Psa
Content
왗your lab focus 왘
Thyroid Goiter, Nodules, and
Thyroid Cancer
Enlargement of the thyroid gland
(goiter), which is common, can be diffuse
or consist of 1 or more nodules. Because
any type of thyroid enlargement can be
associated with normal or altered thyroid
function, a patient with an abnormal thyroid gland should first undergo TSH level
assessment. Patients with hypothyroidism
or hyperthyroidism undergo testing and
are treated as outlined in the previous section. Euthyroid patients with goiters are
usually observed without treatment unless
the goiter itself is causing symptoms.
Euthyroid patients with single, large, or
suspicious nodules should undergo fineneedle aspiration biopsy of the nodule to
rule out cancer. In the past, many benign
goiters and thyroid nodules were treated
with L-T4 suppression therapy, but studies have shown that this is not especially
effective and leads to possible long-term
adverse effects on the heart and bone.
Approximately 5% of thyroid nodules are shown to contain thyroid cancer
at surgery.10 Most cases of thyroid cancer
are best treated with a combination of
surgery, radioactive iodine, and L-T4 therapy. In this case, L-T4 is administered at
doses that suppress TSH to low levels,
since TSH acts a growth factor for thyroid cancer. Patients are observed with
assessment of thyroid hormone levels and
Tg levels and the use of radioactive iodine whole-body scans to detect residual
or recurrent disease.10
1. Schussler GC. The thyroxine-binding proteins.
Thyroid. 2000;10:141-147.
2. Nelson JC, Wilcox RB. Analytic performance of
free and total thyroxine assays. Clin Chem.
1996;42:146-154.
4. Franklyn JA, Black EG, Betteridge J, et al.
Comparison of second and third generation TSH
assays in NTI, hyperthyroidism and in L-thyroxine
treated patients. J Clin Endocrinol Metab.
1994;78:1368-1371.
5. Spencer CA, Wang CC. Thyroglobulin
measurement: techniques, benefits, and pitfalls.
Endocrinol Metab Clin North Am. 1995;24:841849.
6. Burman KD, Pandian R. Clinical utility of assays
for TSH receptor antibodies. Endocrinologist.
1998;8:284-290.
7. Dayan CM, Daniels GH. Chronic autoimmune
thyroiditis. N Engl J Med. 1996;335:99-107.
8. Samuels MH. Subclinical thyroid disease in the
elderly. Thyroid. 1998;8:803-813.
9. Weetman AP. Medical progress: Graves disease. N
Engl J Med. 2000;343:1236-1248.
10. Schlumberger MJ. Papillary and follicular thyroid
carcinoma. N Engl J Med. 1998;338:297-306.
InterNetConnect
American Thyroid Association
<www.thyroid.org>
3. Klee GG. Clinical usage recommendations and
analytic performance goals for total and free
triiodothyronine measurements. Clin Chem.
1996;42:155-159.
interpretation [chemistry]
The Role of Free PSA in the Detection
of Prostate Cancer
Paula C. Southwick, PhD, CCRA, RAC
From the Department of Research and Development, Beckman Coulter, Fullerton, CA
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Increasing test specificity with
determination of percentage of free
prostate-specific antigen (%FPSA)
%FPSA for single cutoff approach
and individual patient risk assessment
%FPSA and staging of prostate
cancer
Comparison of %FPSA to PSA
velocity and age-specific PSA
reference ranges
Detection of Prostate Cancer
With Prostate-Specific Antigen
Prostate cancer is the most common
type of cancer found in men in the
United States, and it is the second leading cause of cancer deaths among
men.1,2 One in 10 men will be diagnosed
with prostate cancer in his lifetime, and
one third will die of the disease.1,2
Historically, the only methods available for the detection of prostate cancer
were digital rectal examination (DRE) and
prostatic acid phosphatase measurement.
Unfortunately, most prostate cancers detected with these methods were at an advanced stage at the time of diagnosis.3-5
In the early 1990s, measurement of
prostate-specific antigen (PSA) in serum
was evaluated for use in the detection of
prostate cancer. PSA, a serine protease, is
produced by both benign and malignant
cells of the prostate. Abnormalities in the
prostate gland architecture resulting from
disease can lead to leakage of PSA into
the bloodstream.
