Nancy Wehner

An analysis of urinary prostate specific antigen before and after radical prostatectomy : evidence for secretion of prostate specific antigen by the periurethral glands

We investigated whether urinary prostate specific antigen (PSA) might be a useful marker to detect locally recurrent tumor after radical prostatectomy. We also investigated whether PSA in the first 1 to 5 cc of voided urine is a more useful indicator of urinary PSA levels than the midstream urine PSA, since the first portion of the voided urine contains the highest concentration of prostatic and urethral secretions. To determine the response of urinary PSA to radical prostatectomy, we obtained first voided and midstream urine PSA levels in 18 patients with adenocarcinoma of the prostate before and after surgery. Mean first voided urine PSA levels decreased from 915.1 ng./ml. (range 21 to 2,853) preoperatively to 21.4 ng./ml. (range 0.9 to 88) postoperatively, while mean midstream urine PSA levels decreased from 245.9 ng./ml. (range 5 to 1,312) preoperatively to 1.8 ng./ml. (range 0 to 20.4) postoperatively. We also obtained postoperative first voided and midstream urine PSA levels in 9 prostate cancer patients who had undergone radical prostatectomy, and were considered to be cured by rigid clinical and histological criteria. To distinguish bladder versus urethral sources of urinary PSA in patients without a prostate, we additionally studied 11 patients without prostate cancer who had undergone cystoprostatectomy with orthotopic bladder substitution and who had undetectable serum PSA levels by the ultrasensitive assay. In the cured prostatectomy patients the mean first voided urine PSA level was 40.2 ng./ml. (range 2.8 to 100) and the mean midstream urine PSA level was 3.4 ng./ml. (range 0.1 to 15.2), while in the cystoprostatectomy patients these levels were 15.5 ng./ml. (range 0.8 to 49.9) and 1.2 ng./ml. (range 0 to 6.4), respectively. We conclude that the first voided urine sample better reflects local PSA production by the prostate than the midstream sample, first voided urine PSA decreases significantly in response to radical prostatectomy but is still present in measurable amounts even in surgically cured prostate cancer patients and urethral secretion of low levels of PSA persists after radical prostatectomy. This finding diminishes the chance that the first voided urine PSA level will be a useful marker to detect locally recurrent tumor after radical prostatectomy. Further studies are needed to determine if there is a critical level of first voided urine PSA after radical prostatectomy above which there is an increased likelihood of locally recurrent tumor but overall urinary PSA is highly unlikely to be clinically useful.

Early detection of residual prostate cancer after radical prostatectomy by an ultrasensitive assay for prostate specific antigen.

We evaluated the usefulness of an ultrasensitive immunoassay for prostate specific antigen (PSA), modified from the standard Yang Pros-Check PSA test and with a biological detection limit for PSA in serum of 0.07 ng./ml., to detect residual prostate cancer at an earlier date. We studied retrospectively serial frozen serum samples from 22 prostate cancer patients after radical prostatectomy who later had residual cancer with detectable PSA levels of 0.3 ng./ml. or more by the standard PSA test. As controls we studied 33 cystoprostatectomy patients (for bladder cancer) without histological evidence of prostate cancer and 23 patients after radical prostatectomy who had the highest probability of cure of the cancer. All control patients without cancer had PSA values (282 of 283 samples, 99.6%) of less than 0.1 ng./ml. This value was called the residual cancer detection limit. In the 22 patients with recurrent cancer the ultrasensitive assay detected cancer recurrence (PSA 0.1 ng./ml. or more) much earlier (median 202 and mean 310 days) than the standard assay (PSA 0.3 ng./ml. or more). On screening 187 current post-radical prostatectomy patients without evidence of cancer by the standard assay the ultrasensitive assay detected 21 (11.2%) with evidence of residual cancer, that is PSA level of 0.1 ng./ml. or more. We conclude that an ultrasensitive assay for PSA can detect residual cancer after radical prostatectomy much earlier than current immunoassays for PSA. Earlier detection of residual cancer may improve long-term survival by allowing for earlier institution of adjuvant therapy.

The immunologic basis of recurrent bacteriuria: role of cervicovaginal antibody in enterobacterial colonization of the introital mucosa.

