Absolute basophil count is associated with time to recurrence in patients with high-grade T1 bladder cancer receiving bacillus Calmette-Guérin after transurethral resection of the bladder tumor.

BACKGROUND: Basophils, eosinophils and monocytes may be involved in BCG-induced immune responses and be associated with outcomes of bladder cancer patients receiving intravesical BCG. Our objective was to explore the association of baseline counts of basophils, eosinophils and monocytes with outcomes of patients with high-grade T1 bladder cancer receiving a standard course of intravesical BCG. METHODS: We retrospectively reviewed medical records of patients with primary T1 HG/G3 bladder cancer. After re-TURBT, patients were treated with a 6-week course of intravesical BCG induction followed by intravesical BCG every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months from initiation of therapy The analysis of potential risk factors for recurrence, muscle invasion and cancer-specific and overall survival was performed using univariable Cox regression models. Those factors that presented, at univariate analysis, an association with the event at a liberal p < 0.1, have been selected for the development of a multivariable model. RESULTS: A total of 1045 patients with primary T1 HG/G3 were included. A total of 678 (64.9%) recurrences, 303 (29.0%) progressions and 150 (14.3%) deaths were observed during follow-up. Multivariate analysis showed that logarithmic transformation of basophils count was associated with a 30% increment in the hazard of recurrence per unit increase of logarithmic basophils count (HR 1.30; 95% confidence interval 1.09-1.54; p = 0.0026). Basophil count modeled by quartiles was also significantly associated with time to recurrence [second vs. lower quartile HR 1.42 (1.12-1.79); p = 0.003, third vs. lower quartile HR 1.26 (1.01-1.57); p = 0.041; upper vs. lower quartile HR 1.36 (1.1-1.68); p = 0.005]. The limitations of a retrospective study are applicable. CONCLUSION: Baseline basophil count may predict recurrence in BCG-treated HG/G3 T1 bladder cancer patients. External validation is warranted.

Predictors of oncological outcomes in T1G3 patients treated with BCG who undergo radical cystectomy.

PURPOSE: To evaluate the oncological impact of postponing radical cystectomy (RC) to allow further conservative therapies prior to progression in a large multicentre retrospective cohort of T1-HG/G3 patients initially treated with BCG. METHODS: According to the time of RC, the population was divided into 3 groups: patients who did not progress to muscle-invasive disease, patients who progressed before radical cystectomy and patients who experienced progression at the time of radical cystectomy. Clinical and pathological outcomes were compared across the three groups. RESULTS: Of 2451 patients, 509 (20.8%) underwent RC. Patients with tumors > 3 cm or with CIS had earlier cystectomies (HR = 1.79, p = 0.001 and HR = 1.53, p = 0.02, respectively). Patients with tumors > 3 cm, multiple tumors or CIS had earlier T3/T4 or N + cystectomies. In patients who progressed, the timing of cystectomy did not affect the risk of T3/T4 or N + disease at RC. Patients with T3/T4 or N + disease at RC had a shorter disease-specific survival (HR = 4.38, p < 0.001), as did patients with CIS at cystectomy (HR = 2.39, p < 0.001). Patients who progressed prior to cystectomy had a shorter disease-specific survival than patients for whom progression was only detected at cystectomy (HR = 0.58, p = 0.024) CONCLUSIONS: Patients treated with RC before experiencing progression to muscle-invasive disease harbor better oncological and survival outcomes compared to those who progressed before RC and to those upstaged at surgery. Tumor size and concomitant CIS at diagnosis are the main predictors of surgical treatment while tumor size, CIS and tumor multiplicity are associated with extravesical disease at surgery.

Recurrence, progression and cancer-specific mortality according to stage at re-TUR in T1G3 bladder cancer patients treated with BCG: not as bad as previously thought.

PURPOSE: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG. METHODS: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model. RESULTS: During a median follow-up of 5.2 years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P < 0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P < 0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen. CONCLUSIONS: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease.

The association and reliability of the frontal plane projection angle during the lateral step down test on knee function in patients with patellofemoral pain.

