A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result.

BACKGROUND: New screening methods that can add predictive diagnostic value for aggressive (high-grade, Gleason score ⩾ 7) prostate cancer (PCa) are needed to reduce unnecessary biopsies for patients with non-aggressive PCa. This is particularly important for men presenting for an initial biopsy with an equivocal PSA in the 2-10 ng ml(-1) range. PCA3 and ERG are biomarkers that can add predictive value for PCa in urine; however, with a limited utility as a digital rectal exam (DRE) is required. METHODS: First-catch urine samples were collected at six sites from men scheduled to undergo a prostate biopsy. Exosomal RNA was extracted, RNA copy numbers of ERG and PCA3 were measured by reverse transcription-quantitative PCR (RT-qPCR), and the EXO106 score (the sum of normalized PCA3 and ERG RNA levels) was computed. Performance was compared with standard of care (SOC; PSA, age, race or family history) parameters. Contingency table, logistic regression, receiver operating characteristics curve and box-plot analyses were performed. RESULTS: In this cohort (N=195), a dichotomous EXO106 score demonstrated good clinical performance in predicting biopsy result for both any cancer and high-grade disease. For high-grade disease, the negative and positive predictive values were 97.5% and 34.5%, respectively. The discrimination between high-grade and Gleason score ⩽ 6 (including benign) biopsy results by a combination of EXO106 and SOC (area under the curve (AUC)=0.803) was significantly improved compared with SOC without EXO106 (AUC=0.6723, P=0.0009). The median EXO106 score correlated (P<0.001; Spearman's rank order) with histologic grade. CONCLUSIONS: A novel molecular signature (EXO106 score) derived from non-DRE urine demonstrated independent, negative predictive value for the diagnosis of high-grade PCa from initial biopsy for men with 'gray zone' serum PSA levels. Its use in the biopsy decision process could result in fewer prostate biopsies for clinically insignificant disease.

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.

Extracorporeal shock wave lithotripsy. Use of antibiotics to avoid postprocedural infection.

Extracorporeal shock wave lithotripsy (ESWL) has the potential to revolutionize the treatment of urolithiasis, but its success depends in part upon minimizing potential sequelae. Although ESWL is safe, effective, and relatively economical, one complication can be urosepsis, resulting from liberation of bacteria when the stones disintegrate. Patients who are at increased risk of infection are those who have existing urinary tract infection; perioperative urologic manipulation; infected stones; predisposition for infectious endocarditis; or multiple, large, or complex stones. If urosepsis occurs, it usually requires prolonged hospitalization, which obviates any cost-benefits that can be accrued from ESWL. Prophylactic use of an antibiotic before ESWL is rational and cost-effective. Ideally, the antibiotic should possess a spectrum of activity against the most likely bacteria to be encountered, require a limited number of doses, and offer the flexibility of sustained coverage in the event that the procedure is delayed. Our experience at Presbyterian Hospital of Dallas supports the use of a long-acting cephalosporin for the prevention of infections following ESWL.

Principles and application of extracorporeal shock wave lithotripsy.

The physics, instrumentation, and patient-care aspects of extracorporeal shock wave lithotripsy (ESWL) in the treatment of kidney stone disease are described. The kidney stone is located through the use of two integrated roentgenographic imaging systems. The x-ray tubes, fixed on either side of a tub of water in which the patient is partially immersed, are directed upward. The patient is maneuvered until the imaging systems indicate the kidney stone is within the second focus of the reflector and within the 1.5-cu cm target area. Once within this alignment, the stone is ready for shock wave treatment; general or regional anesthesia is used to immobilize the patient so that the position of the stone can be maintained within the focus of the shock wave. When the stone is repeatedly subjected to this high-energy force, it begins to disintegrate until fragments of less than 1 mm are left. ESWL can (1) disintegrate kidney stones of all types, (2) be efficiently transmitted over distances that allow the shock wave source to be outside the body, (3) safely pass through living tissue, and (4) be precisely controlled and focused into a small target area. ESWL is a safe, effective, and cost-saving treatment that can be used for 90% of all kidney stone disease that previously required surgery.

