate cancer model2011In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 107, no 11, p. 1818-1824Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: •  To explore the effects of castration therapy, the standard treatment for advanced prostate cancer, in relation to tumour hypoxia and to elicit its importance for the short- and long-term therapeutic response.

    MATERIAL AND METHODS: •  We used the androgen-sensitive rat Dunning H prostate tumour model that transiently responds to castration treatment followed by a subsequent relapse, much like the scenario in human patients. •  Tumour tissues were analysed using stereological methods in intact, 1 and 7 days after castration therapy.

    RESULTS: •  Hypoxia was transiently up-regulated after castration therapy and correlated with the induction of tumour cell apoptosis. •  When castration therapy was combined with tirapazamine (TPZ), a drug that targets hypoxic cells and the vasculature, the effects on tumour cell apoptosis and tumour volume were enhanced in comparison to either castration or TPZ alone.

    CONCLUSION: •  The present study suggests that castration-induced tumour hypoxia is a novel target for therapy.

  • 44.
    Kirrander, Peter
    et al.
    Örebro University Hospital.
    Andrén, Ove
    Örebro University Hospital.
    Windahl, Torgny
    Örebro University Hospital. Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Dynamic sentinel node biopsy in penile cancer: initial experiences at a Swedish referral centre2013In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 111, no 3B, p. E48-E53Article in journal (Refereed)
    Abstract [en]

    Study Type Therapy (case series) Level of Evidence4 What's known on the subject? and What does the study add? According to the current European Association of Urology Guidelines, dynamic sentinel node biopsy is the recommended approach to assess lymph node status in men with cN0 intermediate and high risk penile cancer. Nevertheless, most encouraging results derive from a limited number of studies. The present study shows a false-negative rate of 15%, comparable with or better than several previous studies. Nevertheless, the aim should be a false-negative rate of no more than 5%. We conclude that increased overall experience and the use of the complete modern dynamic sentinel node biopsy protocol are paramount to improve results.

    OBJECTIVE center dot To evaluate the false-negative rate and complication rate of dynamic sentinel node biopsy (DSNB) in penile cancer.

    PATIENTS AND METHODS center dot In this retrospective study, 58 unilaterally or bilaterally clinically lymph node negative (cN0) patients with penile cancer (57 squamous cell carcinomas and one malignant melanoma), scheduled for DSNB at the orebro University Hospital, Sweden, between 1999 and 2011, were analysed. center dot Preoperative ultrasonography and fine-needle aspiration cytology of suspicious nodes were not introduced until 2008. center dot Patients were assessed by lymphoscintigraphy using 99mtechnetium nanocolloid on the day before surgery and the dissection of sentinel nodes was aided by the lymphoscintigraphic images and intraoperative detection of radiotracer and patent blue dye. center dot The false-negative rate and complication rate were calculated per groin.

    RESULTS center dot Of the 58 patients, 32 (55%) underwent preoperative ultrasonography. center dot Two patients had positive fine-needle aspiration cytology and discontinued further DSNB protocol. Of the remaining 56 patients, all but one were bilaterally cN0 and hence 111 cN0 groins were assessed by lymphoscintigraphy. center dot In the 55 bilaterally cN0 patients, lymphoscintigraphy visualized a bilateral sentinel node in 34 (62%). center dot At surgery, all excised sentinel nodes were radioactive while 43% were additionally blue. In total, at least one sentinel node was harvested in 96 (86%) of the DSNB staged groins. center dot A positive sentinel node was found in 11 groins (bilaterally in three patients). During a median follow-up of 21 months, two false-negative cases emerged, producing a false-negative rate of 15%. Both false-negative cases occurred during the first half of the study. The complication rate was 10%. The majority of complications were minor and transient.

    CONCLUSIONS center dot DSNB is a minimally invasive staging tool in men with cN0 penile cancer, enabling early detection of metastatic disease and thus optimal care. center dot Our false-negative rate of 15% is comparable or even favourable in comparison with several previous studies, but far from the 5% or less that we aim for. The complication rate found is somewhat higher than previously reported. center dot With increased overall experience and the continued use of the complete DSNB protocol, we believe our results will improve and the complication rate will decrease.