BACKGROUND: The lateral step-down test is used by physical therapists (PT) to identify movement faults in patients with patellofemoral pain (PFP). The FPPA is a measure of knee valgus and PTs have access to open source video analysis software and high quality smart phones and video cameras to implement 2D video analysis into practice. The purpose of our study was to determine the reliability of PTs measuring the frontal plane projection angle (FPPA) during the lateral step-down test, and to determine if the FPPA was associated with pain, self-reported knee function and fear of movement. METHODS: Twenty-two subjects (mean age[SD] = 27.8 [6.6] years, females n = 14, males n = 8) with PFP were analyzed by six PTs using 2D video analysis software. The FPPA was measured during the lateral step down test. Numeric Pain Rating Scale (NPRS), Anterior Knee Pain Scale (AKPS) and the Tampa Scale of Kinesiophobia (TSK) were collected. Intraclass correlation (ICC) was used to assess for PT measurement reliability. Correlations between outcomes were calculated using Spearman correlation coefficient and standard error of measurement (SEM) and minimal detectable change (MDC) were reported. RESULTS: Reliability amongst PTs measuring the FPPA was good (ICC [95 %CI] = 0.85 [0.72-0.93]; SEM = 3.33°, MDC = 9.20°). There were no significant correlations (p > 0.05) between FPPA and NPRS(ρ = -0.046), AKPS(ρ = 0.066), or TSK(ρ = -0.204). CONCLUSIONS: Although reliability measuring FPPA was good, the large SEM and MDC associated with this measurement may limit its clinical utility in those with PFP.

Biomechanical measures of clinician-defined unsteadiness during a forward stepdown task in individuals post-arthroscopy for femoroacetabular impingement syndrome.

BACKGROUND: Patients with femoroacetabular impingement syndrome can present with aberrant movement patterns including unsteady balance. Balance training is included in rehabilitation after hip arthroscopy and may improve quality of movement; however, specific biomechanical measures associated with clinician-defined balance impairments are unknown. We aimed to understand these associations as they may inform targeted rehabilitative interventions. METHODS: The forward stepdown is a clinical test used to evaluate movement quality, including balance. 23 individuals at least one-year post-arthroscopy for femoroacetabular impingement syndrome and 15 healthy comparisons performed the forward stepdown, recorded by 3-dimensional motion capture and 2-dimensional video. Three physical therapists graded the 2-dimensional video for steadiness. Two-way analyses of variance were used to evaluate the interaction of group (post-arthroscopy/healthy comparison) by steadiness (steady/unsteady), for center of pressure medial-lateral excursion, center of pressure path length, and lateral trunk, pelvis, and lower extremity joint excursions. FINDINGS: Six (26.1%) participants post-arthroscopy and five (33.3%) healthy comparisons were categorized as unsteady. The odds of being categorized as unsteady were not greater for participants post-arthroscopy (P = 0.72). There were no significant interactions; however, participants with clinician-defined unsteady balance, regardless of group, had significantly greater frontal plane trunk excursion, greater hip excursion, and greater center of pressure path length than those with steady balance (P ≤ 0.006). INTERPRETATION: The odds of being categorized as unsteady were not greater for individuals post-arthroscopy for femoroacetabular impingement syndrome. Clinician-defined unsteadiness was associated with greater frontal plane trunk and hip motion which may be rehabilitation targets to improve balance during a dynamic single-leg task.

Risk factors for residual disease at re-TUR in a large cohort of T1G3 patients.

INTRODUCTION AND OBJECTIVES: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR. MATERIAL AND METHODS: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. RESULTS: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors > 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001. CONCLUSIONS: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.

Regulation of PDE5 expression in normal prostate, benign prostatic hyperplasia, and adenocarcinoma.

