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  • 1.
    Aizawa, Naoki
    et al.
    University of Tokyo, Japan.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Fuellhase, Claudius
    University of Munich, Germany.
    Ito, Hiroki
    University of Tokyo, Japan.
    Homma, Yukio
    University of Tokyo, Japan.
    Igawa, Yasuhiko
    University of Tokyo, Japan .
    Inhibition of Peripheral FAAH Depresses Activities of Bladder Mechanosensitive Nerve Fibers of the Rat2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 3, p. 956-963Article in journal (Refereed)
    Abstract [en]

    Purpose: FAAH degrades endocannabinoids and fatty acid amides. FAAH inhibition reduces micturition frequency and counteracts bladder overactivity in rats. We studied the effects of the peripherally active selective FAAH inhibitor URB937, and the CB1 and CB2 receptor antagonists rimonabant and SR144528, respectively, on single unit afferent activity of primary bladder afferents in rats. Materials and Methods: Female Sprague Dawley (R) rats were anesthetized. Single unit afferent activity of A delta or C-fibers from the L6 dorsal roots was recorded during bladder filling before and after URB937 administration with or without rimonabant or SR144528. Drugs (1 mg/kg) were given intravenously. FAAH, CB1 and CB2 expression, and expression of the sensory marker CGRP in the L6 dorsal root ganglion were compared by immunofluorescence. Results: A total of 102 single afferent fibers (48 A delta and 54 C-fibers) were isolated from 57 rats. URB937 decreased single unit afferent activity of C-fibers to a mean +/- SEM of 78% +/- 9% and of A delta-fibers to a mean of 67% +/- 7% while increasing bladder compliance to a mean of 116% +/- 3%. The effects of URB937 on single unit afferent activity and bladder compliance were counteracted by rimonabant or SR144528. Rimonabant increased single unit afferent activity of each fiber type but SR144528 affected only A delta-fiber activity. CGRP positive L6 dorsal root ganglion neurons showed strong FAAH, CB1 and CB2 staining. Conclusions: To our knowledge we report for the first time that inhibiting peripheral FAAH depresses the Ad and C-fiber activity of primary bladder afferents via CB1 and CB2 receptors. CB antagonists alone exerted facilitatory effects on single unit afferent activity during bladder filling in rats. The endocannabinoid system may be involved in physiological control of micturition as regulators of afferent signals.

  • 2.
    Andersson, Patiyan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Kolaric, Aleksandra
    Departments of Pathology, Örebro University Hospital, Örebro, Sweden.
    Windahl, Torgny
    Departments of Urology, Örebro University Hospital, Örebro, Sweden.
    Kirrander, Peter
    Departments of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Karlsson, Mats G.
    Departments of b Pathology, Örebro University Hospital, Örebro, Sweden.
    PIK3CA, HRAS and KRAS gene mutations in human penile cancer2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 5, p. 2030-2034 Article in journal (Refereed)
    Abstract [en]

    Purpose: The knowledge of somatic mutations that arise in penile cancer is limited. We examined the dysregulation of components in the phosphatidylinositol 3-kinase and Ras pathways.

    Materials and Methods: Using single stranded conformational analysis and direct sequencing we performed mutational analysis of the PIK3CA, PTEN, HRAS, KRAS, NRAS and BRAF genes in 28 penile tumors.

    Results: We identified somatic missense mutations in 11 of the 28 penile cancer samples (39%). In the PIK3CA gene 8 mutations (29%) were identified that were E542K or E545K. In the HRAS gene a G12S and a Q61L mutation were found (7%). The KRAS gene contained 1 mutation (3%), that is a G12S change. PIK3CA mutations were found in all grades and stages, whereas HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma.

    Conclusions: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.

  • 3.
    Andersson, Patiyan
    et al.
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Kolaric, Aleksandra
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Windahl, Torgny
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Kirrander, Peter
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderkvist, Peter
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Karlsson, Mats G
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    PIK3CA, HRAS and KRAS gene mutations in human penile cancer2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 5, p. 2030-2034Article in journal (Refereed)
    Abstract [en]

    Purpose: The knowledge of somatic mutations that arise in penile cancer is limited. We examined the dysregulation of components in the phosphatidylinositol 3-kinase and Ras pathways.

    Materials and Methods: Using single stranded conformational analysis and direct sequencing we performed mutational analysis of the PIK3CA, PTEN, HRAS, KRAS, NRAS and BRAF genes in 28 penile tumors.

    Results: We identified somatic missense mutations in 11 of the 28 penile cancer samples (39%). In the PIK3CA gene 8 mutations (29%) were identified that were E542K or E545K. In the HRAS gene a G12S and a Q61L mutation were found (7%). The KRAS gene contained 1 mutation (3%), that is a G12S change. PIK3CA mutations were found in all grades and stages, whereas HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma.

    Conclusions: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.

  • 4.
    Andrén, Ove
    et al.
    Örebro University, Department of Clinical Medicine.
    Fall, Katja
    Franzén, Lennart
    Andersson, Swen-Olof
    Johansson, Jan-Erik
    Rubin, Mark A.
    How well does the Gleason score predict prostate cancer death?: A 20-year followup of a population based cohort in Sweden2006In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 175, no 4, p. 1337-1340Article in journal (Refereed)
    Abstract [en]

    Purpose

    Adenocarcinoma of the prostate is the most common cancer among men in Western countries. Although the prognostic heterogeneity of prostate cancer is enormous, clinically insignificant aggressive prostate cancers cannot be reliably distinguished. Therefore, identifying prognostic factors is increasingly important, notably among men diagnosed with localized prostate cancer, because many of them may not require aggressive treatment.

    Materials and Methods

    We analyzed a population based cohort of 253 men with early stage (T1a-b, Nx, M0) initially untreated prostate cancer diagnosed between 1977 and 1991, before PSA screening was available. Tissue samples were available for 240 patients diagnosed with transurethral resection. During complete followup through September 2003, standardized criteria were used to classify histopathological characteristics, progression and causes of death.

    Results

    Higher Gleason grade, higher nuclear grade and larger tumor volume were independent predictors of death in prostate cancer with monotonous and statistically significant trends (p <0.05). In contrast, the level of Ki-67 – strongly correlated to Gleason score – was not an independent predictor of prostate cancer death. Given a Gleason score of 7 or greater, the probability of dying of prostate cancer was 29%. The corresponding predictive value for Gleason score 8 or greater was 48%.

    Conclusions

    Although a high Gleason score is a determinant of prostate cancer death, its PPV is relatively low. Thus, further efforts in finding other or complementary indicators of prostate cancer outcome are needed.

  • 5.
    Austin, Paul F
    et al.
    Division of Urology, Washington University in St. Louis, St. Louis Children’s Hospital, Missouri.
    Bauer, Stuart B
    Department of Urology, Children’s Hospital and Harvard Medical School, Boston, Massachusetts.
    Bower, Wendy
    Pediatrics (Nephrology Section), Skejby University Hospital, Aarhus, Denmark.
    Chase, Janet
    The Children’s Centre, Cabrini Hospital, Melbourne, Australia.
    Franco, Israel
    New York Medical College, Valhalla, New York.
    Hoebeke, Piet
    Pediatric Urology and Nephrology, Gent University Hospital, Ghent, Belgium.
    Rittig, Søren
    Pediatrics (Nephrology Section), Skejby University Hospital, Aarhus, Denmark.
    Walle, Johan Vande
    Pediatric Urology and Nephrology, Gent University Hospital, Ghent, Belgium.
    von Gontard, Alexander
    Department of Child and Adolescent Psychiatry, Saarland University Hospital, Homburg, Germany.
    Wright, Anne
    Pediatrics, Evelina Children’s Hospital, St Thomas’ Hospital, London, England.
    Yang, Stephen S
    Division of Urology, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, New Taipei.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    The Standardization of Terminology of Lower Urinary Tract Function in Children and Adolescents: Update Report from the Standardization Committee of the International Children's Continence Society.2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, no 6, p. 1863-1865Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The impact of the original International Children's Continence Society (ICCS) terminology document on lower urinary tract (LUT) function resulted in the global establishment of uniformity and clarity in the characterization of LUT function and dysfunction in children across multiple healthcare disciplines. The present document serves as a stand-alone terminology update reflecting refinement and current advancement of knowledge on pediatric LUT function.

    MATERIALS AND METHODS: A variety of worldwide experts from multiple disciplines within the ICCS leadership who care for children with LUT dysfunction were assembled as part of the standardization committee. A critical review of the previous ICCS terminology document and the current literature was performed. Additionally, contributions and feedback from the multidisciplinary ICCS membership were solicited.

    RESULTS: Following a review of the literature over the last 7 years, the ICCS experts assembled a new terminology document reflecting current understanding of bladder function and LUT dysfunction in children using the resources from the literature review, expert opinion and ICCS member feedback.

    CONCLUSIONS: The present ICCS terminology document provides a current and consensus update to the evolving terminology and understanding of LUT function in children.

  • 6. Barker, G. M.
    et al.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Arnell, Kai
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Distal shunt obstruction in children with meningomyelocele after bladder perforation2006In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 176, no 4 Pt 2, p. 1726-1728Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We studied short-term complications and particularly the signs of shunt dysfunction after augmented bladder perforation in patients with myelomeningocele and ventriculoperitoneal shunts. MATERIALS AND METHODS: In our series of bladder augmentations in 27 patients with myelomeningocele and a ventriculoperitoneal shunt in the last 10 years (1994 to 2004) we noted 4 who were 8 to 16 years old at our institute with bladder perforation 2 to 5 years after augmentation. Three patients received a colonic augmentation and 1 received an ileal augmentation. One patient underwent surgery for small bowel obstruction 2 years after the primary operation, when a hole in the augmented bladder was identified and oversewn. The other 3 bladder perforations occurred spontaneously or after failure to catheterize. An additional patient with spontaneous perforation underwent auto-augmentation elsewhere. RESULTS: After primary open abdominal surgery and enterocystoplasty there was no sign of shunt dysfunction in any patient. Bladder perforation and leakage of free urine into the abdominal cavity occurred in 4 of the 5 patients. In those patients severe symptoms of shunt dysfunction, including headache and high intracranial pressure, were noted 2 to 7 days after perforation. In patient 1 there was only urine leakage into a small cavity close to the bladder and no acute signs of post-perforation shunt dysfunction. In all cases the shunt was externalized for 1 to 6 weeks without further complications. CONCLUSIONS: In patients with myelodysplasia who have bladder perforation and free urine in the abdominal cavity the peritoneum is chemically inflamed by urine. Resorption of cerebral liquor may be disturbed, leading to shunt dysfunction and high intracranial pressure. Therefore, it is important for the urologist to recognize and evaluate postoperative signs and symptoms of increased intracerebral pressure in patients with bladder perforation. If found, early computerized tomography of the brain is recommended.

