Methodology of superficial bladder cancer trials: objective evaluation of treatment - the need for standardization.

The formulation of proper evaluation criteria after superficial bladder cancer therapy poses several methodological problems that are often peculiar to the disease. The Achilles' heel of many trials is possibly found in the criteria used in the evaluation of the trial's outcome. As a consequence, total agreement regarding the criteria for response and the evaluation of response is needed. The adoption of standard response criteria should be given high priority. Uniform criteria of response should be chosen because they meet standards of reliability and statistical validity. Thus, the criteria must be reproducible and correlate with some measures of patient benefit such as quantity and quality of survival. A proposal for standardization in superficial bladder cancer clinical trials is presented based upon the current knowledge of methodology used for conducting clinical trials and upon the experience coming from clinical research groups.

Bladder tumor markers: a review of the literature.

Bladder cancer is among the top eight most frequent cancers. Its natural history is related to a combination of factors that impact on its aggressiveness. Cystoscopy and urine cytology are the currently used techniques for the diagnosis and surveillance of non-invasive bladder tumors. The sensitivity of urine cytology for diagnosis is not high, particularly in low-grade tumors. The combination of voided urine cytology and new diagnostic urine tests would be ideal for the diagnosis and follow-up of bladder cancer. However, in order to have some clinical utility, new diagnostic and/or prognostic markers should achieve better predictive capacity that the currently used diagnostic tools. None of the markers evaluated over the last years showed remarkable sensitivity or specificity for the identification of any of the diverse types of bladder cancer in clinical practice. The limitations of the known prognostic markers have led to the research of new molecular markers for early detection of bladder cancer. This research focused in particular on the discovery of biomarkers capable of reducing the need for periodic cystoscopies or, ideally, offering a non-invasive examination instead. In this review, we will examine various new markers of bladder cancer and their value in the diagnosis and follow-up of non-muscleinvasive bladder cancer. When compared with urine cytology, which showed the highest specificity, most of these markers demonstrated an increased sensitivity.

In vitro effect of amikacin on rat and human detrusor muscle contraction.

INTRODUCTION: Normal and abnormal bladder contractions are principally mediated by acetylcholine released from postganglionic parasympathetic nerves. Since amikacin was reported to affect neurotransmission by a prejunctional mechanism, we investigated the effect of amikacin on isolated detrusor smooth muscle contraction to further evaluate its potential relaxant properties. MATERIALS AND METHODS: Detrusor smooth muscle obtained from 15 rats and 8 patients undergoing surgery were studied through measurement of isometric muscular contraction induced with electrical field stimulation (EFS) (10-60 Hz), carbachol (10(-7) to 10(-3)M) and nicotine (10(-7) to 10(-3)M) in the presence or absence of 1 mM amikacin in a low-Ca medium. RESULTS: Amikacin (1 mM) significantly reduced EFS-induced contraction of isolated rat and human detrusor muscle by 33 +/- 6.57% (p < 0.005) and 40 +/- 1.14% (p < 0.001), respectively. Contraction was restored after addition of calcium chloride (1 mM). The effect of amikacin was comparable to that of magnesium ions. Rat and human detrusor contractile response to nicotine was inhibited by 70 +/- 8.27% (p < 0.001) and 64 +/- 14.09% (p < 0.01) after the addition of amikacin (1 mM), while no significant effect was observed on carbachol-induced stimulation. CONCLUSION: Amikacin significantly inhibited detrusor contraction evoked by prejunctional stimulation in vitro, suggesting a depressant effect on autonomic neurotransmission in urinary bladder.

[Prostatitis syndromes and sporting activities]. / Sindromi prostatiche e sport.

INTRODUCTION: Prostatitis-like syndromes are high prevalent health problems and frequently considered by patients and physicians as strictly correlated to sports causing perineal compression. These syndromes and their relationships with sporting activities have been discussed in this report. METHODS: We reviewed peer-reviewed scientific articles published by May 2009 and searched according to the following term selection: prostatitis, pudendal nerve, sport, cycling. RESULTS: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a major healthcare burden heavily affecting patients' Quality of Life. No clear evidence of any direct etiologic relationship has been found in literature between prostatitis, either bacterial or non-bacterial, and sports activities. On the other hand, some types of sport causing perineal compression, such as cycling, can exacerbate symptoms of acute and chronic prostatitis; a temporary sport discontinuation is justified in these patients. CP/CPPS may be often caused by pudendal nerve entrapment (PNE). Prostatitis-like urogenital neuropathic pain together with voiding and sexual dysfunctions are the hallmark of PNE. A common feature is that flexion activities of the hip, such as climbing, squatting, cycling provoke or worsen urogenital pain or pelvic pain. Many of the patients with PNE are cyclists, played American football, lifted weights, or wrestled as teenagers and young adults. PNE represents the most common bicycling associated urogenital problems. CONCLUSIONS: Overall, studies show that no causal relationship has been demonstrated between prostatitis and sporting activities. Conversely, urologists should be aware that sports involving vigorous hip flexion activities or prolonged perineal compression are a potential and not an infrequent cause of uroandrological symptoms caused by pudendal nerve entrapment.