BACKGROUND: Type 5 phosphodiesterase (PDE5) expression in the normal and pathological prostate is controversial. OBJECTIVES: This study aimed at identifying the cell type/s, if any, expressing PDE5 in human healthy or pathological prostate sections in order to further validate the rationale of PDE5 inhibitor (PDE5i) treatment of benign prostatic hyperplasia (BPH) and their safety in the treatment of erectile dysfunction following prostate cancer (PCa) surgery. MATERIALS AND METHODS: By immunohistochemical analysis, we studied PDE5 expression in tissue microarrays containing sections obtained from healthy, BPH, and PCa samples. RESULTS: Our results showed that PDE5 is barely expressed in the epithelial or stromal compartment of normal human prostates, but it is highly expressed in the stromal compartment of BPH sections. We also found that a low but significant number of PCa samples (22%) expressed PDE5 in the epithelial cancer cells but not in stromal cells and that such expression was not correlated with the tumor aggressiveness, according to their Gleason score. DISCUSSION AND CONCLUSION: PDE5 overexpression in the stromal compartment of BPH samples supports the rationale of PDE5 as a target in lower urinary tract symptoms of BPH. PDE5 expression in a significant percentage of PCa samples but the lack of correlation with the Gleason score suggests that this enzyme is not correlated with tumor aggressiveness; however, a role of PDE5 in the minimal residual disease of PCa cannot be excluded.

Test-retest reliability and minimum detectable change for various frontal plane projection angles during dynamic tasks.

OBJECTIVE: Establish between-day test-retest reliability metrics for 2-dimensional frontal plane projection angles (FPPAs) during the lateral step-down (LSD), single-limb squat (SLS), single-limb landing (SLL), and drop vertical jump (DVJ). DESIGN: Test-retest reliability study. SETTING: University laboratory. PARTICIPANTS: 20 healthy adults (12 female, age = 23.60 ±â€¯1.93 years old, body mass index = 24.26 ±â€¯2.54 kg/m2) were tested on 2 separate occasions 7-14 days apart. MAIN OUTCOME MEASURES: Intraclass correlation coefficients (ICC), standard errors of the measurement (SEM), and minimal detectable change (MDC) values across the LSD, SLS, SLL, and DVJ for the following body region variables: trunk, trunk on pelvis, pelvis, hip, thigh to vertical, knee, and shank to vertical. RESULTS: There was moderate-to-substantial between-day test-retest reliability for nearly all body regions across all tasks (ICC = 0.65-0.96). SEM values varied across body regions and tasks (0.9-3.5°). MDCs were variable (2.3-9.8°). Of the body regions, MDCs were largest for the knee and hip. By task, MDCs were lowest for the LSD. CONCLUSIONS: This study identified between-day test-retest reliability metrics for 2-dimensional FPPAs across a variety of body regions during commonly assessed clinical tasks. These data allow clinicians and researchers to more confidently assess true change between assessments or over time.

Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics.

BACKGROUND: Tumor recurrence is the most expected clinical event after the resection of non-muscle invasive bladder cancer, depending on histological findings of the initial lesion. In patients with low and intermediate risk of disease, the intravesical instillation of chemotherapy agents is recommended as a standard treatment to reduce recurrences. METHODS: A comprehensive review covering various aspects of different treatments with intravesical drugs is presented. RESULTS: Drugs may be instilled into the bladder starting with a single, 'early' postoperative administration or, after tumor resection with adjuvant intent or, before tumor resection under a neo-adjuvant regimen. Both latter protocols would consist of weekly treatments followed by monthly maintenance treatments. Different methods of administering drugs intravesically have been proposed to enhance the depth of drug penetration and its absorption into the bladder wall thus increasing the rate of drug-DNA reaction. These device-assisted therapies therefore have set a goal to potentiate the drug's effect and efficaciousness. The Radiofrequency-Induced Thermochemotherapeutic Effect (RITE) and the Electromotive-Drug Administration (EMDA) are the two most relevant modalities used to increase the activity of intravesical chemotherapy. Despite the widely adopted international guidelines' recommendations, and recent clinical trials of device-assisted chemotherapy instillations showing markedly enhanced recurrence-free survival compared even to the standard of care, clinicians and pharmacologists are not familiar with the in-depth physical aspects, pharmacokinetics and systemic absorption of chemotherapeutic drugs following their intravesical administration. CONCLUSION: Knowledge of drug diffusion mechanisms into the tissue and cellular cytoplasm following bladder instillation is a key to understand the safety profile and clinical activity of chemotherapy.

Electromotive delivery of mitomycin C into human bladder wall.

