| 1. |
- Bleeker, M. C. G., et al.
(författare)
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Penile cancer: epidemiology, pathogenesis and prevention
- 2009
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 27:2, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- Penile cancer is a disease with a high morbidity and mortality. Its prevalence is relatively rare, but the highest in some developing countries. Insight into its precursor lesions, pathogenesis and risk factors offers options to prevent this potentially mutilating disease. This review presents an overview of the different histologically and clinically identified precursor lesions of penile cancer and discusses the molecular pathogenesis, including the role of HPV in penile cancer development. A systematic review of the literature evaluating penile carcinogenesis, risk factors and molecular mechanisms involved. Careful monitoring of men with lichen sclerosis, genital Bowen's disease, erythroplasia of Queyrat and bowenoid papulosis seems useful, thereby offering early recognition of penile cancer and, subsequently, conservative therapeutic options. Special attention is given to flat penile lesions, which contain high numbers of HPV. Their role in HPV transmission to sexual partners is highlighted, but their potential to transform as a precursor lesion into penile cancer has been unsatisfactorily explored. Further research should not only focus on HPV mediated pathogenic pathways but also on the non-HPV related molecular and genetic factors that play a role in penile cancer development. Options for prevention of penile cancer include (neonatal) circumcision, limitation of penile HPV infections (either by prophylactic vaccination or condom use), prevention of phimosis, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation and hygienic measures.
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| 2. |
- Hedlund, Petter
(författare)
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Nitric oxide/cGMP-mediated effects in the outflow region of the lower urinary tract-is there a basis for pharmacological targeting of cGMP?
- 2005
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Ingår i: World journal of urology. - : Springer Science Business Media. - 0724-4983 .- 1433-8726. ; 23:6, s. 362-367
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with alpha-adrenoceptor antagonists that reduce the tone of prostatic stromal and urethral smooth muscle has beneficial effects in patients with benign prostatic hyperplasia (BPH) and lower urinary tracts symptoms (LUTS) and has brought attention to regulatory mechanisms of smooth muscle contractility of the outflow region. The prostate, urethra and bladder neck are densely supplied by nitric oxide (NO)-synthase-containing nerves that cause relaxation upon activation. In various experimental models, altered function or activity of the NO/cGMP pathway of the bladder neck and urethra may be related to inappropriate or un-coordinated functions of the bladder outlet and detrusor, but causal connections between alterations in this signaling system, a dysfunctional bladder outlet, and the development of LUTS are not established for humans. The present review focuses on regulatory functions of smooth muscle contractility by the NO/cGMP-pathway in the bladder neck, urethra, and prostate. Disease-related alterations in the NO/cGMP-pathway, and putative options for pharmacological modification of this signaling pathway in the out-flow region are briefly discussed.
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| 3. |
- Holmer, Magnus, et al.
(författare)
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Extended lymph node dissection in patients with urothelial cell carcinoma of the bladder: can it make a difference?
- 2009
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 27, s. 521-526
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We compared extended and limited lymph node dissections performed during radical cystectomy with regard to impact on survival and time to recurrence in bladder cancer patients. METHODS: We analyzed 170 patients who underwent radical cystectomy for urothelial carcinoma between January 1997 and December 2005. From 1997 to 2000, 69 of the patients were subjected to limited lymph dissection that included perivesical nodes and nodes in the obturator fossa. In 2001-2005, the remaining 101 patients underwent extended lymph dissection that included perivesical nodes; nodes in the obturator fossa; the internal, external, and common iliac nodes; and the presacral nodes. RESULTS: Tumors penetrating the bladder wall (pT3 and pT4a) were more common in the extended than in the limited dissection group (48 and 33%, respectively). The median numbers of lymph nodes removed in the two groups were 37 and 8, respectively. Lymph node metastases were detected in 38% of the extended dissection patients but only in 17% of the limited dissection patients. There was no significant difference in survival or time to recurrence between the two groups. Subgroup analyses showed a significantly longer time to recurrence (HR 0.45, 95% CI 0.22-0.93; P = 0.032) in patients with non-organ-confined disease who underwent extended lymph node dissection. In a multivariate analysis adjusting for tumor stage, lymph node status, age, sex, and adjuvant chemotherapy, there was a significantly improved survival (HR 0.47, 95% CI 0.25-0.88; P = 0.018) and time to recurrence (HR 0.42, 95% CI 0.23-0.79; P = 0.007) in the patients with extended lymph node dissections. CONCLUSIONS: Extended lymph node dissection did not improve disease-specific survival, but was in multivariate analysis related to significantly improved disease-specific survival and prolonged time to recurrence in radical cystectomy patients. These results should be interpreted cautiously, since they might have been affected by stage migration and the shorter follow-up in the extended dissection group.
