J. Yuan

Measurement of prostate-specific antigen in serum as a screening test for prostate cancer

BACKGROUND Prostate-specific antigen (PSA) is secreted exclusively by prostatic epithelial cells, and its serum concentration is increased in men with prostatic disease, including cancer. We evaluated its usefulness in the detection and staging of prostate cancer. METHODS We measured serum PSA concentrations in 1653 healthy men 50 or more years old. Those with PSA values greater than or equal to 4.0 micrograms per liter then underwent rectal examination and prostatic ultrasonography. Ultrasound-directed prostatic needle biopsies were performed in the men with abnormal findings on rectal examination, ultrasonography, or both. The results were compared with those in 300 consecutively studied men 50 or more years old who underwent ultrasound-directed biopsy because of symptoms or abnormal findings on rectal examination. RESULTS Serum PSA levels ranged from 4.0 to 9.9 micrograms per liter in 6.5 percent of the 1653 men (107). Nineteen of the 85 men in this group (22 percent) who had prostatic biopsies had prostate cancer. Serum PSA levels were 10.0 micrograms per liter or higher in 1.8 percent of the 1653 men (30). Eighteen of the 27 men in this group (67 percent) who had prostatic biopsies had cancer. If rectal examination alone had been used to screen the men who had biopsies, 12 of the 37 cancers (32 percent) would have been missed. If ultrasonography alone had been used to screen these men, 16 of the 37 cancers (43 percent) would have been missed. Serum PSA measurement had the lowest error rate of the tests, and PSA measurement plus rectal examination had the lowest error rate of the two-test combinations. CONCLUSIONS The combination of measurement of the serum PSA concentration and rectal examination, with ultrasonography performed in patients with abnormal findings, provides a better method of detecting prostate cancer than rectal examination alone.

T-Cell Subsets Required for Intravesical BCG Immunotherapy for Bladder Cancer

Intravesical bacille Calmette-Guérin (BCG) has been shown in prospective randomized clinical trials to be the treatment of choice for superficial bladder cancer. In this investigation we evaluated the role of CD4 and CD8 lymphocytes in the antitumor response. Monoclonal antibodies to thy 1.2, CD8, CD4 and an isotype control were injected intravenously to deplete T cell populations. After depletion (verified by flow cytometry), BCG therapy was initiated. The results demonstrate that the depletion of either CD4 or CD8 T cell subsets eliminated BCG-mediated antitumor activity. Footpad delayed type hypersensitivity (DTH) was aborted only in CD4 depleted mice; it was essentially unchanged in CD8 depleted mice. However, the presence of DTH was not sufficient for induction of BCG-mediated antitumor activity. Exogenous IL-2 at levels sufficient to induce lymphokine activated killer cell activity did not substitute for CD4 cells. There was no evidence for the induction of protective immunity to the tumor after BCG therapy. These results demonstrate the requirement for T lymphocytes in BCG-mediated antitumor activity and further demonstrate that the presence of both CD4 and CD8 subsets are required. CD8 depletion experiments suggest that the presence of CD4-mediated DTH is not sufficient for the induction of antitumor activity. Furthermore, these data suggest that BCG-mediated antitumor activity is a localized phenomenon that does not induce protective immunity.

Effects of rectal examination, prostatic massage, ultrasonography and needle biopsy on serum prostate specific antigen levels

Measurement of serum prostate specific antigen (PSA) is commonly used to evaluate the prostate gland in a variety of clinical settings. We examined the effects of prostatic manipulations, including digital rectal examination, prostate massage, transrectal ultrasonography and transrectal needle biopsy, on serum PSA levels in 199 men. We detected no clinically significant difference between serum PSA levels obtained immediately before and at 5 or 90 minutes after rectal examination in 43 men. We observed falsely increased PSA levels (to greater than 4 ng./ml., Tandem-R) in 1 of 17 men (6%) following prostatic massage and in 3 of 27 men (11%) following ultrasonography. Transrectal needle biopsy caused an immediate increase in serum PSA in 92 of 100 men. In 29 of these 92 men (32%) when followed weekly serum PSA levels did not return to baseline as expected according to the published serum PSA half-life of 2 to 3 days. Biopsies taking 3 or fewer cores (7 patients) resulted in a smaller increase in serum PSA (mean 1.63 +/- 1.12 times the baseline level versus 6.24 +/- 1.10 times baseline, p less than 0.03) and a proportionally shorter duration of PSA elevation (mean 1.43 +/- 0.48 weeks versus 2.13 +/- 0.14 weeks, p = 0.20) than those taking 4 or more cores (93 patients). Prostate size and the presence of cancer had no influence on the duration of PSA elevation following biopsy. We conclude that digital rectal examination, prostatic massage and ultrasonography have minimal effects on serum PSA levels in most patients. However, prostatic needle biopsy usually causes marked elevations of serum PSA levels with a persistent PSA leak into the blood stream lasting longer than expected from the serum half-life of PSA in approximately 25% of the patients.

The Ability of Systematic Transrectal Ultrasound Guided Biopsy to Detect Prostate Cancer in Men with the Clinical Diagnosis of Benign Prostatic Hyperplasia

Multiple directed and systematic ultrasound guided biopsies of the prostate were performed in 73 men with the clinical diagnosis of benign prostatic hyperplasia (BPH). Seven men (10%) had prostate cancer. Of the 67 patients with benign biopsies 40 underwent subsequent transurethral prostatectomy and 2 (5%) had prostate cancer. Multiple directed and systematic biopsies of the prostate detected 78% of the nonpalpable prostate cancers diagnosed in the study population. Radical prostatectomy was performed in all 9 men with prostate cancer: there were 3 small organ-confined tumors, 5 large organ-confined tumors and 1 stage C tumor with 1 focus of microscopic capsular penetration. Our results suggest that multiple directed and systematic ultrasound guided biopsies are capable of detecting low volume nonpalpable prostate cancer in men with BPH. However, the exact indication for pre-treatment ultrasound guided biopsy of the prostate in men with symptomatic BPH remains unclear. It may be that use of this modality is most appropriate for patients undergoing pharmacological therapy or balloon dilation of BPH rather than for those undergoing transurethral prostatectomy.

Cystotomy, Temporary Urinary Diversion And Bladder Packing in the Management of Severe Cyclophosphamide-Induced Hemorrhagic Cystitis

Severe hemorrhage from cyclophosphamide-induced cystitis sometimes requires aggressive open management when conventional endoscopic and intravesical therapies have failed. We present 2 patients with intractable hematuria who were managed by open cystotomy, temporary urinary diversion via external ureteral stents, and continuous postoperative bladder packing with gauze and hemostatic agents. Both patients had a dramatic improvement in the hematuria immediately postoperatively and 1 with prolonged followup has no urological disability. We suggest that this procedure be considered for management of severe hemorrhagic cystitis as an alternative to more aggressive surgical therapies, such as formal urinary diversion with cystectomy.

A proposed measurement of the ß asymmetry in neutron decay with the Los Alamos Ultra-Cold Neutron Source

This article reviews the status of an experiment to study the neutron spin-electron angular correlation with the Los Alamos Ultra-Cold Neutron (UCN) source. The experiment will generate UCNs from a novel solid deuterium, spallation source, and polarize them in a solenoid magnetic field. The experiment spectrometer will consist of a neutron decay region in a solenoid magnetic field combined with several different detector possibilities. An electron beam and a magnetic spectrometer will provide a precise, absolute calibration for these detectors. An A-correlation measurement with a relative precision of 0.2% is expected by the end of 2002.