The aim of this investigation was to establish an appropriate tissue pharmacokinetic model to compare concentrations of mitomycin C (MMC) in the human bladder wall after either passive delivery or electromotive administration (EMDA) and to evaluate the effects of EMDA on tissue morphology and MMC structure. Tissue sections of human bladder were inserted into two chamber cells with urothelium exposed to donor compartments containing MMC (10 mg in 100 ml of 0.24% NaCl solution) and an anode and with serosa exposed to receptor compartments containing 100 ml of 0.9% NaCl solution and a cathode. Fourteen paired experiments ("current 5 mA/no current") were conducted over 15 min; MMC tissue content was assessed by high-pressure liquid chromatography. Tissue viability and morphology and MMC stability were assessed by trypan blue exclusion test, tissue pH, histological analysis, and mass spectrometry analysis. MMC concentrations were increased, and variability in drug delivery rate was reduced in all tissue in samples exposed to electric current. Tissues were viable and undamaged histologically, and no MMC structural modification was observed. In conclusion, EMDA enhances administration of MMC into viable bladder wall tissue and reduces the variability in drug delivery rates.

Electromotive versus passive diffusion of mitomycin C into human bladder wall: concentration-depth profiles studies.

The objectives of these investigations were: (a) to make a preliminary study to assess concentration-depth profiles of mitomycin C (MMC) in the bladder wall at specified time intervals after passive diffusion (PD); and (b) to conduct a major study to compare concentration-depth profiles after PD and electromotive drug administration (EMDA) of MMC. Full thickness sections of viable human bladder wall were placed in two-chamber cells with urothelium exposed to donor compartments containing 40 mg of MMC in 100 ml of 0.96% NaCl solutions and with serosa-facing receptor compartments containing 0.9% NaCl solutions. In the preliminary study during each of nine experimental sessions, five sections of bladder wall were individually exposed to MMC for either 5, 15, 30, 45, or 60 min. In the major study, an anode and a cathode were sited in the donor and receptor compartments, and 14 paired experiments--current (20 mA)/no current--were conducted over a 30-min period. Bladder wall sections were cut serially into 40-microm slices parallel to the urothelium and analyzed by high-performance liquid chromatography for MMC concentration (microg/g wet tissue weight). Tissue viability and morphology and MMC stability were assessed by trypan-blue exclusion test, histological examination, and mass spectrometry analysis. In the preliminary study (PD only), mean MMC concentrations (microg) at 5, 15, 30, 45, and 60 min were: (a) for urothelium, 15.3, 60.0, 58.2, 60.1, and 57.8, respectively; (b) for lamina propria, 2.2, 18.9, 19.3, 16.1, and 17.3, respectively; and (c) for muscularis, 0.4, 2.0, 1.8, 1.3, and 2.4, respectively. In the comparative study, MMC concentrations and coefficients of variation (CV) were as follows: (a) for urothelium after PD, 46.6 with CV = 69%, and after EMDA, 170.0 with CV = 43% (P < 0.0001); (b) for lamina propria after PD, 16.1, with CV = 60%, and after EMDA, 65.6 with CV = 29% (P < 0.0001); and (c) for muscularis after PD, 1.9 with CV = 82%, and after EMDA, 15.9 with CV = 82% (P < 0.0005). All of the bladder sections remained viable, and the chemical structure of MMC was unchanged. It was concluded that EMDA significantly enhances MMC transport into all of the layers of the bladder wall, and sections of viable human bladder are a reliable tool for assessing different modes of drug delivery.

New therapeutic options for refractory neurogenic detrusor overactivity.

