MicroRNA profile analysis of human prostate cancers.

We examined the microRNA (miRNA) expression profile of 40 prostatectomy specimens from stage T2a/b, early relapse and non-relapse cancer patients, to better understand the relationship between miRNA dysregulation and prostate oncogenesis. Paired analysis was carried out with microdissected, malignant and non-involved areas of each specimen, using high-throughput liquid-phase hybridization (mirMASA) reactions and 114 miRNA probes. Five miRNAs (miR-23b, -100, -145, -221 and -222) were significantly downregulated in malignant tissues, according to significance analysis of microarrays and paired t-test with Bonferroni correction. Lowered expression of miR-23b, -145, -221 and -222 in malignant tissues was validated by quantitative reverse transcription (qRT)-PCR analyses. Ectopic expression of these miRNAs significantly reduced LNCaP cancer cell growth, suggesting growth modulatory roles for these miRNAs. Patient subset analysis showed that those with post-surgery elevation of prostate-specific antigen (chemical relapse) displayed a distinct expression profile of 16 miRNAs, as compared with patients with non-relapse disease. A trend of increased expression (>40%) of miR-135b and miR-194 was observed by qRT-PCR confirmatory analysis of 11 patients from each clinical subset. These findings indicate that an altered miRNA expression signature accompanied the prostate oncogenic process. Additional, aberrant miRNA expression features may reflect a tendency for early disease relapse. Growth inhibition through the reconstitution of miRNAs is potentially applicable for experimental therapy of prostate cancer, pending molecular validation of targeted genes.

Disappointing initial results with transurethral alprostadil for erectile dysfunction in a urology practice setting.

PURPOSE: We evaluate the response to intraurethral alprostadil administration using the Medicated Urethral System for Erection (MUSE) in unselect men with a history of erectile dysfunction. We determine the effects on blood pressure during in office monitoring and assess safety of this form of treatment. We compare the efficacy of MUSE in an office setting with the placebo controlled pivotal study. MATERIALS AND METHODS: A total of 115 men with erectile dysfunction underwent in office testing with MUSE following the algorithm recommended by the manufacturer and outlined in the original pivotal study. Patients were asked to rate the rigidity of erection from 1 to 5 with scores 4 and 5 for erections sufficient for intercourse, and level of discomfort from 1 (very uncomfortable) to 5 (very comfortable) at 15-minute intervals. Patients who did not achieve a sufficient erection were scheduled to return for in office testing using the next higher dose up to 1,000 microg. Patient supine and sitting blood pressures were recorded by a nurse before and every 15 minutes after administration. Telephone contact with patients 2 to 3 months after the last in office testing was made to determine whether they were using the system. RESULTS: Mean plus or minus standard deviation rigidity scores independent of dosage increased from 2.34+/-0.99 at 15 minutes to 2.49+/-0.96 at 30 minutes and decreased thereafter. Although the 1,000 microg. dosage resulted in highest mean score at all times, the differences between dosages were not significant. Rigidity score 4 or 5 was achieved in 13.2% (500 microg.) and 30% (1,000 microg.) of patients at 30 minutes. Mean level of discomfort was 3.6+/-1.2 at 15 minutes and improved thereafter. Comfort levels were not significantly different among dosages. Overall, at 15 minutes 16.8% of patients were uncomfortable (score 1 or 2) and 41.3% were somewhat uncomfortable (1, 2 or 3). For all dosages supine and sitting systolic and diastolic blood pressures decreased significantly from before treatment to 15 minutes and stayed lower during monitoring. Defined by strict criteria 41.2% of patients experienced orthostatic hypotension during in office testing. A total of 21 patients had adverse events, including pain, discomfort and burning in the penis (the most common), dizziness and chest pain. One patient had a syncopal episode and fell in the office. At last followup only 18.6% of the tested patients continued to use MUSE at home, while the remainder discontinued treatment due to pain, insufficient erections for intercourse and cost. CONCLUSIONS: We were unable to achieve similar results to the pivotal study following manufacturer instructions and the algorithm provided by that study. Independent of age and etiology no more than 30% of patients at any given time using any dose achieved erections sufficient for intercourse during in office testing. Because of this limited efficacy, discomfort, pain and burning associated with treatment, and cost, more than 80% of patients did not continue to use MUSE at home.

Bilateral multifocal renal oncocytoma: case report and review of the literature.

We report an unusual case of bilateral multifocal renal oncocytoma. The patient underwent bilateral enucleation of 4 tumors of the right and 4 tumors of the left kidney. Frozen section and permanent pathological diagnosis was renal oncocytoma for all tumors. Only 5 other cases of bilateral multifocal oncocytoma have been reported in the literature, of which only 2 had pathological confirmation of the diagnosis. It is important to recognize the potential for multicentric bilateral oncocytomas and to attempt a renal sparing approach in these cases. However, we performed enucleation of all large lesions due to the documented coexistence of renal oncocytoma and renal cell carcinoma as separate simultaneous lesions.

A comparison of renal damage induced by varying modes of shock wave generation.

To evaluate for the possible differences in the extent of pathologic injury occurring following treatment with various lithotripsy modalities, we subjected rabbits to treatment on either an electrohydraulic, electromechanical, or piezoelectric lithotripter. Functional evaluations by enzymuria failed to reveal any difference in the extent of damage between the lithotripters. Pathologic evaluation of the kidneys revealed that both electrohydraulic and electromechanical lithotripsy resulted in an increased instance of acute subcapsular hematoma and fibrosis when compared to piezoelectric treated kidneys (p less than 0.001). Despite the definitive differences noted in the acute animals, there was no significant variation in the area of permanent renal damage that occurred between the various lithotripters.

The role of transabdominal ultrasound in the preoperative evaluation of patients with benign prostatic hypertrophy.

We evaluated 59 consecutive patients for obstructive voiding symptoms with physical examination, excretory urography, urethrocystoscopy, post-voiding residual volumes, uroflowmetry and transabdominal ultrasound of the prostate. Of the patients 53 underwent transurethral resection of the prostate and 6 underwent open prostatectomy. Followup uroflowmetry was done 4 weeks postoperatively. The best predictor of the actual prostatic weight was transabdominal ultrasound (r equals 0.975), and with digital rectal examination and urethrocystoscopy there was a tendency to overestimate small and underestimate large glands. Symptoms such as nocturia do not allow any conclusions about the size of the prostate. The correlation between post-void residual and specimen weight also is poor and only patients in retention (Foley catheter) have a significantly larger prostate. Preoperative uroflowmetry provides limited information about the prostatic size but, although the difference between the preoperative and postoperative flow rate index is highly significant (p less than 0.001, mean difference test), the correlation between specimen weight, and the difference between preoperative and postoperative flow rate index is not significant. We recommend transabdominal sonography of the prostate, a simple and noninvasive procedure, as a useful adjunct in the preoperative evaluation of patients with benign prostatic hypertrophy. In addition to the fact that only this method provides reliable and reproducible estimations of the weight of the prostate, further information, such as measurement of the post-void residual volume, can be obtained without additional costs or loss of time.