  • 45. Kirrander, Peter
    et al.
    Kolaric, Aleksandra
    Helenius, Gisela
    Windahl, Torgny
    Andrén, Ove
    Stark, Jennifer Rider
    Lillsunde-Larsson, Gabriella
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Karlsson, Mats
    Human papillomavirus prevalence, distribution and correlation to histopathological parameters in a large Swedish cohort of men with penile carcinoma2011In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 108, no 3, p. 355-359Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To analyse the overall and type-specific human papillomavirus (HPV) prevalence and distribution in penile carcinoma and determine the correlation to histopathological parameters.

    PATIENTS AND METHODS: In this retrospective study, we analysed HPV status in 241 patients with penile carcinoma, treated at Örebro University Hospital, Örebro, Sweden, between 1984 and 2008. Age and date at diagnosis was recorded. The tumour specimens were categorized according to the UICC 2002 TNM classification. A subset of patients was operatively staged with regard to lymph node status. A commercially available Real Time PCR was used to detect 13 different types of HPV (6,11,16,18,31,33,35,45,51,52,56,58 and 59).

    RESULTS: We excluded 25 patients due to low DNA quality. Of the remaining 216, 179 (82.9%) tumour specimens were HPV infected. The majority of cases positive for HPV (70.4%) were infected by a single-type. The most frequent type was HPV 16 followed by HPV 18. No significant association between HPV status and pathological tumour stage, grade or lymph node status was found.

    CONCLUSION: The HPV prevalence found is higher than in most other studies, further strengthening HPV as an etiological agent in penile carcinoma. Furthermore, the high prevalence of HPV 16 and 18 raises the question of what potential impact current HPV vaccines that target these specific HPV types might have on penile carcinoma. No significant association between HPV status and histopathological parameters was found in the present study. Additional investigations are needed to draw final conclusions on the prognostic value of HPV status in penile carcinoma.

  • 46.
    Kirrander, Peter
    et al.
    Örebro University Hospital, Örebro, Sweden.
    Kolaric, Aleksandra
    Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Örebro University Hospital, Örebro, Sweden.
    Windahl, Torgny
    Örebro University Hospital, Örebro, Sweden.
    Andrén, Ove
    Örebro University Hospital, Örebro, Sweden.
    Stark, Jennifer Rider
    Örebro University Hospital, Örebro, Sweden; Brigham & Women’s Hospital, Boston MA, USA; Harvard Medical School, Boston MA, USA.
    Lillsunde-Larsson, Gabriella
    Örebro University Hospital, Örebro, Sweden.
    Elgh, Fredrik
    Örebro University, School of Health and Medical Sciences. Umeå University, Umeå, Sweden.
    Karlsson, Mats G.
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Human papillomavirus prevalence, distribution and correlation to histopathological parameters in a large Swedish cohort of men with penile carcinoma2011In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 108, no 3, p. 355-359Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To analyse the overall and type-specific human papillomavirus (HPV) prevalence and distribution in penile carcinoma and determine the correlation to histopathological parameters.

    PATIENTS AND METHODS In this retrospective study, we analysed HPV status in 241 patients with penile carcinoma, treated at Orebro University Hospital, Orebro, Sweden, between 1984 and 2008. Age and date at diagnosis was recorded. The tumour specimens were categorized according to the UICC 2002 TNM classification. A subset of patients was operatively staged with regard to lymph node status. A commercially available Real Time PCR was used to detect 13 different types of HPV (6,11,16,18,31,33,35,45,51,52,56,58 and 59).

    RESULTS We excluded 25 patients due to low DNA quality. Of the remaining 216, 179 (82.9%) tumour specimens were HPV infected. The majority of cases positive for HPV (70.4%) were infected by a single-type. The most frequent type was HPV 16 followed by HPV 18. No significant association between HPV status and pathological tumour stage, grade or lymph node status was found.

