Variation of free and total prostate-specific antigen levels: the effect on the percent free/total prostate-specific antigen.

OBJECTIVE: Recent studies have shown that calculations of the percent free/total prostate-specific antigen (PSA) improves the specificity of PSA testing. Characterizing the variability of free PSA and total PSA is necessary to evaluate the utility of an isolated free/total PSA measurement. We investigated the total variation of free and total PSA levels to determine how the percent free/total PSA was affected. DESIGN: Serum was obtained from nine urological patients on 5 different days over a 2-week period. Free and total PSA levels were measured on the day of collection. The total variation expressed in terms of percent coefficient of variation (%CV) was calculated, and the biological variation was derived taking analytical variation into consideration. SETTING: Patients were from Seattle (Wash) Urological Associates, and samples were processed at the Dynacare Laboratory of Pathology, Seattle, Wash. PATIENTS: Nine men (aged 48 to 69 years) were evaluated; three had been diagnosed with prostate cancer, three with benign prostatic hyperplasia, one with chronic prostatitis, one with high-grade prostatic intraepithelial neoplasia, and one was clinically normal. MAIN OUTCOME MEASURES: Total variation for free, total, and percent free/total PSA. RESULTS: The average total variation was 13.9% CV, 7.5% CV, and 10.6% CV for free, total, and percent free/ total PSA, respectively. Biological variation was derived to be 13.0% CV, 5.6% CV, and 8.0% CV for free, total, and percent free/total PSA, respectively. CONCLUSIONS: When applied, these results suggest that there are significant random changes in the numerator and denominator of the free PSA-total PSA ratio that could result in clinical misinterpretation. Clinicians must be aware that free PSA and total PSA levels will fluctuate owing to nonpathologic variation.

Hemophilia presenting as compartment syndrome in the arm following venipuncture. A case report and review of the literature.

A three-month-old male infant with undiagnosed hemophilia presented with fever and irritability. During the diagnostic evaluation a venipuncture in the right antecubital fossa led to hemorrhage and a compartment syndrome in the brachium. Differential diagnosis included osteomyelitis and septic arthritis but a 99technetium bone scan revealed only delayed washout of radioactive material from the right brachium without increased uptake. Despite elevated pressures in the muscle compartments of the right arm, surgical decompression was delayed until a complete blood coagulation profile was obtained. After replacement of deficient blood products, the compartment syndrome resolved without surgical decompression. Defective coagulation leading to hemorrhage into the muscle compartments of the arm resulted in a significant elevation of compartmental pressure. The unusual clinical presentation of the patient, as well as a lack of a positive family history, delayed the diagnosis of hemophilia and the subsequent replacement therapy.

Differences in prostate size between patients from University and Veterans Affairs Medical Center populations.

BACKGROUND: Numerous studies on prostatic disease have been performed at Veterans Affairs (VA) Medical Centers. Recent investigations evaluating early detection of prostate cancer provide insight that the average prostate volume may be different between patients with similar clinical findings who are from different hospital settings. The objective of this study was to compare prostate size between men from University and VA Medical Centers. METHODS: Patients were enrolled retrospectively from 1989-1996 from the Urology Clinics at a University and a VA Medical Center. All men underwent transrectal ultrasound-guided sextant biopsy of the prostate owing to either an elevated prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE) detected prior to biopsy. Prostate volume was calculated using the ellipsoid three-diameter formula based on transrectal ultrasound measurements. RESULTS: There were 1,311 men included in the analysis: 717 were from the VA, and 594 were from the University. The average prostate volume was significantly smaller among VA patients both for men with cancer (P = 0.0004) and for men with no evidence of malignancy (P < 0.0001). Overall, the average prostate volume was 38.5 cm3 (median, 32.5 cm3) among men from the VA compared to 46.8 cm3 (median, 39.3 cm3) among men from the University Medical Center. Men from the VA were older (mean +/- SD = 68 +/- 7.3) than men from the University (mean +/- SD = 66 +/- 7.7) (P = 0.004) and there was no significant difference in PSA levels between the two groups of patients (P = 0.11). Intriguingly, the incidence of cancer was significantly lower at the VA (24.5%) compared to the University (35.9%) (P < 0.0001). CONCLUSIONS: The variance in prostate size suggests that there are significant differences between the two patient populations. Proposed factors leading to this discrepancy include differences in socioeconomic factors, environmental factors, and changes in hormonal milieu related to alcohol and tobacco use. These results may have significant implications regarding the interpretation and extrapolation of results from previous studies performed at a single hospital setting.

Reconstitution of the patellar tendon donor site after graft harvest.

