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  • Carcinoma, Squamous Cell  (13)
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  • 1
    Language: English
    In: European Urology, December 2016, Vol.70(6), pp.1078-1079
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.eururo.2016.08.035 Byline: Chris Protzel, Oliver W. Hakenberg Author Affiliation: Urology Department, University of Rostock, Rostock, Germany
    Keywords: Medicine
    ISSN: 0302-2838
    E-ISSN: 1873-7560
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  • 2
    Language: English
    In: The Journal of Urology, August 2016, Vol.196(2), pp.570-578
    Description: Penile squamous cell carcinoma is a rare but aggressive cancer. Little is known about pivotal events in tumor pathogenesis and metastasis. Lymph node metastasis is the prevailing prognostic factor while clinical detection in patients remains difficult. Our aim was to identify distinct miRNAs that are differentially expressed in metastatic vs nonmetastatic penile carcinoma, which may serve as diagnostic biomarkers for disease progression. TaqMan® arrays and quantitative polymerase chain reaction were applied to analyze miRNA profiles in penile squamous cell carcinoma specimens and glans tissue from 24 patients. The prognostic value of deregulated miRNAs was analyzed using the Kaplan-Meier method. The Spearman test was applied to determine a potential linkage between distinctive miRNAs in individual patients. Loss of miR-1 (p = 0.0048), miR-101 (p = 0.0001) and miR-204 (p = 0.0004) in metastasizing tumors and associated metastases (p = 0.0151, 0.0019 and 0.0003, respectively) distinguished patients with metastatic and nonmetastatic penile squamous cell carcinoma. These 3 miRNAs showed a coherent expression pattern. Consistently, patients with low levels of all 3 miRNAs had worse survival (p = 0.03). We identified a coordinately regulated miRNA target hub that is over expressed in penile squamous cell carcinoma and associated with lymphovascular invasion. Our results provide evidence of a novel multiple miRNA based signature associated with lymph node metastasis and unfavorable prognosis of penile squamous cell carcinoma. The integrated loss of miR-1, miR-101 and miR-204 may predict the formation of metastases in penile cancer at an early stage.
    Keywords: Penile Neoplasms ; Carcinoma, Squamous Cell ; Neoplasm Metastasis ; Micrornas ; Mortality ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 3
    Language: English
    In: European Urology, June 2015, Vol.67(6), pp.e111-e111
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.eururo.2014.12.016 Byline: Oliver W. Hakenberg, Chris Protzel Author Affiliation: Department of Urology, University Hospital Rostock, Rostock, Germany Article History: Accepted 4 December 2014
    Keywords: Medicine
    ISSN: 0302-2838
    E-ISSN: 1873-7560
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  • 4
    Language: English
    In: Urology, November 2017, Vol.109, pp.140-144
    Description: To analyze the recurrence and survival outcomes of glansectomy in patients with penile squamous cell carcinoma. We performed a retrospective review of 410 patients across 5 international tertiary referral centers between 1999 and 2016. All patients had tumors involving the glans penis and underwent glansectomy as primary treatment. The Kaplan-Meier method and log-rank test were used to calculate survival and recurrence. Median follow-up was 42 months (interquartile range [IQR] 29-56). The median age was 64 years (IQR 53-72). Median tumor size was 2.2 cm (IQR 1.5-3.0). A total of 240 patients (58.5%) had pT2 disease, whereas only 43 patients (10.5%) had pT3 or pT4 disease. The majority of the cohort had poorly differentiated tumors (43.7%). Most recurrences were local at 7.6% (31 patients). Only 14 patients (3.4%) had regional recurrence and 9 patients (2.2%) had distant recurrence. When stratified by pathologic stage, tumors that were pT2 or higher were (  〈 .001) and were more likely to be poorly differentiated (  〈 .001). There were no differences in recurrence location among pathologic stages (  = .15). The 1-, 2-, and 5-year recurrence-free survival were 98%, 94%, and 78%, respectively. There were no differences in overall survival when stratified by stage (  = .67). Glansectomy is an oncologically safe treatment modality for squamous cell carcinoma of the glans in appropriately selected invasive tumors.