AIM: Current pharmacologic treatment of detrusor overactivity relies on anticholinergic drugs. However, they often have untolerable side effects so that they are administered in doses insufficient to restore urinary continence. Recently, intravesical instillations and injections into the detrusor muscle of new pharmacological agents have been developed. The present study report our own experience in the treatment of detrusor overactivity with intravesical administrations of vanilloid agents and with botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients. In particular, we compared the clinical and urodynamic effects of the 2 drugs in an attempt to find a new and valid therapeutic option in those cases unresponsive to conventional treatment. METHODS: Seventy-five patients with spinal cord injury and refractory detrusor overactivity were included in the study: 35 patients received repeated intravesical instillations of resiniferatoxin (RTX) dissolved in normal saline; 40 patients received repeated injections of 300 units botulinum A-toxin diluted in 30 ml normal saline. Clinical assessment and urodynamics were performed at baseline and 6, 12 and 24 months after treatment. RESULTS: With both treatments there was a significant reduction in mean catheterization and episodes of incontinence and a significant increase in mean first involuntary detrusor contraction and in mean maximum bladder capacity at 6, 12 and 24 months after therapy. We did not detect any local side effects with either treatment. Botulinum-A toxin significantly reduced also the maximum pressure of uninhibited detrusor contractions more than RTX at all follow-up time points. CONCLUSION: In patients with spinal cord injury and refractory detrusor overactivity intravesical RTX and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with reduction of detrusor overactivity and restoration of urinary continence in most patients. Botulinum-A toxin injection provided better clinical and urodynamic benefits than intravesical RTX.

[Echography in prostatitis]. / Ecografia nelle flogosi prostatiche.

In many infertile patients abnormalities in sperm are due to prostatic inflammatory disease. In the male reproductive system temporary episodes of inflammation, caused by newly discovered micro-organisms such as Chlamydia Trachomatis and Ureaplasma Urealyticum, may occur frequently and cause sub-clinical inflammation. This rapidly became chronic and induce the development of anti-spermatozoon antibodies. This latent clinical pattern and lack of symptoms often means diagnosis is late and medical treatment inadequate. In recent years attention has been focused on transrectal ultrasonography as a possible gold standard for diagnosing prostatic inflammatory disease. Widespread use of technologically advanced instruments has significantly improved the quality and definition of prostatic images. This paper discusses the current role of transrectal ultrasonography in the diagnosis of prostatic inflammatory disease. Abnormalities in the ultrasound pattern, caused by infection, are analyzed in detail and discussed critically in order to assess their role as markers of prostatic inflammation.

[Color Doppler echography in the diagnosis of nonspecific granulomatous prostatis: personal experience]. / L'ecocolor Doppler nella diagnosi di prostatite granulomatosa aspecifica: esperienza personale.

Non-specific granulomatous prostatitis (NSGP) is a rare but important pathology of the prostate because it often is confused with prostatic cancer. In fact, NSGP, presents at digital rectal examination as an area of increased consistency and painful, and at endorectal ultrasonography as an hypoechoic area with inhomogeneous echo structure. The frequent elevation of Prostatic-Specific Antigen (PSA) serum level vanish, moreover, its role of a differential factor. Since 1994 we used Echo-color doppler (ECD) in the evaluation of prostate cancer with satisfying results. The aim of our work is to value the route of ECD in the diagnosis of NSGP, and in the differential diagnosis with prostate cancer, actually only bioptic . Since January 1994 we observed 9 cases of NSGP; 7 patients with prostatic symptomatology and 2 with PSA serum level between 4 and 10 ng/ml. In all patients we performed endorectal US who showed, in 7 cases, nodular hypoechoic areas in the peripheral or central zone of the prostate, and in 2 cases the presence of evident BPH. In 5/7 cases with hypoechoic areas, ECD-US showed an increase of color intensity intra-perinodular. In 2 patients with BPH no marked color enhancement was observed. The diagnosis of NSGP has been done after needle biopsy in the 7 patients with suspect nodular areas, and in the 2 patients with BPH, after histological examination secondary to open prostatectomy. Our experience shows that ECD-US scanning picture in NSGP is superimposable with the prostatic cancer one. In fact the anatomical presupposition on the grounds of the "positivity" in ECD-US, focal hypervascularization, is present in ECD scanning pictures of both pathologies. In conclusion, ECD doesn't give an advantage in the differential diagnosis between NSGP and prostate cancer that actually remains only bioptic .

[Intravesical Electromotive Drug Administration®(EMDA)with Mitomycin-C for non-muscle invasive bladder cancer].