In a large, prospective multicenter clinical trial, PSA and DRE were compared for
effectiveness in prostate cancer detection in
nearly 7,000 men.6 PSA was found to detect more cancers than DRE (82% vs 55%,
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laboratorymedicine> may 2001> number 5> volume 32
respectively); the highest rates of cancer
detection were obtained by using the 2 tests
together. This trial became the basis of the
first PSA test approved by the US Food and
Drug Administration (FDA) for prostate
cancer detection.
PSA testing over time has also contributed to a shift in detection of earlierstage disease, from the historically
observed 70% advanced cancer at diagnosis to the currently observed 30%
advanced cancer.3,7 The National Cancer
Institute recently announced that the
prostate cancer death rate in the United
States declined throughout the 1990s,
providing the first evidence that early detection may decrease mortality rates.
Limitations of PSA Testing
Although PSA is now widely used for
prostate cancer detection, a limitation has
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[F1] Receiver operating characteristic curves for
total prostate-specific antigen (PSA) and
percentage of free PSA (%FPSA). The area under
the curve (AUC) is significantly greater for %FPSA
than for total PSA in men with moderately
elevated PSA concentrations (4-10 ng/mL [4.010.0 ng/mL]). A cutoff of 25% FPSA yields 95%
sensitivity and enhances the specificity of PSA for
prostate cancer screening by sparing 20% of men
with benign disease from unnecessary biopsy.
been its relative lack of specificity when
serum concentrations are moderately elevated (4.0-10.0 ng/mL [4.0-10.0 ng/mL]).
In this range, PSA identifies men as high
risk (25% will have prostate cancer, compared with 4% in the general population of
men over 50 years of age6,8), but specificity
could be improved because within this
PSA range, 75% of biopsy results are negative and unnecessary.
Most patients with prostate cancer
and PSA in this range have early-stage
disease, whereas more than half of the
men with PSA levels above 10 ng/mL (10
ng/mL) have advanced disease.6 Thus, the
detection of prostate cancer in its potentially curable stages requires the use of
relatively low PSA cutoffs (4 ng/mL [4
ng/mL]), leading to unnecessary biopsies.
260
Increasing Test Specificity With
Determination of Percentage
Free PSA
PSA has been shown to exist in multiple forms in serum and is predominantly
bound to proteins, but one form of PSA
remains uncomplexed and is called free
PSA.9,10 Early studies demonstrated that
measurement of PSA forms in serum
could help discriminate between prostate
cancer and benign prostatic disease.11-18
For reasons yet unknown, men with
prostate cancer tend to have a lower percentage of free PSA (%FPSA = free
PSA/total PSA) than men with benign
disease.11-18
Therefore, these early research reports suggested that measurement of
%FPSA could increase the specificity of
PSA and decrease the number of unnecessary negative biopsy results. However,
the %FPSA literature has produced conflicting findings on recommended cutoffs,
specificity, and cancer probabilities,
which has led to confusion in the medical
community about how to use this marker.
Woodrum and colleagues19 summarized
the literature and listed the factors that
affect study results and produce inconsistent recommendations. These authors
showed that selection of the patient population (inclusion and exclusion criteria)
and use of different assay systems can
produce very different study outcomes.
Although many studies in the literature have not controlled for influencing
factors, there is consensus that %FPSA
increases the specificity of PSA for cancer
detection. However, since the guidelines
for use of the test have been inconsistent, a
large definitive study was conducted20 that
controlled for these factors, with use of
adequate sample size and a patient population in whom %FPSA testing would be
expected in clinical practice. This study
represents the largest series to date evaluating the use of %FPSA for both diagnosis
and staging in men with moderately elevated PSA levels, consisting of 773 men
with histologically confirmed diagnoses
(379 prostate cancer, 394 benign prostatic
disease). Of the 379 cancer patients, 268
(71%) underwent radical prostatectomy.20
This prospective multicenter trial
was conducted in men with moderately
elevated PSA levels (4-10 ng/mL [4-10
ng/mL)20 and was used to develop clinical guidelines and determine the appropriate cutoffs for the use of %FPSA. This
trial became the basis of the first free
PSA test approved by the FDA.
This study demonstrated that
%FPSA may be used in 2 ways: (1) as a
laboratorymedicine> may 2001> number 5> volume 32
©
single cutoff approach (for all patients),
or (2) for individual patient risk assessment (biopsy decisions based on each
individual patient’s risk of cancer).
