Urothelial Carcinoma of the Urinary Bladder in Young Adults: Presentation, Clinical behavior and Outcome.

Introduction. There is not much evidence regarding clinical behavior of bladder cancer in younger patients. We evaluated clinical characteristics, tumor recurrence and progression in patients younger than 40 years old with urothelial bladder carcinoma. Methods. We retrospectively reviewed the medical records of 31 patients less than 40 years old who were firstly managed with bladder urothelial carcinoma in our department. Data were analysed with the Chi-square test. Results. Mean age was 31.7 years. Mean followup was 38.52 months (11-72 months). Nineteen (61%) patients were diagnosed with GII and 2 (6%) patients with GIII disease. Five (16%) patients presented with T1 disease. Three (9%) patients with invasive disease underwent cystectomy and adjuvant chemotherapy and one developed metastatic disease. Ten (32%) patients recurred during followup with a disease free recurrence rate of 65% the first 2 years after surgery. From those, 1 patient progressed to higher stage and three to higher grade disease. No patient died during followup. Conclusions. Bladder urothelial carcinoma in patients younger than 40 years is usually low stage and low grade. Management of these patients should be according to clinical characteristics and no different from older patients with the same disease.

Activation of membrane androgen receptors potentiates the antiproliferative effects of paclitaxel on human prostate cancer cells.

Genomic signaling mechanisms require a relatively long time to get into action and represent the main way through which steroid hormones affect target cells. In addition, steroids may rapidly activate cellular functions by non-genomic signaling mechanisms involving membrane sites. Understanding in depth the molecular mechanisms of the non-genomic action represents an important frontier for developing new and more selective pharmacologic tools for endocrine therapies. In the present study, we report that membrane-impermeable testosterone-bovine serum albumin (BSA) acts synergistically with paclitaxel in modifying actin and tubulin cytoskeleton dynamics in LNCaP (androgen sensitive) and DU-145 (androgen insensitive) human prostate cancer cell lines. In addition, coincubation of either cell line with testosterone-BSA and paclitaxel induced inhibition of cell proliferation and apoptosis. Finally, in vivo experiments in LNCaP and DU-145 tumor xenografts in nude mice showed that both agents decrease tumor mass, whereas testosterone-BSA enhances the effect of paclitaxel. Our findings suggest that chronic activation of membrane androgen receptors in vitro and in vivo facilitates and sustains for a longer time the antitumoral action of cytoskeletal acting agents.

Membrane testosterone binding sites in prostate carcinoma as a potential new marker and therapeutic target: study in paraffin tissue sections.

BACKGROUND: Steroid action is mediated, in addition to classical intracellular receptors, by recently identified membrane sites, that generate rapid non-genomic effects. We have recently identified a membrane androgen receptor site on prostate carcinoma cells, mediating testosterone rapid effects on the cytoskeleton and secretion within minutes. METHODS: The aim of this study was to investigate whether membrane androgen receptors are differentially expressed in prostate carcinomas, and their relationship to the tumor grade. We examined the expression of membrane androgen receptors in archival material of 109 prostate carcinomas and 103 benign prostate hyperplasias, using fluorescein-labeled BSA-coupled testosterone. RESULTS: We report that membrane androgen receptors are preferentially expressed in prostate carcinomas, and they correlate to their grade using the Gleason's microscopic grading score system. CONCLUSION: We conclude that membrane androgen receptors may represent an index of tumor aggressiveness and possibly specific targets for new therapeutic regimens.

Membrane androgen receptor activation induces apoptotic regression of human prostate cancer cells in vitro and in vivo.

Nongenomic androgen actions imply mechanisms different from the classical intracellular androgen receptor (iAR) activation. We have recently reported the identification of a membrane androgen receptor (mAR) on LNCaP human prostate cancer cells, mediating testosterone signal transduction within minutes. In the present study we provide evidence that activation of mAR by nonpermeable, BSA-coupled testosterone results in 1) inhibition of LNCaP cell growth (with a 50% inhibitory concentration of 5.08 nM, similar to the affinity of testosterone for membrane sites); 2) induction in LNCaP cells of both apoptosis and the proapoptotic Fas protein; and 3) a significant decrease in migration, adhesion, and invasion of iAR-negative DU145 human prostate cancer cells. These actions persisted in the presence of antiandrogen flutamide or after decreasing the content of iAR in LNCaP cells by iAR antisense oligonucleotides. Testosterone-BSA was also effective in inducing apoptosis of DU145 human prostate cancer cells, negative for iAR, but expressing mAR sites. In LNCaP cell-inoculated nude mice, treatment with testosterone-BSA (4.8 mg/kg body weight) for 1 month resulted in a 60% reduction of tumor size compared with that in control animals receiving only BSA, an effect that was not affected by the antiandrogen flutamide. Our findings suggest that activators of mAR may represent a new class of antitumoral agents of prostate cancer.