Private practice experience with radical surgical treatment of cancer of prostate.

This private practice series of 255 men with adenocarcinoma of the prostate was evaluated with regard to the efficacy of radical prostatectomy in controlling disease. Sixty-seven men underwent radical surgery: 77 per cent are surviving longer than ten years post-operatively with several of these individuals now in their fifteenth year, 9 per cent died of their disease, and 10 per cent are totally incontinent. The survival in this series are compared with those of other series and the differences discussed.

A private practice experience with adenocarcinoma of the prostate in men less than 50 years old.

We have found a sharp increase in the number of men less than 50 years old with adenocarcinoma of the prostate. In the last 4 years we have found 9 new patients less than 50 years old, which far exceeds the expected number. Prompted by this increase we reviewed our experience with prostatic carcinoma in young men. Our findings of 11 of 256 patients (4 per cent) and good survival from 6 months to 15 years (90 per cent) are at variance with previously published reports. We attribute the increased number of patients with adenocarcinoma of the prostate to our willingness to biopsy small "unimportant" nodules in the prostate. Whether these findings reflect an actual increase in the incidence of prostatic carcinoma in young men or simply an increase in the frequency of diagnosis of previously unrecognized lesions is not clear.

Serum alpha-fetoprotein and human chorionic gonadotropin in patients with seminoma.

We analyzed the case histories of 31 patients who initially had a diagnosis of seminoma and elevated serum levels of alpha-fetoprotein or human chorionic gonadotropin. We concluded that an elevated alpha-fetoprotein level is firm evidence of the presence of non-seminomatous germ cell tumor and that the patient should be treated accordingly. However, if the level of human chorionic gonadotropin alone is elevated the diagnosis may be either non-seminomatous tumor or seminoma. Patients with seminoma and an elevated level of human chorionic gonadotropin do respond well to radiation therapy if they have low stage disease but if metastatic seminoma is present an elevated human chorionic gonadotropin level appears to be a poor prognostic sign if conventional treatment is given. A plan of treatment is proposed for these patients.

The seminoma decoy: measurement of serum human chorionic gonadotropin in patients with seminoma.

Serum human chorionic gonadotropin levels were determined in 20 patients with histologically proved seminoma. The test was positive in 2 of the 20 patients and was predictive of non-seminomatous metastasis in each case. Serum human chorionic gonadotropin is a useful tumor marker in detecting and following non-seminomatous metastases in men with pure seminoma of the testis.

The endocrinology of human chorionic gonadotropin-secreting testicular tumors: new methods in diagnosis.

Serum from 59 men with testicular masses was examined for the presence of human chorionic gonadotropin-beta. Results indicate: 1) In patients with testicular tumor human chorionic gonadotropin-beta serves as a sensitive and specific marker of tumor activity with an incidence of 28%. 2) Because human chorionic gonadotropin-beta levels correlate with response to therapy this test will be useful in selecting men for adjunctive irradiation or chemotherapy. 3) Radioimmunoassay for human chorionic gonadotropin-beta is far more sensitive and specific than conventional methods for detecting human chorionic gonadotropin production. 4) After unilateral orchiectomy for carcinoma of the testis elevated serum luteinizing hormone levels are common and may be unrelated to the presence or activity of residual tumor. 5) Human chorionic gonadotropin-beta-producing tumors were associated with increased estradiol and testosterone levels and significantly depressed serum follicle stimulating hormone levels in this series. 6) The prognostic implications of the presence of human chorionic gonadotropin-beta are not yet fully understood. The importance of this study is the fact that men with testicular tumors have a high incidence of human chorionic gonadotropin-beta secretion and this fact provides the physician with a powerful new tool for examining the various aspects of tumor activity. It also shows the feasibility for prospective screening of patients with a wide variety of neoplasms of differing histologic types.