  • 7. Bechis, Seth K
    et al.
    Otsetov, Alexander G
    Ge, Rongbin
    Olumi, Aria F
    Personalized medicine for the management of benign prostatic hyperplasia.2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 1Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Benign prostatic hyperplasia affects more than 50% of men by age 60 years, and is the cause of millions of dollars in health care expenditure for the treatment of lower urinary tract symptoms and urinary obstruction. Despite the widespread use of medical therapy, there is no universal therapy that treats all men with symptomatic benign prostatic hyperplasia. At least 30% of patients do not respond to medical management and a subset require surgery. Significant advances have been made in understanding the natural history and development of the prostate, such as elucidating the role of the enzyme 5α-reductase type 2, and advances in genomics and biomarker discovery offer the potential for a more targeted approach to therapy. We review the current understanding of benign prostatic hyperplasia progression as well as the key genes and signaling pathways implicated in the process such as 5α-reductase. We also explore the potential of biomarker screening and gene specific therapies as tools to risk stratify patients with benign prostatic hyperplasia and identify those with symptomatic or medically resistant forms.

    MATERIALS AND METHODS: A PubMed® literature search of current and past peer reviewed literature on prostate development, lower urinary tract symptoms, benign prostatic hyperplasia pathogenesis, targeted therapy, biomarkers, epigenetics, 5α-reductase type 2 and personalized medicine was performed. An additional Google Scholar™ search was conducted to broaden the scope of the review. Relevant reviews and original research articles were examined, as were their cited references, and a synopsis of original data was generated with the goal of informing the practicing urologist of these advances and their implications.

    RESULTS: Benign prostatic hyperplasia is associated with a state of hyperplasia of the stromal and epithelial compartments, with 5α-reductase type 2 and androgen signaling having key roles in the development and maintenance of the prostate. Chronic inflammation, multiple growth factor and hormonal signaling pathways, and medical comorbidities have complex roles in prostate tissue homeostasis as well as its evolution into the clinical state of benign prostatic hyperplasia. Resistance to medical therapy with finasteride may occur through silencing of the 5α-reductase type 2 gene by DNA methylation, leading to a state in which 30% of adult prostates do not express 5α-reductase type 2. Novel biomarkers such as single nucleotide polymorphisms may be used to risk stratify patients with symptomatic benign prostatic hyperplasia and identify those at risk for progression or failure of medical therapy. Several inhibitors of the androgen receptor and other signaling pathways have recently been identified which appear to attenuate benign prostatic hyperplasia progression and may offer alternative targets for medical therapy.

    CONCLUSIONS: Progressive worsening of lower urinary tract symptoms and bladder outlet obstruction secondary to benign prostatic hyperplasia is the result of multiple pathways including androgen receptor signaling, proinflammatory cytokines and growth factor signals. New techniques in genomics, proteomics and epigenetics have led to the discovery of aberrant signaling pathways, novel biomarkers, DNA methylation signatures and potential gene specific targets. As personalized medicine continues to develop, the ability to risk stratify patients with symptomatic benign prostatic hyperplasia, identify those at higher risk for progression, and seek alternative therapies for those in whom conventional options are likely to fail will become the standard of targeted therapy.

  • 8. Bechis, Seth K
    et al.
    Otsetov, Alexander G
    Ge, Rongbin
    Wang, Zongwei
    Vangel, Mark G
    Wu, Chin-Lee
    Tabatabaei, Shahin
    Olumi, Aria F
    Age and Obesity Promote Methylation and Suppression of 5α-Reductase 2: Implications for Personalized Therapy of Benign Prostatic Hyperplasia.2015In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, no 4Article in journal (Refereed)
    Abstract [en]

    PURPOSE: In men with symptomatic benign prostatic hyperplasia 5α-reductase inhibitors are a main modality of treatment. More than 30% of men do not respond to the therapeutic effects of 5α-reductase inhibitors. We have found that a third of adult prostate samples do not express 5α-reductase type 2 secondary to epigenetic modifications. We evaluated whether 5α-reductase type 2 expression in benign prostatic hyperplasia specimens from symptomatic men was linked to methylation of the 5α-reductase type 2 gene promoter. We also identified associations with age, obesity, cardiac risk factors and prostate specific antigen.

    MATERIALS AND METHODS: Prostate samples from men undergoing transurethral prostate resection were used. We determined 5α-reductase type 2 protein expression and gene promoter methylation status by common assays. Clinical variables included age, body mass index, hypertension, hyperlipidemia, diabetes, prostate specific antigen and prostate volume. Univariate and multivariate statistical analyses were performed followed by stepwise logistic regression modeling.

    RESULTS: Body mass index and age significantly correlated with methylation of the 5α-reductase type 2 gene promoter (p <0.05) whereas prostate volume, prostate specific antigen or benign prostatic hyperplasia medication did not correlate. Methylation highly correlated with 5α-reductase protein expression (p <0.0001). In a predictive model increasing age and body mass index significantly predicted methylation status and protein expression (p <0.01).

    CONCLUSIONS: Increasing age and body mass index correlate with increased 5α-reductase type 2 gene promoter methylation and decreased protein expression in men with symptomatic benign prostatic hyperplasia. These results highlight the interplay among age, obesity and gene regulation. Our findings suggest an individualized epigenetic signature for symptomatic benign prostatic hyperplasia, which may be important to choose appropriate personalized treatment options.

  • 9. Berglund, Anders
    et al.
    Garmo, Hans
    Tishelman, Carol
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stattin, Pär
    Lambe, Mats
    Comorbidity, treatment and mortality: a population based cohort study of prostate cancer in PCBaSe Sweden2011In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 185, no 3, p. 833-840Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    We examined associations among comorbidity, treatment decisions and mortality in patients with prostate cancer.

    MATERIALS AND METHODS:

    A total of 77,536 men diagnosed with prostate cancer between 1997 and 2006 were identified in PCBaSe Sweden from the National Prostate Cancer Register of Sweden. Logistic, Cox and competing risk regression were used to assess associations among Charlson comorbidity index, treatment and mortality. The Charlson comorbidity index was categorized into no (0), mild (1) and severe comorbidity (2+).

    RESULTS:

    In men with low risk prostate cancer 5,975 of the 13,245 (45.1%) patients without comorbidity underwent radical prostatectomy compared to 256 of the 1,399 (18.9%) men with severe comorbidity. Following adjustment for age and period of diagnosis, radical prostatectomy was less likely to be offered to men with severe comorbidity (OR 0.48, 95% CI 0.41-0.55). In men with high risk prostate cancer, radiotherapy was more common (range 7.7% to 21.3%) than radical prostatectomy (range 3.0% to 11.2%) regardless of comorbidity burden. All cause and competing cause but not prostate cancer specific mortality were increased in men with severe comorbidity (all cause HR 1.99, 95% CI 1.93-2.05; competing cause sHR 2.66, 95% CI 2.56-2.78; prostate cancer specific sHR 0.98, 95% CI 0.93-1.03). The cumulative probability of prostate cancer death given no death from competing causes was significantly higher in men with severe comorbidity in all risk groups (p<0.01).

    CONCLUSIONS:

    Comorbidity affects treatment choices, and is associated with all cause, competing cause and conditional prostate cancer specific mortality. An increased conditional prostate cancer specific mortality in men with severe comorbidity may reflect less aggressive treatment, impaired tumor defense, lifestyle factors and poor general health behavior.

  • 10. Berglund, Anders
    et al.
    Garmo, Hans
    Tishelman, Carol
    Holmberg, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lambe, Mats
    Comorbidity, treatment and mortality: a population based cohort study of prostate cancer in PCBaSe Sweden2011In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 185, no 3, p. 833-840Article in journal (Refereed)
    Abstract [en]

    Purpose

    We examined associations among comorbidity, treatment decisions and mortality in patients with prostate cancer.

    Materials and Methods

    A total of 77,536 men diagnosed with prostate cancer between 1997 and 2006 were identified in PCBaSe Sweden from the National Prostate Cancer Register of Sweden. Logistic, Cox and competing risk regression were used to assess associations among Charlson comorbidity index, treatment and mortality. The Charlson comorbidity index was categorized into no (0), mild (1) and severe comorbidity (2+).

    Results

    In men with low risk prostate cancer 5,975 of the 13,245 (45.1%) patients without comorbidity underwent radical prostatectomy compared to 256 of the 1,399 (18.9%) men with severe comorbidity. Following adjustment for age and period of diagnosis, radical prostatectomy was less likely to be offered to men with severe comorbidity (OR 0.48, 95% CI 0.41–0.55). In men with high risk prostate cancer, radiotherapy was more common (range 7.7% to 21.3%) than radical prostatectomy (range 3.0% to 11.2%) regardless of comorbidity burden. All cause and competing cause but not prostate cancer specific mortality were increased in men with severe comorbidity (all cause HR 1.99, 95% CI 1.93–2.05; competing cause sHR 2.66, 95% CI 2.56–2.78; prostate cancer specific sHR 0.98, 95% CI 0.93–1.03). The cumulative probability of prostate cancer death given no death from competing causes was significantly higher in men with severe comorbidity in all risk groups (p <0.01).

    Conclusions

    Comorbidity affects treatment choices, and is associated with all cause, competing cause and conditional prostate cancer specific mortality. An increased conditional prostate cancer specific mortality in men with severe comorbidity may reflect less aggressive treatment, impaired tumor defense, lifestyle factors and poor general health behavior.

  • 11.
    Berrum-Svennung, Ingela
    et al.
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.
    Granfors, Torvald
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Jahnson, Staffan
    Boman, Hans
    Lasarettet, Dept Urol, Alingsas, Sweden.
    Holmang, Sten
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.
    A single instillation of epirubicin after transurethral resection of bladder tumors prevents only small recurrences2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 1, p. 101-105Article in journal (Refereed)
    Abstract [en]

    Purpose: We studied whether a single instillation of epirubicin after transurethral bladder tumor resection would influence the interval to and size of the first recurrence. Materials and Methods: A total of 404 patients from 13 hospitals were randomized to 1 instillation of 50 mg epirubicin or placebo within 6 hours after transurethral resection of bladder tumors. Results: Of 155 evaluable patients in the epirubicin group 79 (51.0%) had recurrence compared to 95 of 152 (62.5%) in the placebo group (p = 0.04). Of the recurrences 63.3% were small (1 to 5 mm). Tumor size was unknown in 5 patients. Of 79 patients with recurrence in the epirubicin arm 33 (42.9%) vs 29 (31.5%) of 95 in the placebo arm had larger (more than 5 mm) first recurrences (p = 0.12). Approximately half of the patients with first recurrences were treated as outpatients and the other half spent a total of 145 days in the hospital with no difference between the groups. Conclusions: We confirmed the results of previous studies showing that 8.5 patients must be treated with a single instillation to prevent I recurrence. Furthermore, our data may indicate that only small recurrences are prevented, which could easily be fulgurated using local anesthesia at followup cystoscopy. The benefit of single instillations can be questioned if this finding is confirmed by others.