Electromotive Drug Administration® (EMDA) offers a means of controlling and enhancing the tissue transport of certain drugs, when applied to a surface epithelium, where they have a local therapeutic effect, in order to increase their efficacy. One application option is the treatment of non-muscle invasive bladder cancer with intravesical mitomycin-C (MMC). Laboratory studies demonstrated that EMDA/MMC can reduce the variability and enhance the drug administration rate into all layers of the bladder wall, and that the applied electric current causes no histological damage to tissue and no chemical modification of MMC. A prospective randomized study, performed in patients with in situ carcinoma, validated the prediction that electromotive enhancement of MMC delivery would provide results superior to those achieved using passive MMC transport. A further randomized study in patients with pT1 bladder cancer demonstrated that a regimen combining intravesical BCG and EMDA/MMC increased the disease-free interval and reduced the recurrence rate, as well as the disease progression and mortality rate if compared with BCG alone. The possibility that BCG may enhance the efficacy of MMC against high-grade pT1 transitional cell carcinoma and in situ carcinoma represents an important new therapeutic perspective in the high-risk non-muscle invasive bladder cancer.

Psychosocial issues of ART in aging male.

The role of androgens in human sexuality as regards the mechanism of erection and the pathogenesis of impotence is under debate. In addition, it is difficult to define the psychosocial impact of both hypogonadism and androgen replacement. However, sexual hormones largely influence mood, well-being, and quality of life. For this reason, despite the methodological difficulties of assessment, testosterone replacement has a deep impact on the social, psychological and sexual life of the treated patient. Considering the obvious characteristic of testosterone as an hormone, it appears evident that the endocrinologist is the unique experienced specialist able to diagnose and treat the hypogonadal men, monitoring potential side effects and following the psychosocial issues of androgen therapy.

Successful management of retroperitoneal malignant fibrous histiocytoma involving both kidneys.

We report a rare case of a retroperitoneal inflammatory variant of malignant fibrous histiocytoma (MFH) involving both kidneys. The best treatment for MFHs is surgery with radical excision of the tumor. In this case the need to save at least one kidney meant tumorectomy was incomplete. The patient underwent adjuvant chemotherapy and 4 years later survives in a fairly good condition.

Intralesional alpha interferon therapy in papillary superficial transitional cell carcinoma of the bladder. A pilot study.

The tolerability, toxicity and therapeutic efficacy of recombinant interferon alpha-2a (rIFN alpha-2a), administered by intralesional injection, were evaluated in 15 patients with papillary superficial transitional cell carcinoma of the bladder, rIFN alpha-2a was delivered endoscopically in a single weekly dose of 3 x 10(6) IU for 4 weeks (total 12 x 10(6) IU). Transurethral resection of residual tumours was then performed. The response to treatment was assessed according to ultrasonographic, endoscopic and pathological findings. One patient achieved complete remission, 6 partial remission, 6 minor remission and 2 stabilisation of disease. All patients completed the course of treatment. A mild, transient, flu-like syndrome was documented after every injection. Immunological findings suggest that the antitumour effects of rIFN alpha 2a are not mediated through the immune system.

Electromotive administration of oxybutynin into the human bladder wall.

PURPOSE: To compare concentrations of oxybutynin in the human bladder wall after either passive delivery (PD) or electromotive administration (EMDA). MATERIALS AND METHODS: Tissue sections of human bladder were inserted into a diffusion cell with urothelium exposed to the donor compartment containing oxybutynin (4.5 mg. in 100 ml. NaCl 0.45%) and an anode. Twelve paired experiments, "current 5 mA/no current", were conducted over 15 minutes. Oxybutynin tissue contents were measured and tissue viability, morphology and oxybutynin stability were assessed. RESULTS: Mean oxybutynin tissue concentrations were 3.84 micrograms./gm. in samples exposed to EMDA and 0.87 microgram./gm. in samples exposed to PD (p = 0.0006). The mean coefficients of variation were 57.85% in EMDA experiments and 89.78% in PD experiments. Tissues were viable and undamaged histologically and no oxybutynin structural modification was observed. CONCLUSIONS: EMDA enhances oxybutynin administration into viable bladder wall and reduces the variability in drug delivery rate.