    Keywords: Medicine
    ISSN: 0090-4295
    E-ISSN: 1527-9995
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  • 5
    Language: English
    In: Virchows Archiv : an international journal of pathology, February 2011, Vol.458(2), pp.221-9
    Description: Alterations in the p16/cyclinD1/Rb and ARF/Mdm2/p53 pathways are frequent events in the pathogenesis of squamous cell carcinomas. Different mechanisms of p16 regulation have been described for penile carcinomas so far. Therefore, expression of p16 and p53 was immunohistochemically detected with monoclonal antibodies in 52 primary invasive penile squamous cell carcinomas. The carcinomas were analyzed for allelic loss (LOH) in p16(INK4A) and p53, as well as for mutations in the p16(INK4A) and the p53 gene. In addition, we examined the promoter status of p16(INK4A) by methylation-specific PCR. The presence of human papilloma virus (HPV) 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Data were compared to clinical data. Concerning p16, 26 (50%) tumors showed positive immunohistochemistry, 32 (62%) tumors showed allelic loss and 22 tumors (42%) showed promoter hypermethylation. All tumors with negative p16 immunohistochemistry showed LOH near the p16(INK4A) locus and/or hypermethylation of the p16(INK4A) promoter. HPV 16 DNA was detected in 17 tumors, ten of them with positive p16 immunostaining. The remaining seven tumors with negative p16 staining showed allelic loss and/or promoter hypermethylation. Evidence of lymph node metastasis was significantly associated with negative p16 immunohistochemistry as well as with combined LOH and promoter hypermethylation (p = 0.003 and p = 0.018, respectively). Allelic loss around p53 was found in 22 tumors (42%), and seven mutations of the p53 gene could be demonstrated in our tumors. No correlations could be found between any p53 alteration and clinical parameters.
    Keywords: Genes, P16 ; Carcinoma, Squamous Cell -- Genetics ; Penile Neoplasms -- Genetics
    ISSN: 09456317
    E-ISSN: 1432-2307
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  • 6
    Language: English
    In: European Urology, January 2015, Vol.67(1), pp.142-150
    Description: Penile cancer has high mortality once metastatic spread has occurred. Local treatment can be mutilating and devastating for the patient. Progress has been made in organ-preserving local treatment, lymph node management, and multimodal treatment of lymphatic metastases, requiring an update of the European Association of Urology guidelines. To provide an evidence-based update of treatment recommendations based on the literature published since 2008. A PubMed search covering the period from August 2008 to November 2013 was performed, and 352 full-text papers were reviewed. Levels of evidence were assessed and recommendations graded. Because there is a lack of controlled trials or large series, the levels of evidence and grades of recommendation are low compared with those for more common diseases. Penile squamous cell carcinoma occurs in distinct histologic variants, some of which are related to human papilloma virus infection; others are not. Primary local treatment should be organ preserving, if possible. There are no outcome differences between local treatment modes in superficial and T1 disease. Management of inguinal lymph nodes is crucial for prognosis. In impalpable nodes, invasive staging should be done depending on the risk factors of the primary tumour. Lymph node metastases should be treated by surgery and adjuvant chemotherapy in N2/N3 disease. Organ preservation has become the standard approach to low-stage penile cancer, whereas in lymphatic disease, it is recognised that multimodal treatment with radical inguinal node surgery and adjuvant chemotherapy improves outcome. Approximately 80% of penile cancer patients of all stages can be cured. With increasing experience in the management of penile cancer, it is recognized that organ-preserving treatment allows for better quality of life and sexual function and should be offered to all patients whenever feasible. Referral to centres with experience is recommended. Penile preservation should be offered as the primary treatment modality to men with localised penile cancer. Conservative surgery may improve quality of life; however, the risk of local recurrence is higher than after radical surgery (eg, partial penectomy). The management of regional lymph nodes is decisive for long-term patient survival.