Use of a Single Cutoff
The multicenter trial results showed
that using a cutoff of 25% or less FPSA
(ie, men with values at or below the cutoff undergo biopsy) would detect 95% of
cancers and spare 20% of men with benign disease from biopsy in men with a
total PSA concentration between 4.0 and
10.0 ng/mL (4.0 and 10.0 ng/mL) and a
palpably benign prostate gland.20
Receiver operating characteristic (ROC)
curves for total PSA and %FPSA are
shown in [F1]. A single cutoff of 25%
FPSA worked well regardless of age,
prostate size, or PSA level within the 4.0
to 10.0 ng/mL [4.0-10.0 ng/mL] range.
The 25% cutoff detected 98% of
cancers for men in their 50s, 94% for
men in their 60s, and 90% for men in
their early 70s. The cancers above the
cutoff that would be missed were more
prevalent in older men (who are often not
affected by or treated for prostate cancer)
and were generally less aggressive in
tumor grade and volume. With annual
screening, it would be possible to monitor
patients and perform biopsies only in patients with increasing PSA levels or decreasing %FPSA values to detect these
tumors that tend to be less advanced.
With the widespread use of PSA
screening, improvements in specificity
are desirable. Because most men with
PSA values between 4 and 10 ng/mL
(4.0-10.0 ng/mL) have benign disease,
sparing 20% from biopsy represents a
substantial number of men who would
not be required to undergo an unnecessary procedure. The cost-benefit equation
of prostate cancer detection programs is
most sensitive to changes in test specificity, such that minor increases in specificity (approximately 5%) produce
marked reductions (approximately 50%)
in net cost per individual screened.21
Important benefits, in addition to cost
considerations, include sparing men who
do not need biopsy from the discomfort
and anxiety of the procedure, as well as
possible complications such as infection,
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T1
Probability of Cancer, Based on PSA6,8 and %FPSA Results,20 for Men
With Normal Digital Rectal Examination Results*
PSA (ng/mL [ng/mL])
Probability of
Cancer (%)
0-2
~1
2.1-4
15
4.1-10
25
>10
>50
%FPSA
Probability of Cancer (%)
0-10
56
10-15
28
15-20
20
20-25
16
>25
8
PSA, prostate-specific antigen; %FPSA, percentage free prostate-specific antigen.
*%FPSA can further stratify risk for men with PSA values between 4 and 10 ng/mL (4 and 10 ng/mL).
fever, rectal bleeding, hematuria,
hematospermia, urinary retention, and
hospitalization in some cases.
Individual Patient Risk Assessment
The multicenter trial results also
showed that %FPSA may be used to determine the relative risk of cancer in individual men, with lower %FPSA values
indicating higher risk.20 [T1] shows that
the probability of cancer ranged from 8%
(men with %FPSA values > 25%) to 56%
(men with %FPSA values of 10% or less).
Thus, %FPSA may be used to group
individual men into low- to high-risk
populations to aid in biopsy decisions.
Family and patient history could be used
in combination with %FPSA results to
determine the preferred patient management plan for individual patients. Biopsy
may be recommended for a younger man
with a low ratio (high risk), but not be
recommended for an older man with a
high ratio (low risk).
In addition, patients who have undergone one biopsy with negative findings
might be advised to undergo a second
biopsy if the %FPSA value indicates high
risk; approximately 20% of cancers are
missed on the first biopsy.8 Thus, %FPSA
may detect cancers in high-risk populations that otherwise might be missed and
aid in determining which patients may
benefit most from a repeated biopsy.
%FPSA and Staging of
Prostate Cancer
In addition to determining appropriate guidelines for use of %FPSA in
prostate cancer detection, the multicenter
trial20 also evaluated whether %FPSA
could be useful in the staging of prostate
cancer and whether %FPSA could be
added to biopsy findings and other clinical information to more accurately predict postoperative outcome. The results
showed that preoperative serum %FPSA
values can be used to assist in the prediction of pathologic outcome of prostate
cancer patients with moderately elevated
PSA levels. Higher %FPSA values were
associated with less aggressive disease.