Collections of cervicovaginal fluid (CVF) and introital and anal canal swabs were obtained from 51 premenopausal 1 postmenopausal and 1 hysterectomized females with recurrent bacteriuria. 10 premenopausal and 3 hysterectomized females who had never experienced urinary infections served as controls. Antibody coating of bacteria was assessed in CVF by the indirect immunofluorescence technique of measuring serum antibody titer. Quantitation of immunoglobulins was achieved by low and ultra low radial immunodiffusion. Cervicovaginal antibody (CVA) as measured by antibody coating of enterobacteriaceae that colonize the vaginal vestibule was found in 26% of subjects susceptible to urinary tract reinfections. 77% of control subjects resistant to urinary infections demonstrated antibody-coating of the fecal Enterobacteriaceae when exposed to CVA suggesting that absence of vaginal colonization in normal women is related to CVA against their own fecal bacteria. O-groups specificity of CVA to fecal E. coli in control subjects was suggested by the poor response of CVA to serogroups OX9 and 0103. Lactobacilli and S. epidermidis never coated with CVA. Specific vaginal antibody to Enterobacteriaceae was found in the absence of the cervix and uterus. The most common antibody in CVF was IgA but IgG was almost as frequent. IgM was detected in nearly half the control patients.

Physiologic (intraindividual) variation of serum prostate-specific antigen in 814 men from a screening population*

OBJECTIVES We measured the intraindividual variation of prostate-specific antigen (PSA) in the serum of healthy men screened for prostate cancer. METHODS We used a fully automated PSA assay system (ACS: 180 assay) to evaluate a screening population of 814 men (mean age, 63.3 years; range, 50 to 79 years) without documented prostate cancer or prostate surgery. A second blood sample was drawn 15 to 183 days after the first specimen (mean, 80 days). RESULTS In the ACS PSA ranges of 0 to 7.2 ng/mL, 7.3 to 17.9 ng/mL, and 18.0 ng/mL or greater (O to 4 ng/mL, 4 to 10 ng/mL, and 10.0 ng/mL or greater by the Tandem-R assay), the mean coefficient of variation of the first and second blood drawn was 20%, 12%, and 10%, respectively. In 435 men whose first blood samples were measured twice for PSA difference (interassay or run-to-run variation), the intraindividual variation in the range of 0 to 7.2 ng/mL was significantly larger than the interassay variation, which was also true the 7.3 to 17.9 ng/mL range. In the range of 0 to 7.2 ng/mL, 251 of 695 (36%) showed a 20% or greater relative increase and 69 of 695 (10%) showed a 1.3 ng/mL (0.75 ng/mL by the Tandem-R assay) or greater absolute increase of PSA at the second blood sample. CONCLUSIONS We conclude that in the low ranges of PSA concentrations, one should consider the possibility of substantial intraindividual variation when interpreting serial PSA measurements.

Urinary Polyamine Levels in the Diagnosis of Carcinoma of the Prostate

Urinary excretion of the basic polyamine, spermidine, was significantly elevated in patients with prostatic carcinoma as compared to a control group of patients, Of 44 urine specimens from patients with prostatic malignancy 31 had spermidine levels more than 2 mg. per 24 hours, while only 3 of 13 urine specimens from the control groups had levels in excess of this value. The increase in spermidine appeared to be correlated with the histologic grading of the tumor, that is 30 of 34 specimens from patients with grade II, III or IV carcinoma had excessive spermidine excretion and only 1 of 10 urine specimens from patients with grade I tumors had similiar spermidine elevations. High spermidine levles were found in tumors localized to the prostate and in 7 of 8 patients with negative pelvic and para-aortic lymph node biopsies. This study raises the possibility that urinary spermidine determinations may aid in the development of a biochemical screening test for prostatic neoplasms.

The Detection of a Local Prostatic Immunologic Response to Bacterial Prostatitis

Although local antibody responses at bronchial, pulmonary and intestinal surfaces have been studied previously a similar response from the prostatic surface has never been described. This investigation demonstrates a distinct local antibody response in the prostatic fluid of 2 patients with bacterial prostatitis. Levels of antigen-specific and total non-specific immunoglobulins A and G were measured at intervals during and following infection for at least 2 years. These studies show that local prostatic immunologic responses are independent of serum responses and specific for the infecting organism. Furthermore, local secretory immunoglobulin A is the predominant immunoglobulin involved in the response to prostatic infection. Serum antigen-specific antibody and total serum or prostatic fluid immunoglobulin measurements are in adequate reflections of the prostatic immune response.

The characterization of bacterial and nonbacterial prostatitis by prostatic immunoglobulins.