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| 4. |
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| 5. |
- Steuber, Thomas, et al.
(författare)
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Circulating biomarkers for prostate cancer
- 2007
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 25:2, s. 111-119
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Tidskriftsartikel (refereegranskat)abstract
- Due to its significant applicability for early detection, risk prediction and follow-up evaluation, prostate specific antigen (PSA) has revolutionized our ability to treat prostate cancer patients. With the prevalent use of PSA for early detection during the last two decades, disease characteristics have been altered towards early detected, localized tumors with a high chance of cure following local therapy. This advantage faces the risk of overdetection and overtreatment. In addition, PSA lacks both, sensitivity and specificity to accurately detect patients at risk of prostate cancer. Therefore, novel biomarkers are urgently needed to improve identification of men at risk of having the disease and to predict the natural behaviour of the tumor. Recent advances in the evaluation of high-throughput technologies have led to the discovery of novel candidate markers for prostate cancer. This article will briefly discuss current PSA-based strategies and review several novel biomarkers for prostate cancer, detectable in blood.
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| 6. |
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| 7. |
- Uckert, S, et al.
(författare)
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Distribution and functional significance of phosphodiesterase isoenzymes in the human lower urinary tract
- 2005
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Ingår i: World journal of urology. - : Springer Science Business Media. - 0724-4983 .- 1433-8726. ; 23:6, s. 368-373
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Tidskriftsartikel (refereegranskat)abstract
- To date, it is widely accepted that several disorders of the male and female urogenital tract, such as erectile dysfunction, bladder overactivity, urinary stone disease and the benign prostatic syndrome, can be therapeutically approached by influencing the function of the smooth musculature of the respective organs. In order to achieve a pronounced drug effect without significant adverse events, especially on the cardiovascular system, a certain degree of tissue selectivity is mandatory. Selective intervention in intracellular pathways regulating smooth muscle tone has become a promising strategy to modulate tissue function. Since the concept of taking a pill as a cure for an illness or the relief of symptoms has become widely accepted by the consumers, the pharmacological treatment of urological diseases has focused on selective, orally available drugs, acting via influencing intracellular regulatory mechanisms, thus combining a high response rate and the advantage of an on-demand intake. PDEs play a central role in controlling the levels of cyclic nucleotides (i.e. cAMP and/or cGMP), which are important second messengers in many transmitter pathways involved in the regulation of biological processes of urogenital tissues. Specifically, the use of isoenzyme selective phosphodiesterase (PDE) inhibitors offers great hope in the medical treatment of various genitourinary diseases. These agents are regarded efficacious, having a fast onset of drug action in the target tissue and an improved effect-to-side-effect ratio. The growing experience with the use of this class of compounds in urology is mainly based on basic research efforts and this field will remain the most exciting and innovative subject in genitourinary physiology and pharmacology for the next few years. These tremendous research efforts may lead to a vast pharmacological armamentarium of possible new treatment options. The purpose of this review is to summarize the current knowledge on the distribution and potential functional significance of PDE isoenzymes in the human lower urinary tract.
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| 8. |
- Waldkirch, E, et al.