  • 12.
    Beukers, Willemien
    et al.
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    van der Keur, Kirstin A.
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    Kandimalla, Raju
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    Vergouwe, Yvonne
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands..
    Steyerberg, Ewout W.
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands..
    Boormans, Joost L.
    Erasmus MC, Dept Urol, Rotterdam, Netherlands..
    Jensen, Jorgen B.
    Aarhus Univ Hosp, Dept Urol, Aarhus, Denmark..
    Lorente, Jose A.
    Hosp del Mar, Serv Urol, Barcelona, Spain..
    Real, Francisco X.
    Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.;Spanish Natl Canc Res Centre CNIO, Canc Cell Biol Programme, Epithelial Carcinogenesis Grp, Madrid, Spain..
    Segersten, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Orntoft, Torben F.
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Malats, Nuria
    Spanish Natl Canc Res Centre CNIO, Canc Cell Biol Programme, Epithelial Carcinogenesis Grp, Madrid, Spain..
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Dyrskjot, Lars
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Zwarthoff, Ellen C.
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    FGFR3, TERT and OTX1 as a Urinary Biomarker Combination for Surveillance of Patients with Bladder Cancer in a Large Prospective Multicenter Study2017In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 197, no 6, p. 1410-1418Article in journal (Refereed)
    Abstract [en]

    Purpose: Patients with nonmuscle invasive bladder cancer are followed with frequent cystoscopies. In this study FGFR3, TERT and OTX1 were investigated as a diagnostic urinary marker combination during followup of patients with primary nonmuscle invasive bladder cancer.

    Materials and Methods: In this international, multicenter, prospective study 977 patients with nonmuscle invasive bladder cancer were included. A total of 2,496 urine samples were collected prior to cystoscopy during regular visits. Sensitivity was estimated to detect concomitant recurrences. Kaplan-Meier curves were used to estimate the development of future recurrences after urinalysis and a negative cystoscopy.

    Results: Sensitivity of the assay combination for recurrence detection was 57% in patients with primary low grade, nonmuscle invasive bladder cancer. However, sensitivity was 83% for recurrences that were pT1 or muscle invasive bladder cancer. Of the cases 2% progressed to muscle invasive bladder cancer. Sensitivity for recurrence detection in patients with primary high grade disease was 72% and 7% of them had progression to muscle invasive bladder cancer. When no concomitant tumor was found by cystoscopy, positive urine samples were more frequently followed by a recurrence over time compared to a negative urine sample (58% vs 36%, p < 0.001). High stage recurrences were identified within 1 year after a positive urine test and a negative cystoscopy.

    Conclusions: Recurrences in patients with primary nonmuscle invasive bladder cancer can be detected by a combination of urine assays. This study supports the value of urinalysis as an alternative diagnostic tool in patients presenting with low grade tumors and as a means to identify high stage tumors earlier.

  • 13.
    Bill-Axelson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Norlén, Bo Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Norberg, Mona
    No increased prostate cancer incidence after negative transrectal ultrasound guided multiple biopsies in men with increased prostate specific antigen and/or abnormal digital rectal examination.2003In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 170, no 4 Pt 1, p. 1180-3Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We investigated the incidence of prostate cancer after negative transrectal ultrasound (TRUS) guided multiple biopsies. Our secondary aim was to calculate the sensitivity of the extended protocol used.

    MATERIALS AND METHODS: A cohort of 547 men with elevated prostate specific antigen and/or abnormal digital rectal examination but with results negative for prostate cancer on a mean of 9 TRUS guided biopsies was followed through record linkage to the national cancer Registry. The observed number of prostate cancers was compared with the expected number during the same calendar period in an age matched male population to determine the standardized incidence ratio. The sensitivity of TRUS with multiple biopsies after 5 years of followup was calculated. Relative survival was estimated if there was an excess death rate due to undiagnosed prostate cancer.

    RESULTS: We found 11 men diagnosed with prostate cancer. The expected number in the age standardized male population was 15, resulting in a standardized incidence ratio of 0.8 (95% CI 0.4 to 1.2). Five-year sensitivity of the extended protocol of TRUS guided biopsies was 95.2% (95% CI 93.5 to 96.4) and relative survival was more than 100%, indicating a selection of men deemed candidates for curative treatment.

    CONCLUSIONS: Men with clinical suspicion of prostate cancer who are examined by an extended protocol of TRUS guided biopsies negative for cancer do not have an increased incidence of prostate cancer within 6 years compared with an age matched male population. Five-year sensitivity of this protocol was high.

  • 14.
    Brandström, Per
    et al.
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Esbjörner, Elisabeth
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Herthelius, Maria
    Department for Clinical Science, Intervention and Technology, Karolinska University Hospital, Huddinge, Sweden.
    Holmdahl, Gundela
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sillén, Ulla
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Sixt, Rune
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Sjöberg, Ingrid
    Department of Pediatrics, Children's University Hospital, Lund, Sweden.
    Stokland, Eira
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Jodal, Ulf
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Hansson, Sverker
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    The Swedish reflux trial in children: I. Study design and study population characteristics2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, no 1, p. 274-279Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We compared the rates of febrile urinary tract infection, kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways, including antibiotic prophylaxis, endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection. MATERIALS AND METHODS: Children 1 to younger than 2 years with grade III-IV reflux were recruited into this prospective, open, randomized, controlled, multicenter study and followed for 2 years after randomization. The main study end points were recurrent febrile urinary tract infection, renal status on dimercapto-succinic acid scintigraphy and reflux status. Outcomes were analyzed by the intent to treat principle. RESULTS: During a 6-year period 128 girls and 75 boys entered the study. In 96% of cases reflux was detected after urinary tract infection. The randomization procedure was successful and resulted in 3 groups matched for relevant factors. Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good. Of the children 93% were followed for the intended 2 years without a treatment arm change. All except 2 patients completed 2-year followup scintigraphy. CONCLUSIONS: Recruitment was difficult but a substantial number of children were entered and randomly assigned to 3 groups with similar basic characteristics. Good adherence to the protocol made it possible to address the central study questions.

  • 15.
    Brandström, Per
    et al.
    Pediatric Uro-Nephrologic Center, The Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sixt, Rune
    Pediatric Uro-Nephrologic Center, The Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Stokland, Eira
    Pediatric Uro-Nephrologic Center, The Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Jodal, Ulf
    Pediatric Uro-Nephrologic Center, The Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Hansson, Sverker
    Pediatric Uro-Nephrologic Center, The Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    The Swedish reflux trial in children: IV. Renal damage2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, no 1, p. 292-297Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We compared the development of new renal damage in small children with dilating vesicoureteral reflux randomly allocated to antibiotic prophylaxis, endoscopic treatment or surveillance as the control group. MATERIALS AND METHODS: Included in the study were 128 girls and 75 boys 1 to younger than 2 years with grade III-IV reflux. Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before randomization and after 2 years. Febrile urinary tract infections were recorded during followup. Data analysis was done by the intent to treat principle. RESULTS: New renal damage in a previously unscarred area was seen in 13 girls and 2 boys. Eight of the 13 girls were on surveillance, 5 received endoscopic therapy and none were on prophylaxis (p = 0.0155). New damage was more common in children with than without febrile recurrence (11 of 49 or 22% vs 4 of 152 or 3%, p <0.0001). CONCLUSIONS: In boys the rate of new renal damage was low. It was significantly higher in girls and most common in the control surveillance group. There was also a strong association between recurrent febrile UTIs and new renal damage in girls.

  • 16. Carter, H Ballentine
    et al.
    Albertsen, Peter C
    Barry, Michael J
    Etzioni, Ruth
    Freedland, Stephen J
    Greene, Kirsten Lynn
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Kantoff, Philip
    Konety, Badrinath R
    Murad, Mohammad Hassan
    Penson, David F
    Zietman, Anthony L
    Early detection of prostate cancer: AUA Guideline2013In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 190, no 2, p. 419-426Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    The guideline purpose is to provide the urologist with a framework for the early detection of prostate cancer in asymptomatic average risk men.

    MATERIALS AND METHODS:

    A systematic review was conducted and summarized evidence derived from over 300 studies that addressed the predefined outcomes of interest (prostate cancer incidence/mortality, quality of life, diagnostic accuracy and harms of testing). In addition to the quality of evidence, the panel considered values and preferences expressed in a clinical setting (patient-physician dyad) rather than having a public health perspective. Guideline statements were organized by age group in years (age <40; 40 to 54; 55 to 69; ≥ 70).

    RESULTS:

    Except prostate specific antigen-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests. The quality of evidence for the benefits of screening was moderate, and evidence for harm was high for men age 55 to 69 years. For men outside this age range, evidence was lacking for benefit, but the harms of screening, including over diagnosis and overtreatment, remained. Modeled data suggested that a screening interval of two years or more may be preferred to reduce the harms of screening.

    CONCLUSIONS:

    The Panel recommended shared decision-making for men age 55 to 69 years considering PSA-based screening, a target age group for whom benefits may outweigh harms. Outside this age range, PSA-based screening as a routine could not be recommended based on the available evidence.

  • 17. Collins, Justin
    et al.
    Mottrie, Alexander
    Hosseini, Abolfazl
    Challacombe, Benjamin
    Adding, Christofer
    Dasgupta, Prokar
    Artibani, Walter
    Gaston, Richard
    Piechaud, Thierry
    Sooriakumaran, Prasanna
    Pini, Giovannalberto
    Nilsson, Andreas
    Fragkiadis, Evangelos
    Tewari, Ashutosh
    Badani, Ketan
    Gill, Inderbir
    Desai, Mihir
    Patel, Vipul
    Ahlawat, Rajesh
    Murphy, Declan
    Coelho, Rafael
    Rha, Koon
    Gandaglia, Giorgio
    Verhagen, Harko
    Stockholm University, Faculty of Social Sciences, Department of Computer and Systems Sciences.
    Wiklund, Peter
    Live streaming of robotic surgery from leading educational centres enables a global approach to surgical teaching2016In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 195, no 4, p. e116-Article in journal (Refereed)
    Abstract [en]

    Following recently published EAU Policy on Live Surgical Events (LSE's) it is assured that live surgery will be ongoing at conferences in the immediate future. However, the panel reached >80% consensus view that performing at a home institution may be safer. The committee also identified issues with a ‘travelling surgeon’ performing complex surgery in an unfamiliar environment with a surgical team that is not experienced with the intricacies of surgeons techniques. LSE's from home institutions remove or minimize these negative aspects.

  • 18. Dellagrammaticas, D
    et al.
    Bryden, A A
    Collins, G N
    Regression of metastatic transitional cell carcinoma in response to tamoxifen.2001In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 165, no 5, article id 1631Article in journal (Refereed)
  • 19. Donovan, Michael J.
    et al.
    Khan, Faisal M.
    Fernandez, Gerardo
    Mesa-Tejada, Ricardo
    Sapir, Marina
    Zubek, Valentina Bayer
    Powell, Douglas
    Fogarasi, Stephen
    Vengrenyuk, Yevgen
    Teverovskiy, Mikhail
    Segal, Mark R.
    Karnes, R. Jeffrey
    Gaffey, Thomas A.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Hlavcak, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Freedland, Stephen J.
    Vollmer, Robin T.
    Albertsen, Peter
    Costa, Jose
    Cordon-Cardo, Carlos
    Personalized prediction of tumor response and cancer progression on prostate needle biopsy2009In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 182, no 1, p. 125-132Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To our knowledge in patients with prostate cancer there are no available tests except clinical variables to determine the likelihood of disease progression. We developed a patient specific, biology driven tool to predict outcome at diagnosis. We also investigated whether biopsy androgen receptor levels predict a durable response to therapy after secondary treatment. MATERIALS AND METHODS: We evaluated paraffin embedded prostate needle biopsy tissue from 1,027 patients with cT1c-T3 prostate cancer treated with surgery and followed a median of 8 years. Machine learning was done to integrate clinical data with biopsy quantitative biometric features. Multivariate models were constructed to predict disease progression with the C index to estimate performance. RESULTS: In a training set of 686 patients (total of 87 progression events) 3 clinical and 3 biopsy tissue characteristics were identified to predict clinical progression within 8 years after prostatectomy with 78% sensitivity, 69% specificity, a C index of 0.74 and a HR of 5.12. Validation in an independent cohort of 341 patients (total of 44 progression events) yielded 76% sensitivity, 64% specificity, a C index of 0.73 and a HR of 3.47. Increased androgen receptor in tumor cells in the biopsy highly significantly predicted resistance to therapy, ie androgen ablation with or without salvage radiotherapy, and clinical failure (p <0.0001). CONCLUSIONS: Morphometry reliably classifies Gleason pattern 3 tumors. When combined with biomarker data, it adds to the hematoxylin and eosin analysis, and prostate specific antigen values currently used to assess outcome at diagnosis. Biopsy androgen receptor levels predict the likelihood of a response to therapy after recurrence and may guide future treatment decisions.

