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  • 1.
    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.

  • 2.
    Håkansson, Ulf
    et al.
    Dept Urol, Skåne Univ Hosp, Malmö, Sweden.
    Kirrander, Peter
    Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Uvelius, Bengt
    Dept Urol, Skåne Univ Hosp, Malmö, Sweden.
    Baseckas, Gediminas
    Dept Urol, Skåne Univ Hosp, Malmö, Sweden.
    Torbrand, Christian
    Dept Urol, Skåne Univ Hosp, Malmö, Sweden.
    Organ-sparing reconstructive surgery in penile cancer: initial experiences at two Swedish referral centres2015In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, no 2, p. 149-154Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to present early outcome data for patients treated for penile cancer with organ-sparing reconstructive surgery at two referral centres in Sweden.

    Material and methods: Oncological, cosmetic and functional outcome and complications were analysed retrospectively during the period 2011-2013. Twelve patients with non-invasive penile cancer were treated with glans resurfacing (GR), while 15 patients with invasive penile cancer underwent total glansectomy with neoglans reconstruction (TGN).

    Results: The 12 patients treated with GR had a median age of 66 years (range 35-83 years) and a median follow-up time of 16 months (range 4-40 months). All patients showed carcinoma in situ and negative surgical margins in the final pathology report. The 15 patients treated with TGN had a median age of 71 years (range 37-78 years) and the median follow-up time was 10 months (range 1-25 months). All patients had invasive penile cancer and the surgical margins were negative in all cases except one. Complications occurred in five of the 27 patients (18%), and in most cases these were minor and infection related. No recurrences were seen in either group during follow-up, and all patients except one, who had undergone GR, were satisfied with the functional and cosmetic results.

    Conclusions: GR and TGN seem to be oncologically safe procedures for treating carefully selected patients with penile cancer, and the functional and cosmetic results are promising. Based on these findings, the authors recommend that penile amputation should only be carried out in patients who are not suitable for organ-sparing reconstructive surgery.

  • 3.
    Jakobsen, Jakob Kristian
    et al.
    Dept Urol, Aarhus Univ Hosp, Aarhus, Denmark.
    Krarup, Kim Predbjorn
    Dept Urol, Copenhagen Univ Hosp, Copenhagen, Denmark.
    Kirrander, Peter
    Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Håkansson, Ulf
    Dept Urol, Skåne Univ Hosp, Malmö, Sweden.
    Kaipia, Antti
    Dept Surg, Satakunta Cent Hosp, Pori, Finland.
    Perttila, Ilkka
    Dept Urol, Helsinki Univ Hosp, Helsinki, Finland.
    Axcrona, Karol
    Dept Surg, St Olavs Univ Hosp, Trondheim, Norway.
    Torkelsen, Tor Kristian
    Dept Urol, Haukeland Hosp, Bergen, Norway.
    Hilmarsson, Rafn
    Div Surg, Natl Univ Hosp Iceland, Reykjavik, Iceland.
    Jensen, Jorgen Bjerggaard
    Dept Urol, Aarhus Univ Hosp, Aarhus, Denmark.
    Penile cancer in Scandinavia: Current practice and future perspectives2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 1, p. 90-92Article in journal (Refereed)
  • 4.
    Kirrander, Peter
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Penile cancer: studies on prognostic factors2014Doctoral thesis, comprehensive summary (Other academic)
  • 5.
    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.

  • 6.
    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.

  • 7.
    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.

  • 8.
    Leijte, Joost A. P.
    et al.
    The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
    Kirrander, Peter
    Örebro University Hospital.
    Antonini, Ninja
    The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
    Windahl, Torgny
    Örebro University Hospital.
    Horenblas, Simon
    The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
    Recurrence patterns of squamous cell carcinoma of the penis: Recommendations for follow-up based on a two-centre analysis of 700 patients2008In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 54, no 1, p. 161-169Article in journal (Refereed)
    Abstract [en]

    Background: Current follow-up recommendations for patients with penile carcinoma are based on small numbers of patients.

    Objectives: To give further insight into the recurrence patterns of penile carcinoma in different treatment settings and provide recommendations for follow up.

    Designs, Setting, and Participants: In this retrospective study, we analysed 700 patients from two referral centres for penile carcinoma for recurrences.

    Measurements: Recurrences were categorized as local, regional, or distant. The rate of local recurrences was compared between patients undergoing penile-preserving treatments and partial/total amputation. Regional recurrences were compared between patients surgically staged as pN0 or pN+ and clinically node-negative (cN0) patients subjected to a wait-and-see policy. The total recurrence rate, type of recurrence, time to recurrence, and survival were calculated.

    Results and Limitations: 205 out of 700 patients (29.3%) had a recurrence, consisting of 18.6% local, 9.3% regional, and 1.4% distant recurrences. Of the recurrences, 92.2% occurred within 5 yr after primary treatment. All regional and distant recurrences occurred within 50 and 16 mo, respectively. The local recurrence rate was 27.7% after penile-preserving therapy and 5.3% after amputation. The regional recurrence rate was 2.3% in patients staged as pN0, 19.1% in patients staged as pN+, and 9.1% in patients undergoing a wait-and-see policy. The 5-yr disease-specific survival was 92% after a local recurrence and 32.7% after a regional recurrence. All patients with a distant recurrence died within 22 mo. Although the number of analysed patients is substantial, the results do not necessarily reflect those of other centres using different techniques for the management of penile carcinoma.

    Conclusions: Patients undergoing penile-preserving therapy, patients surgically staged as pN+, and those undergoing a wait-and-see policy for the nodal status are at high risk of developing a recurrence. Follow-up recommendations are provided based on the risk and impact on survival of a recurrence.

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