Upper pole tumors with direct extension into the adrenal gland predict significantly worse survival than similarly staged tumors with fat invasion and they have a prognosis similar to that of stage pT4 disease. While these data await external validation, consideration should be given to re-categorizing tumors with direct adrenal gland involvement as stage pT4 or in a subcategory such as pT4a.

We investigated whether the improvement of lower urinary tract symptoms (LUTS) and urinary adenosine triphosphate (ATP) level were related. Fifty-seven patients and 13 normal controls were enrolled in this study. All of the male patients had benign prostatic hyperplasia (BPH), and all of the female patients had overactive bladder (OAB). We administered an alpha-1 adrenergic receptor antagonist (tamsulosin hydrochloride) for BPH, while OAB patients received an anti-muscarinic agent (propiverine hydrochloride). Before and after treatment, we examined LUTS and urinary ATP/creatinine ratio. The urinary ATP/creatinine ratio was lower in males than females in both controls and patients. In the BPH patients, administration of the alpha-1 receptor antagonist decreased LUTS and urinary ATP/creatinine ratio, and improvement of LUTS was greater in patients with a high baseline urinary ATP level. In the OAB patients, administration of the anti-muscarinic agent decreased LUTS and urinary ATP/creatinine ratio, and improvement of LUTS was greater in patients with a high baseline urinary ATP level. Improvement of LUTS by treatment with the alpha-1 receptor antagonist or the anti-muscarinic agent was related to the decrease of urinary ATP/creatinine ratio in patients with BPH or OAB. Measurement of urinary ATP can be used as a marker of pathologic bladder function.Alpha-1 adrenergic receptor antagonists are the firstline medications for the treatment of benign prostatic hyperplasia (BPH), because these drugs relax the smooth muscle in the prostate and decrease resistance to urine flow in the prostatic urethra (6, 10). These antagonists improve both urinary voiding disorders and urinary collecting disorders, while coadministration of the alpha-1 adrenergic receptor antagonist and the anti-muscarinic agent is more effective for controlling overactive bladder (OAB) in BPH patients (3). Anti-muscarinic agents are known to inhibit bladder smooth muscle contraction, and may possibly also block the effects of muscarinic receptors on bladder epithelial cells (12,20). Bladder epithelial cells exhibit a number of properties similar to those of neurons (nociceptors/mechanoreceptors), and both types of cells share several signal transduction mechanisms to detect physiological stimuli. Examples of neuronal sensory receptors that have been identified in the bladder epithelium include receptors for purine (15), noradrenaline (4), and acetylcholine (12, 13). Recent studies have also shown that intravenous administration of alpha-1 adrenergic receptor antagonists inhibits adenosine triphosphate (ATP) release into the bladder lumen as well as bladder afferent nervous activity (9), while application of muscarinic agonists provokes ATP release from cultured bladder epithelial cells (14). These results suggest that both alpha-1 adrenergic receptor antagonist and anti-muscarinic agents inhibit ATP secretion from the bladder epithelium, and

BackgroundThe lack of sufficient specificity and sensitivity among conventional cancer biomarkers, such as prostate specific antigen (PSA) for prostate cancer has been widely recognized after several decades of clinical implications. Autoantibodies (autoAb) among others are being extensively investigated as potential substitute markers, but remain elusive. One major obstacle is the lack of a sensitive and multiplex approach for quantifying autoAb against a large panel of clinically relevant tumor-associated antigens (TAA).MethodsTo circumvent preparation of phage lysates and purification of recombinant proteins, we identified B cell epitopes from a number of previously defined prostate cancer-associated antigens (PCAA). Peptide epitopes from cancer/testis antigen NY-ESO-1, XAGE-1b, SSX-2,4, as well as prostate cancer overexpressed antigen AMACR, p90 autoantigen, and LEDGF were then conjugated with seroMAP microspheres to allow multiplex measurement of autoAb present in serum samples. Moreover, simultaneous quantification of autoAb plus total PSA was achieved in one reaction, and termed the "A+PSA" assay.ResultsPeptide epitopes from the above 6 PCAA were identified and confirmed that autoAb against these peptide epitopes reacted specifically with the full-length protein. A pilot study was conducted with the A+PSA assay using pre-surgery sera from 131 biopsy-confirmed prostate cancer patients and 121 benign prostatic hyperplasia and/or prostatitis patients. A logistic regression-based A+PSA index was found to enhance sensitivities and specificities over PSA alone in distinguishing prostate cancer from nonmalignant cases. The A+PSA index also reduced false positive rate and improved the area under a receiver operating characteristic curve.ConclusionsThe A+PSA assay represents a novel platform that integrates autoAb signatures with a conventional cancer biomarker, which may aid in the diagnosis and prognosis of prostate cancer and others.

Aim : Many patients with stress urinary incontinence do not have enough motivation to continue pelvic floor muscle training (PFMT) by themselves. Therefore, a device was created to support PFMT, and its effect was examined. Methods : Forty-six women with stress urinary incontinence were assigned to a control group or a device group in order of presentation. A pamphlet on PFMT was given to control patients, while the same pamphlet plus the device and instructions on its use were given to patients in the device group. The device had a chime that was set to sound three times a day when exercise sessions were scheduled. PFMT consisted of fast and slow pelvic floor muscle contraction exercises that were performed for 2 min and followed a rhythm set by the device. Results : After 8 weeks, 20 patients from the control group and 21 patients from the device group could be evaluated. In the control group, only the quality of life (QOL) index improved significantly. In the device group, however, the daily number of incontinence episodes, the number of pads used daily, the QOL index, and the pad weight in the pad test improved significantly. Patients in the device group said that they felt obligated to perform PFMT when the chime sounded. Forty-eight percent of patients from the device group were satisfied with the outcome of PFMT, while only 15% were satisfied in the control group. Conclusion : This device may be useful to support the management of stress urinary incontinence.

Purpose: Carbonic anhydrase 9 (CA9) is the most promising molecular marker described for renal cell carcinoma (RCC) to date. We investigated whether transduction of monocytes from peripheral blood with adenovirus encoding the CA9 gene (AdV-CA9) could stimulate a T-cell mediated immune response against cancer cells expressing CA9. The ability to consistently generate a T-cell response is an important step toward the development of a CA9-specific RCC vaccine.Experimental Design: AdV-CA9 was generated using the AdEasy system. AdV-CA9-transduced peripheral blood mononuclear cell (PBMC)-derived monocytes were used to raise CTLs from autologous peripheral blood lymphocytes (PBLs). The ability of CTLs to lyse targets expressing CA9 was assessed by 51 Cr-release. Results: Monocytes were efficiently transduced with AdV-CA9. In five of six experiments, AdV-CA9-transduced monocytes were able to induce a population of CTLs from bulk PBLs. CTLs were capable of lysing autologous, but not allogeneic monocytes expressing CA9. Furthermore, CTLs were able to lyse autologous RCC tumor cells expressing CA9. The ability of CTLs to lyse relevant targets was blocked by anti-CD3, anti-CD8, and anti-MHC class I antibodies demonstrating a MHC class I restricted response.Conclusions: These results suggest that PBMC-derived monocytes transduced with AdV-CA9 can generate RCCspecific MHC class I restricted CTLs capable of lysing CA9-expressing cancer cells. Transduction of PBMCderived monocytes with adenovirus provides a simple and effective alternative to the use of dendritic cells for the induction of antigen-specific CTL.