  • 20.
    Drake, Marcus J
    et al.
    Tyne Micturution Research Group, School of Surgical Sciences, University of Newcastle, United Kingdom..
    Hedlund, Petter
    Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden.
    Andersson, Karl-Erik
    Department of Clinical Pharmacology, University of Lund, Sweden..
    Brading, Alison F
    Hussain, Iqbal
    Fowler, Clare
    Landon, David N
    Morphology, phenotype and ultrastructure of fibroblastic cells from normal and neuropathic human detrusor: absence of myofibroblast characteristics.2003In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 169, no 4, p. 1573-6Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Fibroblasts are functionally diverse and fibroblastic cells with smooth muscle-like characteristics (myofibroblasts) regulate smooth muscle activity in certain tissues. The presence of myofibroblasts has been reported in the bladder with important implications for normal function and detrusor overactivity. We assessed fibroblastic cell characteristics to discern features suggesting a myofibroblast phenotype in normal or neuropathic human detrusor.

    MATERIALS AND METHODS: A total of 25 control samples were obtained from cadaveric organ donors or patients with a mean age of 42.3 years investigated for hematuria and compared with samples from 18 patients with a mean age of 37.4 years with neurogenic detrusor overactivity. Morphology, phenotypic expression of various markers and the ultrastructure of each fibroblastic cell visible in multiple sections from each specimen was evaluated by 2 independent assessors.

    RESULTS: Fibroblastic cells were observed throughout the smooth muscle and connective tissue. They were located peripherally on muscle fascicles and had a polar stellate appearance with processes ramifying in interfascicular planes and muscle. They possessed vimentin-like immunoreactivity and weak c-kit-like immunoreactivity but not desmin or alpha-smooth muscle actin-like immunoreactivity. Ultrastructurally they showed dilated rough endoplasmic reticulum with a moderately electron dense amorphous content and prominent golgi complexes. Nuclei had clumped peripheral heterochromatin. There were extensive flattened processes that lacked basal laminae. There was no specific contact with nerve fibers or smooth muscle. Neuropathic bladder samples did not differ overtly from those of controls.

    CONCLUSIONS: The detrusor possesses an extensive network of fibroblastic cells and processes. No evidence of myofibroblast differentiation was discerned in normal or neuropathic detrusor, although a minority subpopulation or regional variability in cellular phenotype could not be excluded.

  • 21.
    Drake, Marcus J
    et al.
    Urophysiology Research Group , School of Surgical Sciences, University of Newcastle, United Kingdom.
    Hedlund, Petter
    Department of Clinical Pharmacology, Lund University Hospital, Sweden.
    Harvey, Ian J
    Urophysiology Research Group , School of Surgical Sciences, University of Newcastle, United Kingdom.
    Pandita, Raj Kumar
    Department of Clinical Pharmacology, Lund University Hospital, Sweden.
    Andersson, Karl-Erik
    Department of Clinical Pharmacology, Lund University Hospital, Sweden.
    Gillespie, James I
    Urophysiology Research Group , School of Surgical Sciences, University of Newcastle, United Kingdom.
    Partial outlet obstruction enhances modular autonomous activity in the isolated rat bladder.2003In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 170, no 1, p. 276-279Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Autonomous bladder activity can take the form of localized micromotions (MMs), suggesting that the detrusor may be arranged into component modules, of which each is capable of contracting autonomously. We examined MMs in isolated whole rat bladder and the effects of partial bladder outlet obstruction as a model of detrusor overactivity (DO) to ascertain whether altered modular activity could be an etiological factor in DO.

    MATERIALS AND METHODS: A total of 12 adult female Sprague-Dawley rats underwent obstruction or sham operation for 1 or 4 weeks. Bladders were microsurgically removed and mounted in whole organ tissue baths. Recordings of intravesical pressure and simultaneous registration of intramural contractions were performed under standardized conditions.

    RESULTS: Prior to filling MMs took the form of localized contractions near the vesicoureteral junction in sham operated animals and multifocal microcontractions in obstructed animals. Intravesical volume increases were associated with a change in localized MMs to propagated contraction waves. In sham operated animals stretch resulted in increased MM frequency but decreased amplitude. After obstruction stretch elicited highly coordinated MMs and enhanced intravesical pressure transmission. The time since surgery did not alter observations in the sham or obstructed group.

    CONCLUSIONS: Detrusor muscle in isolated bladders under conditions modeling urine storage may have a functional modular arrangement with the basolateral region most active prior to filling. Peripheral factors determining intravesical pressure include the number of modules active, coordination and intramural tension at other sites. After bladder outlet obstruction more modules are active at baseline and their coordination is enhanced by stretch, leading to increased pressure fluctuations. Such changes may contribute to the development of DO.

  • 22. Elmer, Caroline
    et al.
    Blomgren, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Falconer, Christian
    Zhang, Anju
    Altman, Daniel
    Histological Inflammatory Response to Transvaginal Polypropylene Mesh for Pelvic Reconstructive Surgery2009In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 181, no 3, p. 1189-1195Article in journal (Refereed)
    Abstract [en]

    Purpose: We prospectively evaluated the histological inflammatory response to the large polypropylene transvaginal mesh used for pelvic organ prolapse surgery. Materials and Methods: Ten patients and 8 controls underwent vaginal punch biopsy sampling before surgery and patients also underwent it I year after pelvic reconstructive surgery using polypropylene mesh. Foreign body response to the mesh was assessed using a combination of histological, semiquantitative and computerized image based analysis. Results: Compared to preoperative histology there was a significant postoperative increase in macrophage and mast cell counts (p = 0.03 and 0.01) but no significant changes in the count of cells involved primarily in the infectious cell response or collagen density and the elastin area fraction at the mesh-tissue interface (p = 0.2 and 0.3, respectively). Three cases of mild granuloma formation and 2 of mild erosion were observed. There was no significant change in epithelial thickness when comparing preoperative and postoperative samples. Conclusions: When used for pelvic reconstructive surgery, macroporous monofilament polypropylene mesh induces a mild but persistent foreign body reaction.

  • 23. Frioriksson, Jon Om
    et al.
    Holmberg, Erik
    Adolfsson, Jan
    Lambe, Mats
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Carlsson, Stefan
    Hugosson, Jonas
    Stattin, Par
    Rehospitalization after Radical Prostatectomy in a Nationwide, Population Based Study2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 1, p. 112-119Article in journal (Refereed)
    Abstract [en]

    Purpose: We investigated hospital readmission frequency during the 90 days after radical prostatectomy and assessed the readmission risk associated with potentially related variables. Materials and Methods: Using the population based, nationwide PCBaSe (Prostate Cancer data Base Sweden) we identified men diagnosed with incident prostate cancer between 2000 and 2011 who underwent radical prostatectomy as primary treatment. We used logistic regression analysis to examine the association of the risk of 90-day postoperative readmission with surgical method, calendar period, tumor risk category, hospital case load and patient characteristics. Results: During 90 postoperative days 2,317 of the 24,122 men (10%) identified were nonelectively readmitted, specifically 10% after retropubic, 9% after robot-assisted and 11% after laparoscopic radical prostatectomy. The range in readmission frequency among hospitals was 0% to 35%. Higher readmission risk was associated with the early calendar period (2009 to 2011 vs 2000 to 2002 OR 0.71, 95% CI 0.61-0.83), greater age (70 or greater vs less than 60 years OR 1.17, 95% CI 1.00-1.36), higher risk category (high vs low OR 1.78, 95% CI 1.57-2.03), high comorbidity (Charlson comorbidity index 3 or greater vs 0 OR 1.77, 95% CI 1.29-2.44) and low hospital surgical volume (150 or greater vs fewer than 30 radical prostatectomies per year OR 0.70, 95% CI 0.60-0.81). Conclusions: Readmission rates after different radical prostatectomy methods were similar, ranging from 9% to 11%, with wide variation among hospitals. Readmission rates can be used as an indicator of perioperative care quality but potential confounders must be adjusted to avoid bias.

  • 24.
    Friðriksson, Jón Örn
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Erik
    Adolfsson, Jan
    Lambe, Mats
    Bill-Axelson, Anna
    Carlsson, Stefan
    Hugosson, Jonas
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Rehospitalization after radical prostatectomy in a nationwide, population-based study2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 1, p. 112-119Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate readmission frequencies during the 90 days following radical prostatectomy and to assess readmission risk associated with potentially related variables.

    MATERIALS AND METHODS: Using the population-based, nationwide database Prostate Cancer data Base Sweden (PCBaSe), we identified men diagnosed with incident prostate cancer between 2000 and 2011 who underwent radical prostatectomy (RP) as their primary treatment, and we used logistic regression analysis to examine the association of the risk of 90-day postoperative readmission with surgical method, calendar period, tumor risk category, hospital case load, and patient characteristics.

    RESULTS: During the 90 postoperative days, 2,317 (10%) of the 24,122 men identified were non-electively readmitted, specifically 10% after retropubic radical prostatectomy (RRP), 9% after robot-assisted RP (RALP) and 11% after laparoscopic RP (LRP). The range in the readmission frequency between hospitals was 0-35%. A higher risk of readmission was associated with early calendar period (2009-2011 vs. 2000-2002: odds ratio (OR), 0.71; 95% confidence interval (CI), 0.61-0.83), greater age (≥70 years vs. <60 years: OR, 1.17; 95% CI, 1.00-1.36), higher risk category (high vs. low-risk category: OR, 1.78; 95% CI, 1.57-2.03), high comorbidity (Charlson comorbidity index ≥3 vs. 0: OR, 1.77; 95% CI, 1.29-2.44), and low hospital surgical volume (≥150 vs. <30 RPs per year: OR, 0.70; 95% CI, 0.60-0.81).

    CONCLUSIONS: Readmission rates after different RP methods were similar, ranging from 9% to 11%, with a wide variation between hospitals. Readmission rates can be used as an indicator of perioperative care quality, but potential confounders need to be adjusted to avoid bias.