[Sports and genitourinary traumas]. / Sport e traumi genitourinari.

INTRODUCTION: Statistical data referring to sports-related traumas of the urinary tract are quite scarce; nevertheless, it is possible to draw general data on the relationship between sports and urological traumas. METHODS: Literature review of peer-reviewed articles published by May 2009. RESULTS: Urological traumas account for about 10% of all traumas, and about 13% of them is sports-related. Genitourinary traumas are among the most common cause of abdominal injuries in sports. Blunt injuries are more common than penetrating ones and renal injuries are by far the most common, followed by testicular injuries; ureters, bladder and penis injuries are much more infrequent. Considering chronic microtraumas, injuries of bulbar urethra are also common in sports that involve riding. Overall, the incidence of genitourinary trauma due to sports is low. Renal traumas in sports injuries usually consist of grade I-II lesions and usually do not require surgical treatment. Cycling is the sporting activity most commonly associated with genitourinary injuries, followed by winter sports, horse riding and contact/collision sports. Literature data suggest that significant injuries are rare also in athletes with only one testicle or kidney. General preventive measures against sport-related injuries, along with the use of protective cups for male external genitalia, are generally sufficient to reduce the incidence of urogenital trauma. CONCLUSIONS: Overall, studies show that urogenital injuries are uncommon in team and individual sports, and that most of them are low-grade injuries. Participation in sports that involve the potential for contact or collision needs to be carefully assessed in the athletes with only one testicle or kidney, even though urogenital injuries should not preclude sports participation to an appropriately informed and counseled patient. Further research is needed to acquire more knowledge on genitourinary injuries according to age, sports type and technical skill.

[Doping and urologic tumors]. / Doping e neoplasie urologiche.

Several substances such as growth hormone (GH), erythropoietin (Epo), and anabolic steroids (AS) are improperly utilized to increase the performance of athletes. Evaluating the potential cancer risk associated with doping agents is difficult since these drugs are often used at very high doses and in combination with other licit or illicit drugs. The GH, via its mediator, the insulin-like growth factor 1 (IGF-1), is involved in the development and progression of cancer. Animal studies suggested that high levels of GH/IGF-1 increase progression of androgen-independent prostate cancer. Clinical data regarding prostate cancer are mostly based on epidemiological studies or indirect data such as IGF-1 high levels in patients with prostate cancer. Even if experimental studies showed a correlation between Epo and cancer, no clinical data are currently available on cancer development related to Epo as a doping agent. Androgens are involved in prostate carcinogenesis modulating genes that regulate cell proliferation, apoptosis and angiogenesis. Most information on AS is anecdotal (case reports on prostate, kidney and testicular cancers). Prospective epidemiologic studies failed to support the hypothesis that circulating androgens are positively associated with prostate cancer risk. Currently, clinical and epidemiological studies supporting association between doping and urological neoplasias are not available. Nowadays, exposure to doping agents starts more prematurely with a consequent longer exposition period; drugs are often used at very high doses and in combination with other licit or illicit drugs. Due to all these elements it is impossible to predict all the side effects, including cancer; more detailed studies are therefore necessary.

[Methodology of clinical trials for non-muscle infiltrating bladder cancer. Objective evaluation: standardization requirements].

The formulation of proper evaluation criteria after superficial bladder cancer therapy poses several methodological problems that are often peculiar to the disease. The Achilles' heel of many trials is possibly found in the criteria used for the evaluation of the trial outcomes. As a consequence of that, total agreement regarding the criteria for response and the evaluation of response is needed. The adoption of standard response criteria should be given high priority. Uniform response criteria should be chosen because they meet standards of reliability and statistical validity. Thus, the criteria must be reproducible, and they should correlate with some measures of patient's benefit, such as quantity and quality of survival. A proposal of standardization in superficial bladder cancer clinical trials is presented based upon current knowledge on the methodology for conducting clinical trials and upon the experience coming from major clinical research groups.