    Keywords: Penile Cancer ; Squamous Cell Carcinoma ; Lymph Node ; Invasive Disease ; Metastasis ; Surgery ; Laser ; Chemotherapy ; Reconstruction ; Follow-Up ; Quality of Life ; Guidelines ; European Association of Urology ; Medicine
    ISSN: 0302-2838
    E-ISSN: 1873-7560
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  • 7
    Language: English
    In: Deutsches Arzteblatt international, 28 September 2018, Vol.115(39), pp.646-652
    Description: The incidence of penile cancer in Europe lies in the range of 0.9 to 2.1 cases per 100 000 persons per year. Carcinogenesis is associated with human papilloma virus (HPV) infection and with chronic inflammation. This review is based on publications (2010-2017) retrieved by a selective search in PubMed and EMBASE and on the guidelines of the European Association of Urology, the European Society of Medical Oncology, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence (NICE). 95% of cases of penile cancer are accounted for by squamous cell carcinoma, whose numerous subtypes have different clinical courses. Chronic preputial inflammation due to phimosis or lichen sclerosus is often associated with penile cancer. Circumcision lowers the risk of penile cancer (hazard ratio: 0.33). Maximally organ-preserving surgery with safety margins of no more than a few millimeters is the current therapeutic standard, because a local recurrence, if it arises, can still be treated locally with curative intent. Local radiotherapy can be performed in early stages. Lymphogenic metastasis must be treated with radical lymphadenectomy and adjuvant chemotherapy. Patients with clinically unremarkable inguinal lymph nodes nonetheless need invasive lymph node staging because of the high rate of lymphogenic micrometastasis. Penile cancer is curable in all early stages with the appropriate treatment, but its prognosis depends crucially on the proper management of the regional (i.e., inguinal) lymph nodes. In many countries, the treatment of this rare disease entity has been centralized.
    Keywords: Penile Neoplasms -- Diagnosis
    E-ISSN: 1866-0452
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  • 8
    In: Nuklearmedizin, 2018, Vol.57(01)
    In: Nuklearmedizin, 2018, Vol.57(01), pp.26-30
    Description: Aim: Accurate staging of penile cancer requires invasive methods such as sentinel node biopsy or lymphadenectomy (LAD). We assessed the value of [ F]FDG PET/CT for non-invasive nodal staging in penile cancer (PC) patients before inguinal LAD. Patients and methods: 41 consecutive patients with PC (stage pT1 or higher, cN0) received [ F]FDG PET/CT before undergoing bilateral modified or radical inguinal staging LAD. Lymph nodes with a visually increased [ F]FDG uptake were classified as suspicious of lymph node metastases (LNM). Standardized uptake value (SUV) of suspicious inguinal lymph nodes was determined. Results of [ F]FDG PET/CT were correlated with histopathology. Results: In total 623 lymph nodes were resected, in 10 patients LNM were histologically confirmed (14/623 lymph nodes). In patient-based analysis [ F]FDG PET/CT showed a sensitivity and specificity of 80% and 68 %, respectively, a positive predictive value (PPV) of 44 % and a negative predictive value (NPV) of 91 %. In the groin-based analysis, [ F]FDG PET/CT had a sensitivity of 69 %, a specificity of 77 %, a PPV of 36 % and a NPV of 93 %. There was no significant difference in SUV and SUV between true positive and false positive lymph nodes (p = 0.093 and 0.069, respectively). Conclusion: [ F]FDG PET/ CT shows a high NPV in penile cancer patients without clinically evident LNM. However, due to its limited sensitivity (especially with respect to LNM of small size) and specificity (i. e. in the differentiation between (post)inflammatory and metastatic lymph nodes) [ F]FDG PET/CT cannot replace invasive nodal staging.