Little is known about the fate of the donor site after the central 1/3 of the patellar tendon is harvested for anterior cruciate ligament reconstruction. This study evaluated the donor site in the patellar tendon at various times after a graft from the central 1/3 of the patellar tendon was harvested. Fourteen patients were studied with magnetic resonance images taken from 6 weeks to 2 years after anterior cruciate ligament reconstruction. Axial, sagittal, and coronal views of the patellar tendon were obtained. A second group of 8 patients who had previous anterior cruciate ligament reconstruction were returned to the operating room for subsequent procedures on the affected knee. These procedures were performed 2 to 24 months after the original reconstruction. An open biopsy was obtained from the donor site in the patellar tendon. On magnetic resonance images, the size of the defect and the intensity of the signal in the central 1/3 of the tendon decreased with time from surgery. At 2 years, the defect was indistinguishable from normal tendon. Histologically, the scar in the defect progressively matured with time, becoming nearly identical to normal tendon at 2 years.

Comparison of 3 investigational assays for the free form of prostate specific antigen.

PURPOSE: Measuring percent free/total prostate specific antigen (PSA) versus total PSA alone has been shown to enhance the stratification of cases with and without prostate cancer. We compared the diagnostic performance of 3 free PSA assays when values were interchanged over a common total PSA denominator. MATERIALS AND METHODS: Archival sera from 123 consecutively accrued patients (25 with prostate cancer, 98 with no evidence of malignancy) who had pre-biopsy total PSA levels from 2.0 to 20.0 ng./ml. were obtained from our specimen bank. Serum specimens were analyzed using the Hybritech Tandem R, Dianon Systems and Chiron ACS 180 free PSA assays. Total PSA was measured using the Hybritech Tandem R total PSA assay. Linear regression was performed to evaluate the correlation and agreement among assays. Sensitivity and specificity of cancer detection were calculated to compare diagnostic performance. RESULTS: The required percent free PSA cutoffs were different among the 3 free PSA assays. The cutoffs to ensure a 95% sensitivity of cancer detection were 22, 34 and 34%, and the number of negative biopsies that were prevented at these cutoffs (specificity) was 38, 19 and 33% for the Hybritech, Dianon, and Chiron assays, respectively. CONCLUSIONS: The results among the different assays were not interchangeable. Clinicians should be aware that different percent free PSA cutoffs need to be used based on the type of free and total PSA assays, and that not all assays diagnostically perform the same.

Biological variation of prostate specific antigen levels in serum: an evaluation of day-to-day physiological fluctuations in a well-defined cohort of 24 patients.

PURPOSE: We evaluated the daily biological variation of serum prostate specific antigen (PSA) concentrations to determine the critical difference required between 2 consecutive PSA measurements that would indicate a significant elevation. MATERIALS AND METHODS: A total of 24 men, grouped according to clinical diagnosis and PSA, underwent phlebotomy for 10 consecutive weekdays. Duplicate serum samples were measured using 3 separate lots of Tandem-E and IMx PSA assays. The biological variation was calculated and the 2 PSA assay systems were compared. The critical difference was examined to determine the percent elevation necessary to indicate (with 95% confidence) that PSA had increased beyond what would be expected from biological and analytical variation. RESULTS: The biological variation, defined in terms of percent coefficient of variation, had a log-normal distribution with a geometric mean of 7.3% coefficient of variation and a 95th percentile value of 19.2% coefficient of variation using the Tandem-E PSA assay. Assuming an analytical variation of 5% coefficient of variation, the median critical difference was 20.5% and the 95th percentile critical difference was 45.8%. There was no significant difference between the 2 PSA assay systems in biological variation. However, PSA concentrations measured by the IMx assay were consistently lower compared to values measured by the Tandem-E assay. CONCLUSIONS: Characterizing the biological variation of serum PSA assists in evaluating the significance of changes in serial PSA measurements. The degree of biological variation differs among patients, such that an increase between 2 consecutive PSA levels that is less than 20 to 46% may be due to biological and analytical variation. These data influence interpretation of repeated measurements of serum PSA with time.

Day to day changes in free and total PSA: significance of biological variation.

In this study we evaluated the physiological variation of free and total prostate-specific antigen (PSA) levels to determine how the percent free/total PSA was affected. Twenty four patients had blood drawn for ten consecutive weekdays. The percent coefficient of variation (%CV) of biological variation was calculated. The results were log-normally distributed with geometric means of 12.0% CV, 7.3% CV, and 8.8% CV for free, total, and percent free/total PSA, respectively. When applied, the percent free/total, PSA would need to fluctuate by 31% to indicate that a significant change (critical difference, P<0.05) between two measurements had occurred. Biological variation of PSA measurements is substantial.