  • 25.
    Fuellhase, Claudius
    et al.
    University of Munich, Germany .
    Russo, Andrea
    San Raffaele University, Italy .
    Castiglione, Fabio
    San Raffaele University, Italy .
    Benigni, Fabio
    San Raffaele University, Italy .
    Campeau, Lysanne
    Wake Forest University, NC USA .
    Montorsi, Francesco
    San Raffaele University, Italy .
    Gratzke, Christian
    University of Munich, Germany .
    Bettiga, Arianna
    San Raffaele University, Italy .
    Stief, Christian
    University of Munich, Germany .
    Andersson, Karl-Erik
    Wake Forest University, NC USA .
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Spinal Cord FAAH in Normal Micturition Control and Bladder Overactivity in Awake Rats2013In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 189, no 6, p. 2364-2370Article in journal (Refereed)
    Abstract [en]

    Purpose: We assessed whether spinal inhibition of the cannabinoid degrading enzyme FAAH would have urodynamic effects in normal rats and rats with bladder overactivity induced by partial urethral obstruction or prostaglandin E2. We also determined the expression of FAAH, and the cannabinoid receptors CB1 and CB2 in the sacral spinal cord. Materials and Methods: We used 44 rats for functional (cystometry) and Western blot experiments. The FAAH inhibitor oleoyl ethyl amide (3 to 300 nmol) was administered intrathecally (subarachnoidally) or intravenously. The expression of FAAH and CB1/CB2 receptors was determined by Western blot. Results: Oleoyl ethyl amide given intrathecally affected micturition in normal rats and rats with bladder overactivity but effects were more pronounced in the latter. In normal rats oleoyl ethyl amide only decreased micturition frequency, while it decreased frequency and bladder pressures in rats with bladder overactivity. Intravenous oleoyl ethyl amide (3 to 300 nmol) had no urodynamic effect. FAAH and CB1/CB2 receptors were expressed in the rat sacral spinal cord. The expression of CB1/CB2 receptors but not FAAH was higher in obstructed than in normal rats. Conclusions: FAAH inhibition in the sacral spinal cord by oleoyl ethyl amide resulted in urodynamic effects in normal rats and rats with bladder overactivity. The spinal endocannabinoid system may be involved in normal micturition control and it appears altered when there is bladder overactivity.

  • 26. Geirsson, Gudmundur
    et al.
    Lindström, Sivert
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Fall, Magnus
    The bladder cooling reflex and the use of cooling as stimulus to the lower urinary tract.1999In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 162, p. 1890-1896Article in journal (Refereed)
  • 27.
    Gladh, Gunilla
    et al.
    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.
    Outcome of the bladder cooling test in children with neurogenic bladder dysfunction1999In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 161, no 1, p. 254-258Article in journal (Refereed)
    Abstract [en]

    Purpose

    We evaluated the diagnostic use of the bladder cooling test in children with neurogenic bladder dysfunction.

    Materials and Methods

    We performed 201 bladder cooling tests in 65 female and 43 male patients 5 days to 17 years old, including 70 with myelomeningocele, 12 with high spinal lesions, 9 with sacral spinal lesions and 17 with encephalopathy of various types. At the end of routine cystometry we rapidly infused body temperature saline to approximately a third of cystometric capacity, followed by the same volume of saline at 4 to 8C. The test was considered positive when a detrusor contraction greater than 30 cm. water was evoked by the cold but not the warm infusion.

    Results

    The bladder cooling test was positive in 37 children younger than 4 years, at which age it is normally positive. The test was negative in only 2 patients, indicating a complete lower motor neuron lesion. It was positive in 34 of the 57 children older than 6 years, at which age it should be negative. Thus, the positive bladder cooling test confirmed neurogenic bladder dysfunction. Four of the 20 children with a negative test voided normally, while the remainder had no voiding contractions, suggesting a nonfunctional spinal sacral reflex arch to the bladder.

    Conclusions

    The bladder cooling test is a simple, reliable assessment that may serve to demonstrate a functional sacral reflex arch in young patients without voiding contractions or confirm a suspected lower motor neuron lesion. It may be used longitudinally to demonstrate changes in bladder function with growth.

  • 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 Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Outcome of the bladder cooling test in children with nonneurogenic bladder problems2004In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 172, no 3, p. 1095-1098Article in journal (Refereed)
    Abstract [en]

    Purpose:

    The bladder cooling test (BCT) engages a primitive neonatal spinal reflex that becomes suppressed by descending signals in older children and may reappear with suprasacral lesions. We assessed the outcome of the BCT in a large group of children with nonneurogenic bladder problems.

    Materials and Methods:

    The BCT was evaluated in a consecutive series of 178 girls and 106 boys, 1 month to 18 years old with bladder problems without overt neurology. The test was performed at the end of routine cystometry by a rapid control infusion of body warm saline followed, after fluid evacuation, by the same volume of cold saline (3 to 10C). The test was considered positive if a detrusor contraction greater than 30 cm H2O was evoked by the cold but not the warm fluid.

    Results:

    Most children younger than 4 years had a history of pyelonephritis (29 of 34) and/or had vesicoureteral reflux (grade IV to V in 26 of 34). For those younger than 2 years 87% of the BCTs were positive while only 21% of the tests were positive in 2 to 3-year-old children. Most children older than 4 years had idiopathic urge incontinence, and greater than 50% of the BCTs were positive in the youngest (less than 6 years) with a gradual decline to 0% at age 13 years.

    Conclusions:

    Conversion of positive to negative BCTs at about age 2 years presumably represents normal maturation while positive tests in older incontinent children suggest delayed maturation of the central neuronal control of the bladder.

  • 29.
    Gomez-Pinilla, Pedro J
    et al.
    - Spanien.
    Gomez, Maria F
    Lund.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Swärd, Karl
    Lund.
    Hellstrand, Per
    Lund.
    Camell, Pedro J
    Spanien.
    Pozo, Maria J
    Spanien.
    Andersson, Karl-Erik
    Lund/North Carolina.
    Effect of melatonin on age associated changes in guinea pig bladder function2007In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 177, p. 1558-1561Article in journal (Refereed)
    Abstract [en]

    Purpose

    The incidence of urinary incontinence increases with age but the cause and effect relationship between aging and altered bladder function is poorly understood. It was suggested that melatonin can ameliorate negative effects induced by aging by its free radical scavenging activity and its ability to decrease oxidative stress. We investigated the changes in bladder function evoked by aging and the possible benefits of melatonin treatment on age related bladder disturbances.

    Materials and Methods

    Bladder function was assessed using cystometry in conscious, freely moving female guinea pigs. Animals were grouped according to age as young adults (4 months old) and senescents (18 to 20 months old). A group of senescent animals were treated with 2.5 mg kg−1 day−1 melatonin for 21 days.

    Results

    Aging led to increased detrusor activity, as demonstrated by short micturition intervals, decreased bladder capacity and spontaneous contractions during the filling phase. During the voiding phase aged animals showed lower micturition pressures than young adults. Melatonin counteracted the cystometric changes in senescent animals and restored micturition parameters to those of young adults.

    Conclusions

    These results show that in guinea pigs aging induces detrusor overactivity. Melatonin treatment improved age induced changes in bladder function. If similar effects can be demonstrated in humans, melatonin treatment may be a new approach to decrease the impact of age related bladder disorders.

  • 30.
    Hammar, Mats
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Frisk, Jessica
    Linköping University, Department of health and environment. Linköping University, Faculty of Health Sciences.
    Grimsås, Ö
    Department of Surgery, County Hospital, Ludvika, Sweden.
    Höök, M
    Department of Surgery, County Hospital, Ludvika, Sweden.
    Spetz, Anna-Clara
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Wyon, Yvonne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Acupuncture treatment of vasomotor symptoms in men with prostatic carcinoma: A pilot study1999In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 161, no 3, p. 853-856Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Most men who undergo castration therapy for prostatic carcinoma will have vasomotor symptoms that usually persist for years. Vasomotor symptoms are elicited from the thermoregulatory center, possibly due to a decrease in hypothalamic opioid activity induced by low sex steroid concentrations. Acupuncture treatment in women, which stimulates hypothalamic opioid activity, alleviates vasomotor symptoms. We report on men treated with acupuncture for relief of vasomotor symptoms after castration therapy.

    MATERIALS AND METHODS: We asked 7 men with vasomotor symptoms due to castration therapy to receive acupuncture treatment 30 minutes twice weekly for 2 weeks and once a week for 10 weeks. Effects on flushes were recorded in logbooks.

    RESULTS: Of the 7 men 6 completed at least 10 weeks of acupuncture therapy and all had a substantial decrease in the number of hot flushes (average 70% after 10 weeks). At 3 months after the last treatment the number of flushes was 50% lower than before therapy. Therapy was discontinued after 10 weeks because of a femoral neck fracture in 1 man and after 3 weeks due to severe back pain in 1.

    CONCLUSIONS: Acupuncture may be a therapeutic alternative in men with hot flushes after castration therapy and merits further evaluation.

  • 31.
    Hannan, Johanna L.
    et al.
    The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
    Albersen, Maarten
    Urological Research Institute, San Raffaele Hospital, Vita-Salute University, Milan, Italy.
    Kutlu, Omer
    The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
    Gratzke, Christian
    Department of Urology, Ludwig-Maximilians-University, Munich, Germany.
    Stief, Christian G.
    Department of Urology, Ludwig-Maximilians-University, Munich, Germany.
    Burnett, Arthur L.
    The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
    Lysiak, Jeffrey J.
    Department of Urology, University of Virginia, Charlottesville, Virginia, USA.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Bivalacqua, Trinity J.
    The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
    Inhibition of Rho-Kinase Improves Erectile Function, Increases Nitric Oxide Signaling and Decreases Penile Apoptosis in a Rat Model of Cavernous Nerve Injury2013In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 189, no 3, p. 1155-1161Article in journal (Refereed)
    Abstract [en]

    Purpose: Bilateral cavernous nerve injury results in up-regulation of ROCK signaling in the penis. This is linked to erectile dysfunction in an animal model of post-prostatectomy erectile dysfunction. We evaluated whether daily treatment with the ROCK inhibitor Y-27632 (Tocris Bioscience, Ellisville, Missouri) would prevent erectile dysfunction in a rat model of bilateral cavernous nerve injury.Materials and Methods: Sprague-Dawley(R) rats underwent surgery to create sham (14) or bilateral (27) cavernous nerve injury. In the injury group 13 rats received treatment with Y-27632 (5 mg/kg twice daily) and 14 received vehicle. At 14 days after injury, rats underwent cavernous nerve stimulation to determine erectile function. Penes were assessed for neuronal and nitric oxide synthase membrane-endothelial nitric oxide synthase. ROCK2 was assessed by Western blot. Cyclic guanosine monophosphate was determined by enzyme-linked immunosorbent assay. Cavernous homogenates were tested for ROCK and protein kinase G enzymatic activity. Penile apoptosis was evaluated using the Apostain technique (Alexis, San Diego, California). Data were analyzed on ROCK using ANOVA and the t test.Results: While erectile function was decreased in rats with bilateral cavernous nerve injury, daily administration of Y-27632 improved erectile responses. Injury decreased neuronal and nitric oxide synthase membrane-endothelial nitric oxide synthase but ROCK2 was significantly increased. Y-27632 treatment restored neuronal nitric oxide synthase, nitric oxide synthase membrane-endothelial nitric oxide synthase and cyclic guanosine monophosphate levels, and protein kinase G activity. Treatment significantly decreased ROCK2 protein and ROCK activity. There were significantly fewer apoptotic cells after treatment than in injured controls.Conclusions: These results provide evidence for up-regulation of the RhoA/ROCK signaling pathway with detrimental effects on erectile function after bilateral cavernous nerve injury. ROCK inhibition improved erectile dysfunction associated with bilateral cavernous nerve injury by preserving penile nitric oxide bioavailability and decreasing penile apoptosis.