    CONCLUSION The HPV prevalence found is higher than in most other studies, further strengthening HPV as an etiological agent in penile carcinoma. Furthermore, the high prevalence of HPV 16 and 18 raises the question of what potential impact current HPV vaccines that target these specific HPV types might have on penile carcinoma. No significant association between HPV status and histopathological parameters was found in the present study. Additional investigations are needed to draw final conclusions on the prognostic value of HPV status in penile carcinoma.

  • 47.
    Kirrander, Peter
    et al.
    Orebro Univ Hosp, Dept Urol, SE-70185 Orebro, Sweden..
    Sherif, Amir
    Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Friedrich, Bengt
    Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Lambe, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Håkansson, Ulf
    Skane Univ, Dept Urol, Malmo, Sweden..
    Swedish National Penile Cancer Register: incidence, tumour characteristics, management and survival2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 2, p. 287-292Article in journal (Refereed)
    Abstract [en]

    Objectives To assess penile cancer incidence, stage distribution, adherence to guidelines and prognostic factors in a population-based setting. Patients and Methods The population-based Swedish National Penile Cancer Register (NPECR) contains detailed information on tumour characteristics and management patterns. A total of 1 678 men with primary squamous cell carcinoma of the penis identified in the NPECR between 2000 and 2012 were included in the study. Results The mean age-adjusted incidence of penile cancer was 2.1/100 000 men, remaining virtually unchanged during the study period. At diagnosis, 14 and 2% of the men had clinical N+ and M+ disease, respectively. Most men were staged pTis (34%), pT2 (19%), or pT1 (18%), while stage information was unavailable for 18% of the men. Organ-preserving treatment was used in 71% of Tis-T1 tumours. Of men with cN0 and >= pT1G2 disease, 50% underwent lymph node staging, while 74% of men with cN1-3 disease underwent lymph node dissection. The overall 5-year relative survival rate was 82%. Men aged >= 40 years and those with pT2-3, G2-3 and N+ tumours had worse outcomes. Conclusions The incidence of penile cancer in Sweden is stable. Most men presented with localized disease, and the proportion of non-invasive tumours was high. During the period under study, adherence to guidelines was suboptimum. The overall 5-year relative survival rate was 82%. Older age, increasing tumour stage and grade, and increasing lymph node stage were associated with poorer survival.

  • 48.
    Kirrander, Peter
    et al.
    Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Sherif, Amir
    Dept Surg & Perioperat Sci, Urol & Androl, Umeå Univ, Umeå, Sweden.
    Friedrich, Bengt
    Dept Surg & Perioperat Sci, Urol & Androl, Umeå Univ, Umeå, Sweden.
    Lambe, Mats
    Reg Canc Ctr Uppsala Orebro, Uppsala Univ, Uppsala, Sweden; Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
    Håkansson, Ulf
    Dept Urol, Skåne Univ, Malmö, Sweden.
    Swedish National Penile Cancer Register: incidence, tumour characteristics, management and survival2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 2, p. 287-292Article in journal (Refereed)
    Abstract [en]

    Objectives: To assess penile cancer incidence, stage distribution, adherence to guidelines and prognostic factors in a population-based setting.

    Patients and Methods: The population-based Swedish National Penile Cancer Register (NPECR) contains detailed information on tumour characteristics and management patterns. A total of 1 678 men with primary squamous cell carcinoma of the penis identified in the NPECR between 2000 and 2012 were included in the study.

    Results: The mean age-adjusted incidence of penile cancer was 2.1/100 000 men, remaining virtually unchanged during the study period. At diagnosis, 14 and 2% of the men had clinical N+ and M+ disease, respectively. Most men were staged pTis (34%), pT2 (19%), or pT1 (18%), while stage information was unavailable for 18% of the men. Organ-preserving treatment was used in 71% of Tis-T1 tumours. Of men with cN0 and >= pT1G2 disease, 50% underwent lymph node staging, while 74% of men with cN1-3 disease underwent lymph node dissection. The overall 5-year relative survival rate was 82%. Men aged >= 40 years and those with pT2-3, G2-3 and N+ tumours had worse outcomes.