Spontaneous perirenal hemorrhage: a 10-year experience at our institution.

OBJECTIVE: To report our experience in patients with spontaneous perirenal hemorrhage (SPH) seen at our institution over a 10-year period. MATERIAL AND PATIENTS: Over the years from 1992 to 2002, 13 patients with SPH without a history of trauma, were treated at our hospital. There were 5 male and 8 female patients with a mean age of 55.7 years (range 36-79 years). The patients' records were reviewed retrospectively with respect to etiology, clinical presentation, radiologic findings and therapeutic management of SPH. RESULTS: All patients were presented with flank or abdominal pain. Radiological evaluation included ultrasonography (U/S) in 7 cases and computed tomography (CT) in 13 cases. An underlying renal mass was indentified employing U/S in 2 cases and using CT in 10 cases respectively. The etiology of SPH was determined in 12 cases. The most common causes were angiomyolipoma (5 patients) and renal cell carcinoma (4 patients). Out of the remaining 4 cases with SPH, one was associated with anticoagulant therapy; polyarteritis nodosa and Wegener angeitis were the underlying diseases in 2 cases respectively; finally, the etiology could not be determined in 1 case. All but two patients were managed surgically. Complete nephrectomy was performed in 6 cases, partial nephrectomy in 4 and simple evacuation of the haematoma was performed in 1 case. CONCLUSIONS: SPH presence should arouse suspicions concerning its etiology, since the most common cause is a renal tumor and approximately 50% of such tumors are malignant. CT scanning is a useful imaging modality for the initial evaluation of SPH, permitting identification of the underlying cause in most instances.

Membrane androgen binding sites are preferentially expressed in human prostate carcinoma cells.

BACKGROUND: Prostate cancer is one of the most frequent malignancies in males. Nevertheless, to this moment, there is no specific routine diagnostic marker to be used in clinical practice. Recently, the identification of a membrane testosterone binding site involved in the remodeling of actin cytoskeleton structures and PSA secretion, on LNCaP human prostate cancer cells has been reported. We have investigated whether this membrane testosterone binding component could be of value for the identification of prostate cancer. METHODS: Using a non-internalizable testosterone-BSA-FITC analog, proven to bind on membrane sites only in LNCaP cells, we have investigated the expression of membrane testosterone binding sites in a series of prostate carcinomas (n = 14), morphologically normal epithelia, taken from areas of the surgical specimens far from the location of the carcinomas (n = 8) and benign prostate hyperplasia epithelia (n = 10). Isolated epithelial cells were studied by flow cytometry, and touching preparations, after 10-min incubation. In addition, routine histological slides were assayed by confocal laser microscopy. RESULTS: We show that membrane testosterone binding sites are preferentially expressed in prostate carcinoma cells, while BPH and non-malignant epithelial cells show a low or absent binding. CONCLUSIONS: Our results indicate that membrane testosterone receptors might be of use for the rapid routine identification of prostate cancer, representing a new diagnostic marker of the disease.

Assessment of patient effective radiation dose and associated radiogenic risk from extracorporeal shock-wave lithotripsy.

The aim of the present study was to calculate patient effective dose and associated radiogenic risk from fluoroscopy guided extracorporeal shock-wave lithotripsy procedures. Fluoroscopy required during extracorporeal shock-wave lithotripsy was classified in two types identified by beam orientation: antero-posterior and 30 degrees anterior-oblique projected exposures. Duration of each exposure was monitored in 124 patients undergoing extracorporeal shock-wave lithotripsy treatment for ureteral stones. The dose from a kidney-ureter-bladder radiograph and the dose per min of fluoroscopy along antero-posterior and anterior-oblique projections were measured at 13 organs/tissues using an anthropomorphic phantom and thermoluminescence dosimetry. A radio-opaque object was placed in the phantom to simulate an ureteral stone at the proximal and distal ureter. The total effective dose in male and female patients with proximal ureteral stones was 1.71 mSv and 1.82 mSv, respectively. The corresponding values for male and female patients with distal ureteral stones was 0.76 mSv and 1.62 mSv, respectively. In the United States, the theoretical sex-averaged radiogenic excess of fatal cancers was estimated to be 140 per million and 85 per million of patients treated for proximal and distal ureteral stone, respectively. The average radiogenic risk for genetic defect associated to treatments of proximal and distal ureteral stones was found to be 2.5 and 24.4 per million of births, respectively. The radiation risk from a typical fluoroscopy guided extracorporeal shock-wave lithotripsy treatment of ureteral stones is low. Presented data may be used to determine patient effective dose from extracorporeal shock-wave lithotripsy procedures performed in any laboratory.