  • 32.
    Hedlund, Petter
    et al.
    Lund University Hospital.
    Holmquist, F.
    Lund University Hospital.
    Hedlund, H.
    Lund University Hospital.
    Andersson, K. E.
    Lund University Hospital.
    Effects of nicorandil on human isolated corpus cavernosum and cavernous artery1994In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 151, no 4, p. 1107-1113Article in journal (Refereed)
    Abstract [en]

    Nitric oxide (NO) released from nonadrenergic-noncholinergic (NANC) nerves seems to be a principal mediator of the relaxation of penile erectile tissue necessary for erection, and drugs acting by release of NO have been shown to produce erection when injected intracorporeally into impotent patients. By producing hyperpolarization, K+ channel openers are effective in relaxing isolated penile erectile tissue from rabbit and man, and can produce tumescence and erection when injected intracorporeally into animals. Nicorandil is classified as a K+ channel opener, but it also acts as a donor of NO. In the present study, the effects of nicorandil on isolated preparations from human corpus cavernosum (CC) and deep cavernous artery (Acc) were compared with those of cromakalim (K+ channel opener) and SIN-1 (NO donor). Nicorandil produced a concentration-dependent relaxation of CC and Acc preparations. The relaxations obtained at the highest nicorandil concentration used (10(-4) M.) were 75 +/- 3% and 66 +/- 4% in CC preparations contracted by noradrenaline and endothelin-1, respectively. The corresponding effects in Acc preparations were 70 +/- 14% and 73 +/- 5%. Glibenclamide (blocking ATP-dependent K+ channels) significantly reduced the nicorandil-induced relaxation in CC, but not in Acc. Methylene blue (believed to block soluble guanylate cyclase) reduced nicorandil's relaxant effect in CC, although statistical significance was not obtained. NG-nitro-L-arginine 10(-4) M. (NO synthase inhibitor) did not significantly influence the effect of nicorandil on precontracted preparations in either tissue. In CC preparations contracted by electrical field stimulation, nicorandil and cromakalim concentration dependently inhibited the responses. This effect was significantly counteracted by glibenclamide. It is concluded that nicorandil is effective in relaxing human CC chiefly by its K+ channel opening action, and to some extent by its ability to release NO. For nicorandil's relaxing effect on Acc, ATP dependent K+ channels seem to be of limited importance. If effective in impotent patients, the drug may represent a new, interesting approach to the treatment of erectile dysfunction.

  • 33.
    Hedlund, Petter
    et al.
    Departments of Clinical Pharmacology and Pathology, Lund University Hospital, Lund, Sweden.
    Ny, Lars
    Departments of Clinical Pharmacology and Pathology, Lund University Hospital, Lund, Sweden.
    Alm, Per
    Departments of Clinical Pharmacology and Pathology, Lund University Hospital, Lund, Sweden.
    Andersson, Karl-Erik
    Departments of Clinical Pharmacology and Pathology, Lund University Hospital, Lund, Sweden.
    Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase.2000In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 164, no 3 Part 1, p. 868-875Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To characterize the distribution of cholinergic nerves in the human corpus cavernosum (CC) and spongiosum (CS) using antibodies to the vesicular acetylcholine transporter (VAChT), and to compare this distribution to those of other transmitters/mediators or transmitter/mediator generating enzymes (heme oxygenases: HO-1 and HO-2; neuronal and endothelial NO synthases: nNOS and eNOS; vasoactive intestinal polypeptide: VIP; and tyrosine hydroxylase: TH), and to investigate NO- and carbon monoxide (CO)-mediated effects.

    MATERIALS AND METHODS: Immunocytochemistry, confocal laser scanning microscopy, radioimmunoassay, and functional in vitro studies.

    RESULTS: Along strands of smooth muscle in the CC and CS, rich numbers of VAChT-, nNOS-, VIP-, TH-, and very few HO-1-immunoreactive (-IR) nerve fibers were observed. Immunoreactivities for VAChT and nNOS, VAChT and VIP, and nNOS and VIP, were generally found in the same varicose nerve terminals. TH-IR nerve fibers or terminals did not contain immunoreactivities for VAChT, NOS or VIP. In the endothelium lining penile arteries, immunoreactivities for eNOS, HO-1, and HO-2 were detected. Single endothelial cells, lining the sinusoidal walls of the CC and CS, were found also to contain eNOS and HO-immunoreactivities. Noradrenaline (NA)-contracted preparations of CC and CS were relaxed by NO, CO, carbachol and by electrical stimulation of nerves. Inhibition of NO synthesis abolished electrically- and carbachol-induced relaxation. In NA-activated strips, relaxation induced by exogenously applied NO, but not those by CO, were accompanied by increases in intracellular levels of cyclic GMP.

    CONCLUSIONS: VAChT, NOS and VIP are found in the same nerve terminals within the human CC and CS, suggesting that these terminals comprise a distinct population of parasympathetic, cholinergic nerves. Endothelially derived NO and the HO/CO system may have a complementary role in penile erection.

  • 34.
    Hedlund, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Streng, Tomi
    Lund.
    Lee, Tack
    Lund.
    Andersson, Karl-Erik
    Lund/North Carolina.
    Effects of Tolterodine on Afferent Neutransmission in Normal and Resiniferatoxin Treated conscious Rats2007In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 178, p. 326-331Article in journal (Refereed)
    Abstract [en]

    Purpose

    The beneficial effects of antimuscarinics on detrusor overactivity and overactive bladder syndrome are exerted during bladder filling, when there is no parasympathetic outflow from the spinal cord. We tested the hypothesis that, if tolterodine exerts some of its effects on afferent nerves, the functional elimination of C-fiber afferents should affect the actions of the drug on urodynamic parameters.

    Materials and Methods

    The study was performed in normal female Sprague Dawley rats and rats treated with resiniferatoxin to eliminate vanilloid sensitive afferent nerves. Tolterodine was given intravenously to normal and resiniferatoxin treated animals. To test if tolterodine at the doses used affects efferent neurotransmission the drug was given to normal and resiniferatoxin treated animals in which detrusor activity was induced by apomorphine.

    Results

    In resiniferatoxin treated animals (0.3 mg kg−1 subcutaneously) the mean micturition interval and volume, and mean residual volume increased significantly compared to those in controls. Baseline and micturition pressures in control and resiniferatoxin treated animals were similar, whereas threshold pressures were higher in resiniferatoxin treated animals. In controls 10 μg kg−1 tolterodine administered intravenously increased the mean micturition interval, bladder capacity and micturition volume. In resiniferatoxin treated rats 1 and 10 μg kg−1 tolterodine increased the mean micturition interval, bladder capacity and micturition volume. Subcutaneous administration of 100 μg kg−1 apomorphine induced detrusor overactivity in all rats. The AUC of intravesical pressure during the initial 10 minutes from the start of detrusor overactivity showed no difference between normal and resiniferatoxin treated rats with or without tolterodine pretreatment.

    Conclusions

    Tolterodine increased the micturition interval and bladder capacity in controls and in resiniferatoxin treated animals, suggesting that these effects were exerted independently of resiniferatoxin sensitive afferents. Tolterodine did not decrease the contractile effects of apomorphine at the doses used, suggesting that the drug had no effect on efferent neurotransmission during voiding.

    Purpose

    The beneficial effects of antimuscarinics on detrusor overactivity and overactive bladder syndrome are exerted during bladder filling, when there is no parasympathetic outflow from the spinal cord. We tested the hypothesis that, if tolterodine exerts some of its effects on afferent nerves, the functional elimination of C-fiber afferents should affect the actions of the drug on urodynamic parameters.

    Materials and Methods

    The study was performed in normal female Sprague Dawley rats and rats treated with resiniferatoxin to eliminate vanilloid sensitive afferent nerves. Tolterodine was given intravenously to normal and resiniferatoxin treated animals. To test if tolterodine at the doses used affects efferent neurotransmission the drug was given to normal and resiniferatoxin treated animals in which detrusor activity was induced by apomorphine.

    Results

    In resiniferatoxin treated animals (0.3 mg kg−1 subcutaneously) the mean micturition interval and volume, and mean residual volume increased significantly compared to those in controls. Baseline and micturition pressures in control and resiniferatoxin treated animals were similar, whereas threshold pressures were higher in resiniferatoxin treated animals. In controls 10 μg kg−1 tolterodine administered intravenously increased the mean micturition interval, bladder capacity and micturition volume. In resiniferatoxin treated rats 1 and 10 μg kg−1 tolterodine increased the mean micturition interval, bladder capacity and micturition volume. Subcutaneous administration of 100 μg kg−1 apomorphine induced detrusor overactivity in all rats. The AUC of intravesical pressure during the initial 10 minutes from the start of detrusor overactivity showed no difference between normal and resiniferatoxin treated rats with or without tolterodine pretreatment.

    Conclusions

    Tolterodine increased the micturition interval and bladder capacity in controls and in resiniferatoxin treated animals, suggesting that these effects were exerted independently of resiniferatoxin sensitive afferents. Tolterodine did not decrease the contractile effects of apomorphine at the doses used, suggesting that the drug had no effect on efferent neurotransmission during voiding.

  • 35.
    Hemdan, Tammer
    et al.
    University Hospital Uppsala, Sweden.
    Johansson, Robert
    Umeå University 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.
    Hellström, Pekka
    University Central Hospital, Oulu, Finland.
    Tasdemir, Ilker
    Central Hospital of Rogaland, Stavanger, Norway.
    Malmström, Per-Uno
    University Hospital Uppsala, Sweden.
    5-Year Outcome of a Randomized Prospective Study Comparing bacillus Calmette-Guerin with Epirubicin and Interferon-alpha 2b in Patients with T1 Bladder Cancer2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, no 5, p. 1244-1249Article in journal (Refereed)
    Abstract [en]

    Purpose: In a multicenter, prospectively randomized study we evaluated the 5-year outcomes of bacillus Calmette-Guerin alone compared to a combination of epirubicin and interferon-alpha 2b in the treatment of patients with T1 bladder cancer. Materials and Methods: Transurethral resection was followed by a second resection and bladder mapping. Stratification was for grade and carcinoma in situ. Followup entailed regular cystoscopy and cytology during the first 5 years. The end points assessed in this analysis were recurrence-free survival, time to treatment failure and progression, cancer specific survival and prognostic factors. Results: The study recruited 250 eligible patients. The 5-year recurrence-free survival rate was 38% in the combination arm and 59% in the bacillus Calmette-Guerin arm (p = 0.001). The corresponding rates for the other end points were not significantly different, as free of progression 78% and 77%, treatment failure 75% and 75%, and cancer specific survival 90% and 92%, respectively. The type of treatment, tumor size and tumor status at second resection were independent variables associated with recurrence. Concomitant carcinoma in situ was not predictive of failure of bacillus Calmette-Guerin therapy. An independent factor for treatment failure was remaining T1 stage at second resection. Conclusions: Bacillus Calmette-Guerin was more effective than the tested combination therapy. The currently recommended management with second resection and 3-week maintenance bacillus Calmette-Guerin entails a low risk of cancer specific death. More aggressive treatment in patients with infiltrative tumors at second resection might improve these results. In particular, concomitant carcinoma in situ was not a predictive factor for poor outcome after bacillus Calmette-Guerin therapy.