(författare)
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Cyclic AMP-specific and cyclic GMP-specific phosphodiesterase isoenzymes in human cavernous arteries - immunohistochemical distribution and functional significance
- 2005
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 23:6, s. 405-410
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: It has been well established that male erectile dysfunction is frequently associated with vascular diseases. The normal function of cavernous arteries is considered a prerequisite to maintain sufficient blood flow to the trabecular spaces in order to enable penile erection. Contractility of cavernous arteries is regulated by the peripheral autonomic nervous system and endogenous factors released from the endothelial cell layer. A significant increase of blood flow in the central cavernous arteries is the initial event leading to penile tumescence and rigidity. Besides the significance of the nitric oxide/cyclic guanosine monophosphate (cGMP)-mediated mechanisms, the cyclic AMP (cAMP) signalling pathway is also involved in the regulation of tone of the erectile tissue, and interactions between cGMP- and cAMP-mediated mechanisms have been demonstrated. The aim of the present study was to investigate by means of immunohistochemistry the presence of the phosphodiesterase (PDE) isoenzymes 3, 4 (cAMP-specific PDEs) and 5 (cGMP-specific PDE) in thin sections of human central cavernous arteries (HCA) and their functional significance in the mechanism of vessel tone regulation. Methods: Functional experiments were performed using circular segments of HCA and strip preparations of the human corpus cavernosum (HCC). Relaxant effects induced by the cumulative addition of the PDE inhibitors milrinone (PDE3 inhibitor), rolipram (PDE4 inhibitor) and sildenafil (PDE5 inhibitor; 0.01, 0.1, 1 and 10 M) were studied in preparations of HCA and HCC challenged by 1 M norepinephrine (NE). Moreover, immunohistochemistry was carried out in order to evaluate the expression of PDE3, PDE4 and PDE5 in thin sections of HCA. Results: Milrinone, rolipram and sildenafil dose-dependently reversed the NE-induced tension of the isolated vascular segments and HCC strips with sildenafil being the most effective drug. Neither rolipram nor milrinone reached an EC50 value. Abundant immunoreactivities specific for PDE3, PDE4 and PDE5 were observed in the entire smooth musculature of the wall of HCA and resistance arteries. In addition, immunoreactivity for PDE4 was also detected in the cytoplasm of endothelial cells lining the cavernous arteries. Conclusions: The cGMP-dependent relaxation of cavernous arteries is not only dependent on the normal function of the peripheral autonomic nervous system but also on the functional integrity of the vascular endothelium. The expression of the cGMP-specific PDE5 and the ability of the PDE5 inhibitor sildenafil to reverse the adrenergic tension of isolated segments of HCA underline the important role of the NO/cGMP pathway in the control of smooth muscle tone of human trabecular smooth musculature and penile cavernous arteries. Our results also suggest a significance of the cAMP-dependent signaling mechanisms in the regulation of tension of central HCAs. The present findings are also in support of the hypothesis of interactions between the cGMP- and cAMP-mediated signaling pathways in HCAs. Further investigations are indicated in order to outline potential differences between central HCAs and helicine resistance arteries. This may help to understand better the relations between structural and functional changes in the penile erectile tissue in patients with cardiovascular diseases and endothelial dysfunction.
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| 9. |
- Murta-Nascimento, C., et al.
(författare)
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Epidemiology of urinary bladder cancer: from tumor development to patient's death
- 2007
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Ingår i: World J Urol. - 0724-4983. ; 25:3, s. 285-295
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Tidskriftsartikel (refereegranskat)abstract
- Urinary bladder cancer (UBC) ranks ninth in worldwide cancer incidence. It is more frequent in men than in women. We review the main established/proposed factors, both environmental and genetic, associated with bladder cancer etiology and prognosis. Data were extracted from previous reviews and original articles identified from PubMed searches, reference lists, and book chapters dealing with the reviewed topics. Evaluation and consensus of both the contribution of each factor in bladder cancer burden and the appropriateness of the available evidences was done during an ad hoc meeting held during the 18th Congress of the European Society for Urological Research. Cigarette smoking and specific occupational exposures are the main known causes of UBC. Phenacetin, chlornaphazine and cyclophosphamide also increase the risk of bladder cancer. Chronic infection by Schistosoma haematobium is a cause of squamous cell carcinoma of the bladder. NAT2 slow acetylator and GSTM1 null genotypes are associated with an increased risk of this cancer. Vegetables and fresh fruits protect against this tumor. Regarding prognosis, there is little knowledge on the predictive role of environmental exposures and genetic polymorphisms on tumor recurrence and progression and patient's death. Although active tobacco smoking is the most commonly studied factor, no definitive conclusion can be drawn from the literature. More research is needed regarding the effect of complex etiological factors in bladder carcinogenesis. Subgroup analysis according to stage, grade, and molecular features may help in identifying specific etiological and prognostic factors involved in different bladder cancer progression pathways.
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