    Keywords: Penile cancer[ f]fdg pet/ct ; Nodal staging ; Inguinal lymphadenectomy ; Histopathology ; Peniskarzinom[ f]fdg pet/ct ; Lymphknotenstaging ; Inguinale lymphadenektomie ; Histopathologie
    ISSN: 0029-5566
    E-ISSN: 2567-6407
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  • 9
    Language: English
    In: European Urology Focus, July 2018, Vol.4(4), pp.599-607
    Description: For penile cancer (PC) there are no known molecular predictors of lymphatic spread and/or chemoresistance. To identify functional biomarkers that can predict malignant progression and treatment responsiveness. We used four patient-derived PC cell lines and measured invasion and capillary tube formation, chemoresponsiveness, and mRNA and protein expression. Data were further validated in E2F1 transcription factor knockdown and overexpression experiments. We quantified E2F1 transcript levels in a set of nonmetastatic tumours (NM), metastasised primary tumours (PT), and lymph node metastases (M) from 24 patients. E2F1 immunohistochemistry was performed in another set of 13 PC biopsies. Relationships between different parameters were analysed using Student tests. Transcript levels in patient samples were compared using Mann-Whitney tests. Significance was set at 〈 0.05. In cell lines established from lymph node metastases, E2F1 was more abundantly expressed, pRB was inactivated, and CDK2, CDK4, and cyclins D and E were elevated in comparison to cells from primary PC. Overexpression of E2F1 enhanced migratory capacity and lymphatic endothelial tubule formation, while depletion reduced invasiveness and increased chemosensitivity. VEGFR-3 and VEGF-C and mesenchymal markers were upregulated by high E2F1. E2F1 was clearly upregulated in infiltrative and metastatic primary tumours and metastases (NM vs PT, 〈 0.05; NM vs M, 〈 0.0005). E2F1 Quick scores increased from grade I to grade III tumours. A limitation of the study is the small number of patients. E2F1 is a driver of invasion and lymphatic dissemination and promotes chemoresistance. E2F1-related biomarkers might assist in stratifying PC patients for different treatment regimens. The availability of penile cancer cell lines allows molecular research on the mechanisms underlying metastasis and chemotherapy. A critical pathway involved in both features has been identified and may lead to better patient stratification for treatment selection. Functional analyses in cell lines from patients with primary and metastatic penile cancer revealed that E2F1 drives invasiveness, lymphogenic metastasis, and chemoresistance. This allowed identification of prognostic biomarkers that could open up entirely new possibilities in cancer diagnosis and therapy.
    Keywords: Penile Squamous Cell Carcinoma ; E2f1 ; Cancer Invasion ; Chemotherapy ; Lymphangiogenesis ; Experimental Therapeutics ; Medicine
    ISSN: 2405-4569
    E-ISSN: 2405-4569
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  • 10
    Language: English
    In: Urologic Oncology: Seminars and Original Investigations, April 2018, Vol.36(4), pp.147-152
    Description: Although the trend towards penile sparing therapy is increasing for penile squamous cell carcinoma, outcomes for laser ablation therapy have not been widely reported. We assessed the clinical outcomes of penile cancer patients treated with only laser ablation. A retrospective review was performed on 161 patients across 5 multi-center tertiary referral centers from 1985 to 2015. All patients underwent penile sparing surgery with only laser ablation for squamous cell carcinoma of the penis. Laser ablation was performed with neodymium-doped yttrium aluminum garnet or carbon dioxide. Overall and recurrence-free survival was calculated using the Kaplan-Meier method and compared with the log rank test. A total of 161 patients underwent laser ablation for penile cancer. The median age was 62 (IQR: 52–71) years and median follow-up was 57.7 (IQR: 28–90) months. The majority of patients were pTa/Tis (59, 37%) or pT1a (62, 39%). Only 19 (12%) had a poorly differentiated grade. The 5-year recurrence-free survival was 46%. When stratified by stage, the 5-year local recurrence-free survival was pTa/Tis: 50%; pT1a: 41%; pT1b: 38%; and pT2: 52%. The inguinal/pelvic nodal recurrence was pTa/Tis: 2%; pT1a: 5%; pT1b: 18%; and pT2: 22%. There were no differences among stages with respect to recurrence-free survival ( = 0.98) or overall survival ( = 0.20). Laser ablation therapy is safe for appropriately selected patients with penile squamous cell carcinoma. Due to the increased risk of nodal recurrence, laser ablation coupled with diagnostic nodal staging is indicated for patients with pT1b or higher.
    Keywords: Laser Ablation ; Recurrence ; Penile Sparing Surgery ; Penile Squamous Cell Carcinoma ; Medicine
    ISSN: 1078-1439
    E-ISSN: 1873-2496
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