  • 36.
    Hemdan, Tammer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Johansson, Robert
    Jahnson, Staffan
    Hellström, Pekka
    Tasdemir, Ilker
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Five year outcome of a randomized prospective study comparing bacillus Calmette-Guerin with epirubicin and interferon α 2b in patients with T1 bladder cancer2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, no 5, p. 1244-1249Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

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

    MATERIAL AND METHODS:

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

    RESULTS:

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

    CONCLUSIONS:

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

  • 37.
    Hemdan, Tammer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Jahnson, Staffan
    Segersten, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Emmprin Expression Predicts Response and Survival following Cisplatin Containing Chemotherapy for Bladder Cancer: A Validation Study.2015In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, no 6, p. 1575-1581Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 38.
    Hemdan, Tammer
    et al.
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Malmström, Per-Uno
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Department of Surgical Sciences, Uppsala University, Uppsala.
    Segersten, Ulrika
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Emmprin expression predicts response and survival following cisplatin containing chemotherapy for bladder cancer: A validation study2015In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, no 6, p. 1575-1581Article in journal (Refereed)
    Abstract [en]

    Purpose Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response. Materials and Methods Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry. Results Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p <0.001). The values for cancer specific survival were 76% and 56%, respectively (p <0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p = 0.23) or cancer specific survival (55% vs 51%, p = 0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials. Conclusions Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression. © 2015 American Urological Association Education and Research, Inc.

  • 39.
    Holmdahl, Gundela
    et al.
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Brandström, Per
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sillén, Ulla
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Stokland, Eira
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Jodal, Ulf
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Hansson, Sverker
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    The Swedish reflux trial in children: II. Vesicoureteral reflux outcome2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, no 1, p. 280-285Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We compared reflux status in children with dilating vesicoureteral reflux treated in 3 groups, including low dose antibiotic prophylaxis, endoscopic therapy and a surveillance group on antibiotic treatment only for febrile urinary tract infection.

    MATERIALS AND METHODS: A total of 203 children 1 to younger than 2 years with grade III-IV reflux were recruited into this open, randomized, controlled trial. Endoscopic treatment was done with dextranomer/hyaluronic acid copolymer. The main end point was reflux status after 2 years. Data were analyzed by the intent to treat principle.

    RESULTS: Reflux status improved in all 3 treatment arms. Of patients in the prophylaxis, endoscopic and surveillance groups 39%, 71% and 47%, respectively, had reflux resolution or downgrading to grade I-II after 2 years. This was significantly more common in the endoscopic than in the prophylaxis and surveillance groups (p = 0.0002 and 0.0030, respectively). After 1 or 2 injections 86% of patients in the endoscopic group had no or grade I-II reflux but recurrent dilating reflux was seen in 20% after 2 years.

    CONCLUSIONS: Endoscopic treatment resulted in dilating reflux resolution or downgrading in most treated children. After 2 years endoscopic treatment results were significantly better than the spontaneous resolution rate or downgrading in the prophylaxis and surveillance groups. However, of concern is the common reappearance of dilating reflux after 2 years.

  • 40.
    Holmström, Benny
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Erik
    Egevad, Lars
    Adolfsson, Jan
    Johansson, Jan-Erik
    Hugosson, Jonas
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Outcome of primary versus deferred radical prostatectomy in the National Prostate Cancer Register of Sweden follow-up study2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, no 4, p. 1322-1327Article in journal (Refereed)
    Abstract [en]

    Purpose We assessed outcomes in terms of adverse pathology and prostate cancer specific mortality in men who underwent primary or deferred radical prostatectomy.

    Materials and Methods In the National Prostate Cancer Register of Sweden Follow-Up Study men 70 years old or younger at diagnosis with localized low to intermediate risk prostate cancer diagnosed from 1997 to 2002 were identified. Outcome in terms of adverse pathology, namely upgrading of Gleason score, positive surgical margins and extraprostatic extension, as well as prostate cancer specific mortality, was assessed in 2,344 men who underwent primary radical prostatectomy and 222 who underwent deferred radical prostatectomy after an initial period of surveillance.

    Results Upgrading of Gleason score in surgical specimens vs core biopsies was less frequent after primary (25%) vs deferred radical prostatectomy (38%), p <0.001. There was no significant difference in the percentage of men who underwent primary vs deferred radical prostatectomy for positive surgical margins (33% vs 24%) or extraprostatic extension (27% vs 25%), and there was no difference in any 1 or more of the 3 adverse pathology features (55% vs 56%). After a median followup of 8 years 0.7% of men in the primary radical prostatectomy group and 0.9% in the deferred radical prostatectomy group had died of prostate cancer.

    Conclusions There was no significant difference in the presence of any 1 or more adverse pathology features or in prostate cancer specific mortality after primary compared to deferred radical prostatectomy. However, longer followup is needed to conclusively evaluate the role of deferred radical prostatectomy.

  • 41.
    Häggström, S
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lissbrant, I F
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    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.
    Testosterone induces vascular endothelial growth factor synthesis in the ventral prostate in castrated rats.1999In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 161, no 5, p. 1620-5Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Recent studies suggest that the vasculature is important for the control of prostate growth. Castration induces an involution of the prostate gland and its vasculature. Replacement of testosterone stimulates endothelial cell proliferation and normalizes vascular volumes and blood flow several days before organ regrowth. Antiangiogenesis treatment inhibits the growth of prostate tumors. Understanding the regulation of the prostate vasculature may therefore provide important knowledge of the mechanisms responsible for the growth of non-malignant and malignant prostate tissue. Castration induced regression and testosterone stimulated regrowth of the prostatic vasculature have here been used to study the involvement of the angiogenic factor vascular endothelial growth factor (VEGF) and its receptors flt-1 and flk-1/KDR in the regulation of the prostatic vasculature.

    MATERIALS AND METHODS: VEGF, flt-1, and flk-1/KDR levels were quantified in the rat ventral prostate following castration and testosterone replacement. Methods used were competitive RT-PCR, Western blot and immunohistochemistry.

    RESULTS: VEGF mRNA and protein levels were significantly decreased by castration and testosterone treatment induced VEGF synthesis in the rat ventral prostate epithelium. Flt-1 and flk-1/KDR receptor levels were unaffected by castration and testosterone treatment.

    CONCLUSIONS: Castration down regulates VEGF and testosterone induces VEGF synthesis in epithelial cells in the rat ventral prostate.

  • 42.
    Jacobsen, Jan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Rasmuson, Torgny
    Grankvist, Kjell
    Ljungberg, Börje
    Vascular endothelial growth factor as prognostic factor in renal cell carcinoma2000In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Journal of Urology, Vol. 163, no 1, p. 343-347Article in journal (Refereed)
  • 43.
    Jahnson, Staffan
    et al.
    Department of Urology, Örebro Medical Centre, Örebro, Sweden.
    Karlsson, Mats G.
    Department of Pathology, Örebro Medical Centre, Örebro, Sweden.
    Predictive value of p53 and pRb immunostaining in locally advanced bladder cancer treated with cystectomy1998In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 160, no 4, p. 1291-1296Article in journal (Refereed)
    Abstract [en]

    Purpose: We elucidate the association between altered immunostaining for retinoblastoma gene protein (pRb) and p53 nuclear proteins, and cancer specific death in patients treated with cystectomy for locally advanced bladder cancer.

    Materials and Methods: The hospital records of 173 patients treated with cystectomy for advanced urothelial bladder cancer between 1967 and 1992 were retrospectively reviewed. Representative biopsies obtained before treatment were sectioned and stained using the standard immunohistochemical technique with antibody DO-7 (p53) and antibody PMG3-245 (pRb). A tumor was considered to have an altered p53 expression if 20% or more of tumor cells exhibited nuclear staining. Similarly, if no tumor cell had nuclear immunostaining the tumor was considered to have an altered pRb expression.

    Results: An altered expression was observed for p53 in 98 tumors (57%) and for pRb in 60 (35%). In a proportional hazards analysis no association was found between an altered expression of pRb or p53 and cancer specific death. This finding was also true in another analysis when the results of immunostaining for pRb and p53 were combined.

    Conclusions: An altered expression for pRb and/or p53 was not correlated to cancer specific death. Thus, these parameters could not be used as predictors of treatment outcome after cystectomy for locally advanced bladder cancer.

  • 44.
    Jahnson, Staffan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Sandblom, Dag
    Orebro University Hospital.
    Holmang, Sten
    Sahlgrens University Hospital.
    A Randomized Trial Comparing 2 Doses of Polidocanol Sclerotherapy for Hydrocele or Spermatocele2011In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 186, no 4, p. 1319-1323Article in journal (Refereed)
    Abstract [en]

    Purpose: Polidocanol sclerotherapy for hydrocele or spermatocele combines high efficiency with low morbidity, but the optimal dose is not known. We compared the efficacy and morbidity of 2 or 4 ml polidocanol sclerotherapy for hydrocele or spermatocele. less thanbrgreater than less thanbrgreater thanMaterials and Methods: From 1993 to 2005 a double-blind randomized clinical trial was conducted using 2 or 4 ml polidocanol (30 mg/ml) for sclerotherapy of hydrocele/spermatocele in 224 evaluable patients at 3 university hospitals. Fluid was evacuated and 2 or 4 ml polidocanol was administered by a nurse, with the amount injected concealed from others present. At 3-month followup morbidity was ascertained using a questionnaire completed by the patients. Fluid recurrence was determined clinically and generally re-treated. less thanbrgreater than less thanbrgreater thanResults: After the first treatment, cure was observed in 59% and 47% in the 4 and the 2 ml group, respectively (p = 0.04). More patients in the 4 ml group had complications (31% vs 18%, p = 0.04). Complications were mostly of low or moderate intensity and seldom required medication. After 1 to 4 treatments 200 of 224 patients (89%) were cured and another 10 (5%) had small amounts of residual fluid, with no difference between the groups. Of the patients with hydroceles/spermatoceles larger than 175 ml, 58% and 34% were cured after the first treatment in the 4 and 2 ml groups, respectively (p = 0.012), with no differences in complications between the groups. less thanbrgreater than less thanbrgreater thanConclusions: Polidocanol sclerotherapy was effective for the treatment of hydrocele or spermatocele in our patients, with 94% satisfactory results after 1 to 4 treatments. A dose of 4 ml was superior to 2 ml, particularly for larger hydroceles/spermatoceles.

  • 45. Kruse, Robert
    et al.
    Säve, Susanne
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Persson, Katarina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Adenosine Triphosphate Induced P2Y(2) Receptor Activation Induces Proinflammatory Cytokine Release in Uroepithelial Cells.2012In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 188, no 6, p. 2419-2425Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We characterized and identified the uroepithelial P2 receptor responsible for adenosine triphosphate mediated release of the cytokines interleukin-8 and 6.