A value of 15% FPSA was found to provide the greatest discrimination in predicting favorable prognosis: 75% of
patients with more than 15% FPSA had
organ-confined cancer, favorable tumor
grade, and small tumors, whereas only
34% of patients with lower %FPSA values had these combined favorable features.20,22 However, this 15% FPSA
value should not be used as an absolute
cutoff point to determine appropriate
therapy. Rather, %FPSA may be combined with PSA, DRE, and biopsy findings to more accurately predict probable
postoperative pathologic stage and grade.
This information may then assist the patient and physician in making more informed treatment decisions.
These results verified earlier studies
in smaller cohorts of men suggesting
that %FPSA may be associated with
tumor pathology.16,23-26 Carter et al27
reported that %FPSA may be the
earliest marker of tumor behavior,
predicting aggressive cancer 10 years
before diagnosis, whereas total PSA
predicted aggressive cancer 5 years before diagnosis.
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laboratorymedicine> may 2001> number 5> volume 32
Other studies on the subject have not
observed a relationship to tumor pathology,28-30 but these studies generally consisted of patients with a wide range of
PSA values or used different assay systems. As seen with the use of free PSA
testing to distinguish between cancer and
benign hyperplasia, %FPSA appears to be
most effective in staging prostate cancer
when PSA levels are moderately elevated
(4-10 ng/mL [4.0-10.0 ng/mL]), since it is
difficult for a new marker to improve on
the considerable predictive value of total
PSA in patients with very low (<2 ng/mL
[<2 ng/mL]) or very high PSA (>20
ng/mL [>20 ng/mL]) concentrations.
PSA Velocity and Age-Specific
PSA Reference Ranges
Other methods have been proposed
to increase PSA specificity, including
age-specific PSA reference ranges31 and
PSA velocity (PSAV). PSAV is difficult
to put into practice because at least 3
serum samples over a 1- to 2-year period
are required.32 Biologic variation may
confound results, and PSAV is prone to
misinterpretation if serial samples from
the same patient are tested over time with
different manufacturers’ assays; assay-toassay variation may be greater than the
change in PSA values over time.33
The multicenter trial conducted to
assess the clinical performance of %FPSA
also compared this new marker to agespecific PSA reference ranges.20,34 Study
results demonstrated that both %FPSA and
age-specific PSA cutoffs enhanced the
specificity of total PSA for cancer detection in men with PSA values between 4
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and 10 ng/mL, but %FPSA maintained
significantly higher sensitivities than agespecific PSA cutoffs in men over 60 years
of age. Use of the recommended PSA cutoffs31 of 3.5 ng/mL (3.5 ng/mL), 4.5
ng/mL (4.5 ng/mL), and 6.5 ng/mL (6.5
ng/mL) in men aged 50 to 59, 60 to 69,
and 70 to 79, respectively, would have
missed nearly 20% of cancers in men in
their 60s and nearly 60% of cancers in
men in their 70s. In contrast, %FPSA
(25% cutoff) missed only 6% and 10%,
respectively, in these groups.34 As noted
previously, cancers missed by %FPSA
were more prevalent in older men (who
are often not affected by or treated for
prostate cancer) and were generally less
aggressive in tumor grade and volume.20,22
The clinical guidelines and cutoffs
discussed in this article were obtained
using Beckman Coulter’s M total and free
PSA assays, available on the Access immunoassay analyzer. The Access Hybritech
free PSA assay precision ranges from
2.16% to 3.36% for free PSA values ranging from 0.29 ng/mL (0.29 ng/mL) to
12.87 ng/mL (12.87 ng/mL), respectively.
Analytic sensitivity is less than 0.005
ng/mL (0.005 ng/mL). Studies in the literature have reported that %FPSA cutoffs and
clinical performance differ when various
combinations of free and total PSA assays
from different manufacturers are used.33,3537 Free and total PSA assays should be
from the same manufacturer to ensure accurate %FPSA results. Mean %FPSA values from identical serum samples may be
2-fold higher using different assay combinations.36 This is due to differences in
assay calibration, antibody specificity,
and/or nonequimolarity of the total PSA
assay used. Thus, the cutoffs presented
apply only to these assays; results from
other manufacturers’ assays may vary.
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1. Greenlee RT, Murray T, Bolden S, et al. Cancer
statistics, 2000. CA Cancer J Clin. 2000;50:7-33.