Although inflammatory diseases of most human secretory surfaces are difficult to investigate clinically, the secretory immune system of the human prostate may be studied relatively easily because prostatic fluid may be obtained from the gland by digital massage. We studied inflammatory conditions of the prostate to establish whether we could use the humoral immune response to differentiate these conditions. Using a sensitive solid-phase radioimmunoassay, we measured total IgA and IgG, and IgA and IgG antibodies to Enterobacteriaceae in the serum and prostatic fluid of men with and without prostatic inflammation. These studies show that levels of IgA and IgG in the prostatic fluid of men with bacterial prostatitis are higher than those in men without histories of urinary or prostatic infections. In men with bacterial prostatitis, prostatic antibodies to Enterobacteriaceae were elevated 12 to 18 months after curative treatment and indefinitely after ineffective treatment; anti-Enterobacteriaceal IgG levels returned to normal after infection only with cure. Total IgA and IgG in the prostatic fluid of men with nonbacterial prostatitis--men who have signs of prostatic inflammation without evidence of old or ongoing bacterial infection--are also higher than levels found in uninfected individuals. Although this finding supports an inflammatory etiology for the symptoms seen in nonbacterial prostatitis, no significant IgA or IgG Enterobacteriaceal antibody titers were detected in these patients. This excludes a remote Enterobacteriaceal infection as a cause of nonbacterial prostatitis. These observations confirm that the prostate gland is a distinct part of the male secretory immune system.

The Diagnostic Value of the Immunologic Response in Bacterial and Nonbacterial Prostatitis

Using a solid-phase radioimmunoassay that permits quantitation of specific antibodies to infecting bacteria in the prostatic fluid of patients with bacterial prostatitis we measured the immunologic response to common gram-negative urinary pathogens in 6 patients with bacterial prostatitis, 4 with nonbacterial prostatitis and 10 normal volunteer controls. The results show that true bacterial prostatitis is clearly distinguishable immunologically from nonbacterial inflammation of the prostate. Normal volunteer controls, like patients with nonbacterial inflammation of the prostate, have no antigen-specific antibodies to gram-negative urinary pathogens in the prostatic secretion. In clinical situations when bacteriologic localization data are confusing, immunologic analysis provides a specific tool for definitive diagnosis. Data from bacterial absorption studies show that antigen-specific antibodies determined by solid-phase radioimmunoassay can be measured in milligrams per deciliter rather than units of dilutional titers. This approximation of antigen-specific antibodies in milligram quantities permits a more quantitative approach to understanding surface mucosal immunity in terms of the class-specific immunologic response.

Use of a solid-phase radioimmunoassay and formalin-fixed whole bacterial antigen in the detection of antigen-specific immunoglobulin in prostatic fluid.

The prostatic fluid of two patients with Escherichia coli bacterial prostatitis was analyzed for evidence of a local immune response to bacterial infection. A solid-phase radioimmunoassay was modified to measure the immunoglobulin (Ig)A and IgG antigen-specific antibody responses to infecting bacteria in serum and prostatic fluid from patient. Formalin-fixed whole E. coli were used as antigen. In one patient with acute E. coli prostatic infection, measurements of antigen-specific antibody confirm the presence of a systemic and local immune response. However, in another patient with a chronic E. coli prostatitis, a primarily local immune response was demonstrated. The response measured in the prostatic fluid appears to be locally stimulated and specific for the infecting bacteria. Furthermore, IgA was the predominant immunoglobulin involved in the local prostatic immune response to infection. Although elevations of serum IgA antigen-specific antibody levels were short-liver after treatment of prostatic infection, local IgA antigen-specific antibodies were detected for as long as 1 yr after the initial infection in both patients studied.

The purification and assay of the prostatic antibacterial factor (PAF)

Abstract Human seminal plasma and canine prostatic fluid have a potent bactericidal effect. The compound responsible for the activity, the prostatic antibacterial factor (PAF), purified approximately 5000-fold by ion-exchange chromatography on a Dowex 50WX2 H + resin, is a heat stable, water soluble, low molecular weight cationic substance. About 90% of the organisms commonly responsible for human urinary tract infections are sensitive to this antibacterial agent. Preliminary results indicate that PAF may play an important role as a defense mechanism in humans. PAF activity was demonstrated in the seminal plasma of 34 human controls tested. In 6 patients with chronic bacterial prostatitis PAF activity was either absent or markedly reduced.