    MATERIALS AND METHODS: The human renal epithelial cell line A498 (ATCC™) was cultured and stimulated with different purinergic agonists with or without prior inhibition with different antagonists or signaling pathway inhibitors. Supernatant was analyzed for interleukin-8 and 6 by enzyme-linked immunosorbent assay. P2 receptor mRNA expression was assessed by real-time reverse transcriptase-polymerase chain reaction. The candidate receptor was knocked down with siRNA technology. Interleukin-8 and 6 responses were measured after purinergic stimulation of knocked down cells.

    RESULTS: ATP and ATP-γ-S (Roche Diagnostics, Mannheim, Germany) were equipotent as inducers of interleukin-8 and 6 release. Agonist profile experiments using different P2 receptor agonists indicated that P2Y(2) was the main contributor to this release, although P2Y(11) and P2X(7) activation could not be excluded. Signaling pathway experiments showed that interleukin-8 release involved phospholipase C and inositol trisphosphate mediated signaling, indicating a P2Y receptor subtype. Antagonist experiments indicated P2Y(2) as the responsible receptor. Gene expression analysis of P2 receptors showed that strong expression of P2Y(2) receptor and subsequent knockdown of P2Y(2) receptor mRNA for 72 and 96 hours abrogated interleukin-8 and 6 release after purinergic stimulation with adenosine triphosphate-γ-S.

    CONCLUSIONS: Interleukin-8 and 6 release after purinergic stimulation in uroepithelial A498 cells is mediated through P2Y(2) receptor activation.

  • 46.
    Kruse, Robert
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Säve, Susanne
    School of Health and Medical Sciences, Clinical Research Center (KFC), Örebro University Hospital, Örebro, Sweden; School of Natural Sciences, Linnaeus University (SS), Kalmar, Sweden.
    Persson, Katarina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. School of Health and Medical Sciences, Clinical Research Center (KFC), Örebro University Hospital, Örebro, Sweden; School of Natural Sciences, Linnaeus University (SS), Kalmar, Sweden.
    Adenosine triphosphate induced P2Y(2) receptor activation induces proinflammatory cytokine release in uroepithelial cells2012In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 188, no 6, p. 2419-2425Article in journal (Refereed)
    Abstract [en]

    Purpose: We characterized and identified the uroepithelial P2 receptor responsible for adenosine triphosphate mediated release of the cytokines interleukin-8 and 6.

    Materials and Methods: The human renal epithelial cell line A498 (ATCC™) was cultured and stimulated with different purinergic agonists with or without prior inhibition with different antagonists or signaling pathway inhibitors. Supernatant was analyzed for interleukin-8 and 6 by enzyme-linked immunosorbent assay. P2 receptor mRNA expression was assessed by real-time reverse transcriptase-polymerase chain reaction. The candidate receptor was knocked down with siRNA technology. Interleukin-8 and 6 responses were measured after purinergic stimulation of knocked down cells.

    Results: ATP and ATP-γ-S (Roche Diagnostics, Mannheim, Germany) were equipotent as inducers of interleukin-8 and 6 release. Agonist profile experiments using different P2 receptor agonists indicated that P2Y(2) was the main contributor to this release, although P2Y(11) and P2X(7) activation could not be excluded. Signaling pathway experiments showed that interleukin-8 release involved phospholipase C and inositol trisphosphate mediated signaling, indicating a P2Y receptor subtype. Antagonist experiments indicated P2Y(2) as the responsible receptor. Gene expression analysis of P2 receptors showed that strong expression of P2Y(2) receptor and subsequent knockdown of P2Y(2) receptor mRNA for 72 and 96 hours abrogated interleukin-8 and 6 release after purinergic stimulation with adenosine triphosphate-γ-S.

    Conclusions: Interleukin-8 and 6 release after purinergic stimulation in uroepithelial A498 cells is mediated through P2Y(2) receptor activation.

  • 47. Laven, Brett A.
    et al.
    Orsini, Nicola
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Gerber, Glenn S.
    Wolk, Alicja
    Birth weight, abdominal obesity and the risk of lower urinary tract symptoms in a population based study of Swedish men2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 5, p. 1891-1896Article in journal (Refereed)
    Abstract [en]

    Purpose

    Lower urinary tract symptoms and obesity are prominent health problems. Low birth weight increases the adult risk of adiposity and insulin resistance, which may increase sympathetic activity and potentially lower urinary tract symptoms. Results of obesity and lower urinary tract symptoms studies are conflicting, and low birth weight and lower urinary tract symptoms relationships have not been investigated.

    Materials and Methods

    This cross-sectional study examines lower urinary tract symptoms, body measures, activity, birth weight and lifestyle data collected by questionnaire from 1997 to 1998. Overall 27,858 men were analyzed and odds ratios calculated after excluding those with cancer, cerebrovascular accident, diabetes and incomplete information.

    Results

    After adjustment for age, activity level, smoking, alcohol, coffee intake and body mass index, a significant positive association was seen between abdominal obesity (waist-to-hip ratio) and moderate to severe lower urinary tract symptoms. The risks of moderate to severe and severe lower urinary tract symptoms were 22% (95% CI 1.09–1.37) and 28% (95% CI 1.01–1.63) higher, respectively, for the top vs the lowest abdominal obesity quartile. The risk of nocturia (twice or more per night) was 1.16 (95% CI 1.02–1.33) in men in the top compared to the bottom waist-to-hip ratio quartile. Men with low birth weight (less than 2,500 gm) had a 61% (95% CI 1.12–2.30) higher risk of severe lower urinary tract symptoms compared to men with normal birth weight (2,500 to 3,999 gm). Men in the top waist-to-hip ratio quartile who had low birth weight had twice the risk of severe lower urinary tract symptoms (95% CI 1.29–3.02) compared to men with normal birth weight and in the lowest waist-to-hip ratio quartile.

    Conclusions

    Low birth weight and abdominal adiposity are associated with increased risk of moderate to severe lower urinary tract symptoms in adults. Further investigations are needed to determine if decreases in obesity can ameliorate lower urinary tract symptoms.

  • 48.
    Lee, Dawn
    et al.
    BresMed, England.
    Kildegaard Nielsen, Sandy
    BresMed, England.
    van Keep, Marjolijn
    BresMed, Netherlands.
    Andersson, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Ferring Int PharmaScience Centre, Denmark.
    Greene, Damien
    Sunderland Royal Hospital, England.
    Quality of Life Improvement in Patients Treated with Degarelix versus Leuprorelin for Advanced Prostate Cancer2015In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 193, no 3, p. 839-846Article in journal (Refereed)
    Abstract [en]

    Purpose: We used responses to questionnaires included in the CS21 degarelix trial and published mapping algorithms to address the paucity of evidence for health related quality of life in patients with advanced hormone dependent prostate cancer treated with degarelix. Materials and Methods: We measured health related quality of life in 610 patients enrolled in the CS21 trial using SF-12 (R) and EORTC QLQ-C30. Based on responses to these questionnaires we estimated patient utility using 4 published mapping algorithms. Utility was tested for relationships with aspects of the symptom and side effect burden that may be affected by degarelix treatment, that is prostate specific antigen progression and adverse events. Results: Average utility in patients without prostate specific antigen progression or an adverse event was 0.742, similar to previously published utilities for nonprogressed prostate cancer states. Prostate specific antigen progression was associated with a utility decrement of between 0.062 and 0.134 depending on the mapping algorithm used. Of adverse events considered in our analysis musculoskeletal events were associated with the greatest effects on patient utility with a decrement of between 0.029 and 0.086. The 4 mapping algorithms generated similar utility estimates, although values derived from SF-12 were consistently lower than those derived from EORTC QLQ-C30. Conclusions: Prostate specific antigen progression status and the incidence of treatment and disease related adverse events result in significant decrements to patient health related quality of life. By slowing prostate specific antigen progression degarelix may improve patient utility and the health related quality of life burden.

  • 49.
    Lee, Tack
    et al.
    Korea.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Newgreen, Donald
    USA.
    Urodynamic effects of a novel EP, receptor antagonist in normal rats and rats with bladder outlet obstruction2007In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 177, p. 1562-1567Article in journal (Refereed)
    Abstract [en]

    Purpose

    Prostaglandin E2 and its EP1 receptor were suggested as endogenous modulators of bladder function in the normal physiological state and under pathophysiological conditions. We investigated if the new EP1 receptor antagonist PF-2907617-02 would influence the regulation of normal micturition in rats, and if it affects bladder function in animals with partial bladder outlet obstruction.

    Materials and Methods

    The study was performed in normal female Sprague-Dawley rats and in rats with moderate, experimentally induced bladder outlet obstruction 2 weeks in duration. All animals underwent continuous cystometry in the awake state. PF-2907617-02 was given intravenously at doses of 0.1 and 1.0 mg/kg–1 in normal rats, and at 1.0 mg/kg–1 in bladder outlet obstructed animals. In a group of normal rats detrusor overactivity was produced by intravesical instillation of prostaglandin E2.

    Results

    In normal rats PF-2907617-02 (1 mg/kg–1) significantly increased bladder capacity, micturition volume and the micturition interval but it had no effect on other urodynamic parameters. The lower dose of PF-2907617 (0.1 mg/kg–1) showed no effect. Intravesical prostaglandin E2 (50 μM) induced detrusor overactivity. The antagonist significantly decreased the stimulatory effects of prostaglandin E2 at 0.1 and 1.0 mg/kg–1. In obstructed animals PF-2907617-02 significantly increased the micturition interval but not bladder capacity and residual volume. The drug also decreased the frequency and amplitude of nonvoiding contractions.

    Conclusions

    EP1 receptor is involved in initiation of the micturition reflex in normal rats and in animals with bladder outlet obstruction. It may also contribute to the generation of detrusor overactivity after bladder outlet obstruction. Thus, EP1 receptor antagonists may have potential as treatment for detrusor overactivity in humans.

  • 50.
    Lindström, Sivert
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Mazières, Leonor
    Jiang, Chonghe
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Inhibition of the bladder cooling reflex in the awake state: An experimental study in the cat2004In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 172, no 5 I, p. 2051-2053Article in journal (Refereed)
    Abstract [en]

    Purpose: We assessed the bladder cooling reflex in the awake cat. The bladder cooling reflex is consistently observed in anesthetized adult cats but not in awake, neurologically normal humans. This discrepancy could indicate a state dependant control of the reflex or a species difference. This study was designed to differentiate between these alternatives. Materials and Methods: Under ketamine-xylazine 5 animals had an indwelling catheter inserted into the bladder. The cooling reflex was tested by injections of cold saline into the bladder (4C to 8C), lowering its wall temperature to about 30C to 32C. The volume used (5 ml) was subthreshold for the Aδ micturition reflex, as confirmed by control injections of body warm saline. The procedure was repeated with the animals fully awake and it was well tolerated by all of them. Reflex responses were assessed by induced bladder pressures. Results: Typical bladder cooling reflexes with peak pressures greater than 3 kPa were evoked in all cats when in narcotic sleep (group mean ± CI 7.4 ± 3.1 kPa). No such reflexes were elicited when the animals were awake (2.0 ± 1.0 kPa). The difference was significant at the level of individual animals. Conclusions: The bladder cooling reflex is suppressed in adult cats during wakefulness, as in humans. This state dependent control of the bladder cooling reflex adds to its resemblance to the extensor plantar response (Babinski's sign).

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