2. Ries LAG, Wingo PA, Miller DS, et al. The
annual report to the nation on the status of cancer,
1973-1997, with a special section on colorectal
cancer. Cancer. 2000;88:2398-2424.
3. Catalona WJ, Smith DS, Ratliff TL, et al.
Detection of organ-confined prostate cancer is
increased through prostate-specific antigen–based
screening. JAMA. 1993;270:948-954.
19. Woodrum DL, Brawer MK, Partin AW, et al.
Interpretation of free prostate specific antigen
clinical research studies for the detection of
prostate cancer. J Urol. 1997;159:5-12.
4. Ito K, Kubota Y, Suzuki K, et al. Correlation of
prostate-specific antigen before prostate cancer
detection and clinicopathologic features:
evaluation of mass screening populations.
Urology. 2000;55:705-709.
20. Catalona WJ, Partin AW, Slawin KM, et al. Use of
the percentage of free prostate specific antigen to
enhance differentiation of prostate cancer from
benign prostatic disease: a prospective multicenter
clinical trial. JAMA. 1998;279:1542-1547.
5. O’Dowd GJ, Veltri RW, Orozco R, et al. Update on
the appropriate staging evaluation for newly
diagnosed prostate cancer. J Urol. 1997;158:687-698.
6. Catalona WJ, Richie JP, Ahmann FR, et al.
Comparison of digital rectal examination and
serum prostate specific antigen in the early
detection of prostate cancer: results of a
multicenter clinical trial of 6,630 men. J Urol.
1994;151:1283-1290.
21. Littrup PJ, Goodman AC. Economic
considerations of prostate cancer: the role of
detection specificity and biopsy reduction.
Cancer. 1995;75(suppl):1987-1993.
22. Southwick PC, Catalona WJ, Partin AW, et al.
Prediction of post-radical prostatectomy
pathological outcome for stage T1c prostate
cancer with percent free prostate specific
antigen: a prospective multicenter clinical trial.
J Urol. 1999;162:1346-1351.
7. Smith DS, Catalona WJ, Herschman JD.
Longitudinal screening for prostate cancer with
prostate-specific antigen. JAMA. 1996;276:13091315.
8. Keetch DW, Catalona WJ, Smith DS. Serial
prostatic biopsies in men with persistently
elevated serum prostate specific antigen values. J
Urol. 1994;151:1571-1574.
23. Arcangeli CG, Shepherd DL, Smith DS, et al.
Correlation of percent free PSA and pathologic
features of prostatic carcinomas. J Urol.
1996;155(suppl):415.
9. Christensson A, Laurell CB, Lilja H. Enzymatic
activity of prostate-specific antigen and its
reactions with extracellular serine proteinase
inhibitors. Eur J Biochem. 1990;194:755-763.
24. Epstein JI, Chan DW, Sokoll LJ, et al.
Nonpalpable stage T1c prostate cancer: prediction
of insignificant disease using free/total prostatespecific antigen levels and needle biopsy findings.
J Urol. 1998;160:2407-2411.
10. Lilja H, Christensson A, Dahlen U, et al. Prostatespecific antigen in human serum occurs
predominantly in complex with alpha1antichymotrypsin. Clin Chem. 1991;37:1618-1625.
25. Arcangeli CG, Humphrey PA, Smith DS, et al.
Percentage of free serum prostate-specific antigen
as a predictor of pathological features of prostate
cancer in a screening population. Urology.
1998;51:558-565.
11. Stenman UH, Leinonen J, Alfthan H, et al. A
complex between prostate-specific antigen and
alpha-1-antichymotrypsin is the major form of
prostate-specific antigen in serum of patients with
prostatic cancer: assay of the complex improves
clinical sensitivity for cancer. Cancer Res.
1991;51:222-226.
26. Pannek J, Rittenhouse HG, Chan DW, et al. The
use of percent free prostate specific antigen for
staging clinically localized prostate cancer. J Urol.
1998;159:1238-1242.
12. Christensson A, Bjork T, Nilsson O, et al. Serum
prostate specific antigen complexed to alpha-1antichymotrypsin as an indicator of prostate
cancer. J Urol. 1993;150:100-105.
27. Carter HB, Partin AW, Luderer AA, et al.
Percentage of free prostate-specific antigen in sera
predicts aggressiveness of prostate cancer a
decade before diagnosis. Urology. 1997;49:379384.
