enile cancer is an aggressive squamous cell carcinoma of the skin of the glans or of the inner layer of the prepuce, characterized by invasive growth and early metastatic spread to lymph nodes. While penile cancer is uncommon in Europe, incidence rates are very high in parts of South America and Africa. Since its treatment is often associated with significant cosmetic and functional defects, the disease is of critical importance to the affected men. Early metastatic spread to regional lymph nodes can be life-threatening. It is not uncommon that factors, both from the patient and the treating physician, are causing delays in diagnosis and start of treatment. With penile cancer being a comparatively rare disease, many physicians are unfamiliar with its management. Thus, several countries have centralized the treatment of this rare tumor. Penile cancer is an orphan disease. Due the low numbers of patients, no prospective randomized studies have become available. Most of the available data is from small retrospective studies; larger studies result from retrospective multicenter data collections. Thus, the level Summary Background: 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. Methods: 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). Results: 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. Conclusion: 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.
The BK polyomavirus (BKPyV) has pathogenic relevance especially in immunocompromised patients. No causal therapy has been established yet. Therefore, new therapeutic targets need to be identified in experimental studies. A 3D organotypic cell culture model with primary urothelial cells and fibroblasts was used as infection model. The detection of virus replication was performed with quantitative polymerase chain reaction (qPCR), and immunohistochemistry (IHC) was also used for analysis. Interleukin levels were measured by enzyme‐linked immunosorbent assay (ELISA). Interestingly, the signal transducer and activator of transcription 3 (STAT3) pathway seems to be activated during infection with BKPyV, for example phosphorylated STAT3 is significantly ( P < 0.0001) elevated on day 6 following infection. Therefore, we performed ELISAs for involved interleukins in STAT3 pathway. Interleukin 11 (IL‐11) was significantly ( P = 0.026) elevated at day 9. Subsequently, 3D cultures were treated with IL‐11 neutralizing antibody. At day 9 following infection, the median virus replication rate is 4.4 × 10 6 copies/ml. The difference to replication rate without treatment was significantly lower at day 6 ( P < 0.0001) and at day 9 ( P < 0.0001), respectively. STAT3 pathways seem to be involved during BKPyV infection and need further investigation in experimental studies. A very promising target for treatment might be IL‐11.
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There is a high unmet medical need for alternative antimicrobial treatments and test systems due to the growing rate of antibiotic resistances. A promising approach is the use of CAP. For investigation of antimicrobial efficacy and biocompatibility ex ovo, a shell-less hen's egg test on the chick area vasculosa (HET-CAV) was established. Methods An argon plasma jet (kINPen ® 09) and a DBD (dielectric barrier discharge) plasma source based on low temperature cofired ceramic technology (IlmPlas) were compared. Fertilized hen"s eggs were incubated for 72 h and transferred into petri dishes. Plasma was directly applied on the vessel system CAV for different exposure times to investigate irritative effects (hemorrhage, vascular lysis, thrombosis, lethality) up to 24 h. P. aeruginosa (PA) was further co-cultivated on the CAV, followed by CAP treatment to determine survival rate over 68 h. PA was cultivated on MH2-agar plates and treated with CAP to evaluate antimicrobial activity in vitro by formation of zones of inhibition (agar diffusion test). Results Treatment of hen's egg with the plasma jet caused hemorrhagic events and vascular lysis followed by lethal events, whereas the DBD plasma demonstrated high compatibility with only sporadic hemorrhagic reactions. Hence, further antimicrobial studies were performed with the DBD plasma. Without treatment, co-cultivation of PA on the CAV caused strong hemorrhagic reactions and embryonic lethality within 24 h. Treatment of PA with the DBD plasma increased the survival rate of the chick embryo depending on exposure times. The in vitro agar test confirmed the good antimicrobial efficiency. Conclusions The modified hen's egg test allows the determination of antimicrobial activity and biocompatibility of novel CAP sources for biomedical applications in a complex biological system. An efficient antimicrobial activity accompanied with a good biocompatibility was observed for the DBD plasma source.
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