    Conclusions: The incidence of penile cancer in Sweden is stable. Most men presented with localized disease, and the proportion of non-invasive tumours was high. During the period under study, adherence to guidelines was suboptimum. The overall 5-year relative survival rate was 82%. Older age, increasing tumour stage and grade, and increasing lymph node stage were associated with poorer survival.

  • 49.
    Kirrander, Peter
    et al.
    Örebro, Sweden.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Friedrich, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lambe, Mats
    Uppsala, Sweden; Stockholm, Sweden.
    Håkansson, Ulf
    Malmö, Sweden.
    The Swedish National Penile Cancer Register: Incidence, Tumour Characteristics, Management and Survival2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 2, p. 287-292Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:  To assess penile cancer incidence, stage distribution, adherence to guidelines, and prognostic factors in a population-based setting.

    PATIENTS AND METHODS:  The population-based Swedish National Penile Cancer Register (NPECR) contains detailed information on tumour characteristics and management patterns. ● A total of 1678 men with primary squamous cell carcinoma of the penis identified in the NPECR between 2000 and 2012 were included in the study. 

    RESULTS:  The mean age-adjusted incidence of penile cancer was 2.1/100,000 men, remaining virtually unchanged during the study period. At diagnosis, 14% and 2% were clinically N+ and M+, respectively. Most patients were staged pTis (34%), pT2 (19%), or pT1 (18%), whereas stage was unavailable in 18%. Organ-preserving treatment was used in 71% of Tis-T1 tumours. In cN0 and ≥pT1G2 patients, 50% underwent lymph node staging, while 74% of cN1-3 patients underwent lymph node dissection. The overall 5-year relative survival was 82%. Men aged ≥40 years and those with pT2-3, G2-3 and N+ tumours had worse outcome.

    CONCLUSION: The incidence of penile cancer in Sweden is stable. Most men presented with localised disease, and the proportion of non-invasive tumours was high. During the period under study, adherence to guidelines was suboptimal. The overall 5-year relative survival was 82%. Older age, increasing tumour stage and grade, and increasing lymph node stage were associated with poorer survival.

  • 50.
    Klaff, Rami
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Berglund, Anders
    Eksatravagen 72, Uppsala, Sweden.
    Varenhorst, Eberhard
    Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Olov Hedlund, Per
    Karolinska Institute Solna, Sweden.
    Nler, Morten J.
    Aalborg University Hospital, Denmark.
    Sandblom, Gabriel
    Karolinska Hospital Huddinge, Sweden.
    Clinical characteristics and quality-of-life in patients surviving a decade of prostate cancer with bone metastases2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 6, p. 904-913Article in journal (Refereed)
    Abstract [en]

    Objective To describe characteristics and quality-of-life (QoL), and to define factors associated with long-term survival in a subgroup of patients with prostate cancer with M1b disease. Patients and Methods The study was based on 915 patients from a prospective randomised multicentre trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Long-term survival was defined as patients having an overall survival of &gt;= 10 years, and logistic regression models were constructed to identity clinical predictors of survival. QoL during follow-up was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - C30 version 1 (EORTC-C30) ratings. Results In all, 40 (4.4%) of the 915 men survived for &gt;10 years. Factors significantly associated with increased likelihood of surviving for &gt;10 years in the univariate analyses were: absence of cancer-related pain; Eastern Cooperative Oncology Group (ECOG) performance status of &lt;2; negligible analgesic consumption; T-category of 1-2; prostate-specific antigen (PSA) level of &lt;231 mu g/L; and a Soloway score of 1. In the multivariate analyses, ECOG performance status of &lt;2, PSA level of &lt;231 mu g/L, and Soloway score of 1, were all independent predictors of long-term survival. All subscales of the EORTC-C30 were higher in this group than for patients with short survival, but slowly declined over the decade. Conclusion A subgroup of patients with prostate cancer with M1b disease and certain characteristics showed a positive long-term response to androgen-deprivation therapy with an acceptable QoL over a decade or more. Independent predictors of long-term survival were identified as ECOG performance status of &lt;2, limited extent of bone metastases (Soloway score of 1), and a PSA level of &lt;231 mu g/L at the time of enrolment.

123 1 - 50 of 114
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf