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  • 1.
    Kirrander, Peter
    et al.
    Örebro University Hospital.
    Andrén, Ove
    Örebro University Hospital.
    Windahl, Torgny
    Örebro University Hospital. Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Dynamic sentinel node biopsy in penile cancer: initial experiences at a Swedish referral centre2013In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 111, no 3B, p. E48-E53Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 2.
    Kirrander, Peter
    et al.
    Örebro University Hospital, Örebro, Sweden.
    Kolaric, Aleksandra
    Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Örebro University Hospital, Örebro, Sweden.
    Windahl, Torgny
    Örebro University Hospital, Örebro, Sweden.
    Andrén, Ove
    Örebro University Hospital, Örebro, Sweden.
    Stark, Jennifer Rider
    Örebro University Hospital, Örebro, Sweden; Brigham & Women’s Hospital, Boston MA, USA; Harvard Medical School, Boston MA, USA.
    Lillsunde-Larsson, Gabriella
    Örebro University Hospital, Örebro, Sweden.
    Elgh, Fredrik
    Örebro University, School of Health and Medical Sciences. Umeå University, Umeå, Sweden.
    Karlsson, Mats G.
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Human papillomavirus prevalence, distribution and correlation to histopathological parameters in a large Swedish cohort of men with penile carcinoma2011In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 108, no 3, p. 355-359Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 3.
    Kirrander, Peter
    et al.
    Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Sherif, Amir
    Dept Surg & Perioperat Sci, Urol & Androl, Umeå Univ, Umeå, Sweden.
    Friedrich, Bengt
    Dept Surg & Perioperat Sci, Urol & Androl, Umeå Univ, Umeå, Sweden.
    Lambe, Mats
    Reg Canc Ctr Uppsala Orebro, Uppsala Univ, Uppsala, Sweden; Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
    Håkansson, Ulf
    Dept Urol, Skåne Univ, Malmö, Sweden.
    Swedish National Penile Cancer Register: incidence, tumour characteristics, management and survival2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 2, p. 287-292Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 4.
    Liedberg, Fredrik
    et al.
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Hagberg, Oskar
    Regional Cancer Centre South, Region Skåne, Lund, Sweden.
    Aljabery, Firas
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Hosseini, Abolfazl
    Department of Urology, Karolinska University Hospital, Stockholm, Sweden.
    Jahnson, Staffan
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Jancke, Georg
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Department of Urology.
    Malmström, Per-Uno
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Sherif, Amir
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Ströck, Viveka
    Department of Urology, Sahlgrenska University Hospital and, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Häggström, Christel
    Department of Biobank Research, Umeå University, Umeå, and Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; School of Medicine, King's College, London, UK.
    Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study2019In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 124, no 3, p. 449-456Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the association between hospital volume on overall survival (OS), cancer-specific survival (CSS), and quality of care defined as use of extended lymphadenectomy, continent reconstruction, neoadjuvant chemotherapy and treatment delay less than 3 months.

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

    RESULTS: PSMAV in the highest tertile (25 or more cystectomies annually) was associated with improved overall survival (HR 0.87, 95% CI 0.75-1.0), whereas corresponding HR for cancer-specific survival was 0.87 (95% CI 0.73-1.04). With PSMAV as a continuous variable, overall survival was improved for every increase of 10 cystectomies annually (HR 0.95, 95% CI 0.90-0.99). Moreover, higher PSMAV was associated with increased use of extended lymphadenectomy, continent reconstruction and neoadjuvant chemotherapy, but also more frequently with a treatment delay of more than 3 months after diagnosis.

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

  • 5.
    Sriplakich, S.
    et al.
    Department of Urology, Örebro Medical Centre, Örebro, Sweden .
    Jahnson, S.
    Department of Urology, Örebro Medical Centre, Örebro, Sweden.
    Karlsson, Mats G
    Department of Pathology, Örebro Medical Centre, Örebro, Sweden.
    Epidermal growth factor receptor expression: predictive value for the outcome after cystectomy for bladder cancer?1999In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 83, no 4, p. 498-503Article in journal (Refereed)
    Abstract [en]

    Objective: To determine whether epidermal growth factor receptor (EGFR) immunostaining of tumour cells is associated with cancer-specific death after cystectomy for locally advanced bladder cancer.

    Patients and Methods: The hospital records of all patients treated with cystectomy for urothelial cancer of the urinary bladder between 1967 and 1992 were reviewed retrospectively. The paraffin-embedded specimens obtained before treatment from 173 patients were processed for immunohistochemical staining, using the monoclonal antibody NCL-EGFR (Novocastra, UK). EGFR immunostaining was considered positive if membrane staining was found in at > or = 20% of tumour cells in one or more fields at > or = 200 (area 0.59 mm2).

    Results: Most patients (149) received preoperative irradiation and one had neoadjuvant chemotherapy. The mean observation time was 81.3 months; 63 patients (36%) had tumour recurrence within 1-80 months (mean 18.3). Positive EGFR immunostaining was found in 100 patients (58%). The proportion of T2-4 tumours was higher in those EGFR-positive than in those EGFR-negative. Proportional-hazards analysis revealed that clinical stage was significantly associated with cancer-specific death, but EGFR expression was not.

    Conclusion: Although positive immunostaining for EGFR was more frequent in higher stages of locally advanced bladder cancer, this variable was not an independent predictor of outcome after cystectomy.

  • 6.
    Svensson, Lovisa
    et al.
    Sch Pure & Appl Nat Sci, Univ Kalmar, Kalmar, Sweden.
    Säve, Susanne
    Univ Kalmar, Sch Pure & Appl Nat Sci, Kalmar, Sweden.
    Persson, Katarina
    Örebro University, School of Health and Medical Sciences. Sch Pure & Appl Nat Sci, Univ Kalmar, Kalmar, Sweden.
    The effect of nitric oxide on adherence of P-fimbriated uropathogenic Escherichia coli to human renal epithelial cells2010In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 105, no 12, p. 1726-1731Article in journal (Refereed)
    Abstract [en]

    Objectives: To examine the effect of nitric oxide (NO), an endogenous component of the host defence in urinary tract infection, on the adherence of P-fimbriated uropathogenic Escherichia coli (UPEC) to human renal epithelial cells.

    Materials and Methods: Two wild-type UPEC strains (AD110 and IA2) and the P-fimbriated recombinant strain HB101pPIL-75 were used. Bacteria were allowed to adhere to the human renal epithelial cell line A498 and attachment was evaluated in the absence or presence of the NO donor DETA/NONOate (1 mm). Total RNA was extracted from NO-exposed bacteria in static urine cultures, followed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of the papG gene that encodes the P-fimbriae adhesin PapG.

    Results: Bacterial adherence to A498 cells was fimbriae-dependent and the ability to agglutinate human P-1 positive erythrocytes confirmed that the used strains were P-fimbriated. UPEC strains AD110 and IA2 attached by a mean of 8 bacteria/cell and 20 bacteria/cell, respectively. In the presence of DETA/NONOate, the attachment of AD110 and IA2 to A498 cells was significantly reduced by a mean (sem) of 34 (3.9)% and 45 (14)%, respectively. The expression of papG was decreased after DETA/NONOate exposure as shown by semiquantitative RT-PCR.

    Conclusion: NO disrupted functional adhesion of P-fimbriated UPEC to kidney epithelial cells, suggesting that NO-production from epithelial cells in the urinary tract may limit bacterial colonization at the mucosal surface. The reduced adherence may involve transcriptional effects of NO on papG expression, but further studies are needed to establish the underlying mechanisms.

  • 7. Säve, Susanne
    et al.
    Mjösberg, Jenny
    Poljakovic, Mirjana
    Mohlin, Camilla
    Persson, Katarina
    Örebro University, School of Health and Medical Sciences.
    Adenosine receptor expression in Escherichia coli-infected and cytokine-stimulated human urinary tract epithelial cells2009In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 104, no 11, p. 1758-1765Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the expression and regulation of adenosine receptors in unstimulated, uropathogenic Escherichia coli (UPEC)-infected and cytokine-stimulated human urinary tract epithelial cells, and to examine the regulation of interleukin (IL)-6 secretion in response to A2A receptor activation.

    Materials and methods: Human urinary tract epithelial cells (A498, T24 and RT4) were grown in cell culture and stimulated with a mixture of pro-inflammatory cytokines (CM) or UPEC. The expression of adenosine receptors was evaluated using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunocytochemistry. IL-6 secretion was measured with an enzyme-linked immunosorbent assay.

    Results: RT-PCR analysis showed the presence of transcripts for the A1, A2A and A2B receptor subtypes but not for the A3 receptor in A498 kidney epithelial cells. The expression of A2A receptor mRNA increased in A498 epithelial cells exposed to CM and UPEC, while A1 and A2B receptor transcripts decreased or remained unchanged. Up-regulation of A2A receptors was confirmed at the protein level using Western blot analysis and immunocytochemistry. There was also an increase in A2A receptor mRNA in human bladder epithelial cells (T24 and RT4) and in mouse bladder uroepithelium in response to cytokines and UPEC. IL-6 secretion in UPEC-infected A498 cells was decreased by 38% when exposed to the A2A receptor agonist CGS 21680.

    Conclusion: Our data showed a subtype-selective plasticity among adenosine receptors in urinary tract epithelial cells in response to UPEC-infection and cytokines. There was a consistent up-regulation of A2A receptors in kidney and bladder epithelial cells. Functionally, A2A receptor activation reduced UPEC-induced IL-6 secretion. These findings suggest that adenosine might be a previously unrecognized regulator of the mucosal response in urinary tract infection.

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