[Botulinum toxin in the treatment of overactive bladder].

Clinical effectiveness of botulinum toxin (BTX) in the treatment of both neurogenic and idiopathic detrusor overactivity has been demonstrated in several studies. However, different protocols and techniques have been used by authors. METHODS. Literature review on intradetrusor injection of BTX for detrusor overactivity. RESULTS. The greatest clinical experience reports the use of 200 and 300 U Botox®. Available data suggest that clinical efficacy, duration, and the side effect profile is similar at these doses. Very few data, on the other hand, are available regarding the clinical outcomes using the Dysport® preparation; isolated reports support that efficacy is similar when using a dosing range of 500 to 1000 SU with increased risk of systemic side effects using 1000 SU. A variety of injection volumes was used, demonstrating similar efficacy and tolerability profile. Clinical effect duration extends six to ten months in the majority of studies. Data suggest that a repeated injection scheme proves successful in the vast majority of initial responders. CONCLUSIONS. Safety, effectiveness, specificity and reversibility make BTX a new attractive treatment modality for overactive bladder syndrome. However, more experience is needed to standardize the injection protocol with respect to therapeutic outcomes and adverse effects.

[Amikacin: a novel modulator of vesical and prostate efferences. An in vitro experimental study].

The autonomic efferent neurotransmission to the bladder and prostate smooth muscle is a potential target for drug therapy of specific low urinary tract disfunction (LUTD). Since amikacin and other amynoglicosides were reported to affect neurotransmission by a pre-junctional mechanism, we investigated the effect of amikacin on isolated rat and human detrusor smooth muscle contraction and on isolated rat and human prostate contraction, to further evaluate its potential relaxant properties. MATERIALS AND METHODS. Samples of detrusor smooth muscle and prostate tissue, obtained from 97 rats and 16 patients undergoing surgery, were studied through the measurement of isometric contraction induced by electrical field stimulation (EFS) and other pharmacological stimuli in the presence or absence of 1mM amikacin in a low-Ca medium. RESULTS. Amikacin 1 mM significantly reduced contraction of isolated rat and human detrusor muscle and prostate, achieved with pre-junctional stimulation, while no significant effect was observed on contraction induced by pharmacological post-junctional stimulators. EFS contraction inhibited by amikacin was restored after addition of calcium chloride. The amikacin effect was comparable to the effect of magnesium ions, which are known to exert a pre-junctional inhibition of neurotransmitter release. CONCLUSIONS. Amikacin significantly inhibited rat and human detrusor and prostate contraction evoked by pre-junctional stimulation in vitro, suggesting a depressant effect on autonomic efferent neurotransmission. Further pharmacokinetics studies and researches on related compounds may hold potential for future development in the treatment of specific low urinary tract disfunction (LUTD).

[Human biobank in uro-oncological research].

PURPOSE. Uro-oncological translational research requires clinical data and human biological tissues collected within a biological tissue bank (BTB). We are hereby outlining ethic-legal, methodological and technical issues of a BTB establishment process, focusing particularly on prostate cancer and Italian setting. MATERIALS AND METHODS. Review of literature data, and national and international regulations and guidelines; direct field experience of urological BTB; counseling of the different professionals involved. RESULTS. Within a BTB establishment process, it is of utmost importance to protect the donors' privacy and rights through the programmatic adoption of the following procedures: 1) informed consent; 2) confidentiality protection thanks to anonymity of biological specimens and use of an "honest broker" method; 3) identification of a single responsible researcher; 4) dedicated and protected location; 5) approval of the Ethical Committee. There are two main organizational models of BTB: "systematic", i.e. collecting specimens from all patients and through the same methodology; "project-driven", i.e. prospectively selecting patients for a specific study and using the specific methods required by researchers. In the preliminary step it is necessary to establish detailed protocols of sampling and crioconservation techniques, and methods of validation and quality control. For prostate tissue sampling, several techniques have been described such as specimens of alternate slices, macro dissection, Tru-Cut. CONCLUSIONS. Today BTBs are necessary in order to support molecular and translational research in uro-oncology, and to overcome the limits of the research based only on clinicalpathological data. Ethic-legal and methodological issues related to BTBs are still requiring specific legislation and standardization of techniques.