13. Catalona WJ, Smith DS, Wolfert RL, et al.
Evaluation of percentage of free serum prostatespecific antigen to improve specificity of prostate
cancer screening. JAMA. 1995;274:1214-1220.
28. Pannek J, Subong ENP, Jones K, et al. The role of
free/total prostate-specific antigen ratio in the
prediction of final pathologic stage for men with
clinically localized prostate cancer. Urology.
1996;48(suppl):51-54.
14. Partin AW, Catalona WJ, Southwick PC, et al.
Analysis of percent free prostate-specific antigen
(PSA) for prostate cancer detection: influence of
total PSA, prostate volume, and age. Urology.
1996;48(suppl):55-61.
29. Lerner SE, Jacobsen SJ, Lilja H, et al. Free,
complexed, and total serum prostate-specific
antigen concentrations and their proportions in
predicting stage, grade, and deoxyribonucleic acid
ploidy in patients with adenocarcinoma of the
prostate. Urology. 1996;48:240-248.
15. Luderer AA, Chen Y, Soriano TF, et al.
Measurement of the proportion of free to total
prostate-specific antigen improves diagnostic
performance of prostate-specific antigen in the
diagnostic gray zone of total prostate-specific
antigen. Urology. 1995;46:187-194.
30. Bangma CH, Kranse R, Blijenberg BG, et al. The
free-to-total serum prostate specific antigen ratio
for staging prostate carcinoma. J Urol.
1997;157:544-547.
16. Elgamal AA, Cornillie FJ, Van Poppel HP, et al.
Free-to-total prostate specific antigen ratio as a
single test for detection of significant stage T1c
prostate cancer. J Urol. 1996;156:1042-1049.
31. Oesterling JE, Jacobsen SJ, Chute CG, et al.
Serum prostate-specific antigen in a communitybased population of healthy men: establishment of
age-specific reference ranges. JAMA.
1993;270:860-864.
17. Van Cangh PJ, De Nayer P, Sauvage P, et al. Free
to total prostate-specific antigen (PSA) ratio is
superior to total PSA in differentiating benign
prostate hypertrophy from prostate cancer.
Prostate. 1996;7(suppl):30-34.
32. Smith DS, Catalona WJ. Rate of change in serum
prostate specific antigen levels as a method for
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18. Chen YT, Luderer AA, Thiel RP, et al. Using
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33. Semjonow A, Brandt B, Oberpenning F, et al.
Discordance of assay methods creates pitfalls for
the interpretation of prostate-specific antigen
values. Prostate. 1996;7(suppl):3-16.
©
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34. Catalona WJ, Southwick PC, Slawin KM, et al.
Comparison of percent free PSA, PSA density,
and age-specific PSA cutoffs for prostate cancer
detection and staging. Urology. 2000;57:255-260.
36. Fortunato A, Dorizzi RM, Marchi G, et al.
fPSA/tPSA ratios obtained using nine
commercial assays. Clin Chem.
1996;42(suppl):268.
35. Chan DW, Sokoll LJ, Jones KA, et al. Clinical
evaluation of two free PSA assays in
combination with different total PSA assays. J
Urol. 1997;157(suppl):112.
37. Jung K, Stephan C, Lein M, et al. Analytical
performance and clinical validity of two free
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InterNetConnect
American Cancer Society
<www.cancer.org>
American Urological Association
<www.auanet.org>
US TOO!
<www.ustoo.com>
Beckman Coulter M
(prostate cancer information)
<www.beckmancoulter.com/
beckman/clindiag/prodinfo/prostate>
instrumentation [management/administration and training | generalist]
Ergonomics in the Laboratory
Terry Jo Gile, MT(ASCP)MA Ed
From Gile and Associates, St Louis, MO
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Musculoskeletal disorders such as
carpal tunnel syndrome and lower back
pain constitute the most important cause
of work-related absence due to illness and
occupational disability. These conditions
can be attributed in part to poor design of
equipment, technical systems, and tasks.
The reporting of musculoskeletal disorders and other work-related disorders attributable to ergonomic hazards has
increased significantly in the laboratory.
Transcriptionists, phlebotomists, and histotechnologists are most prone to musculoskeletal disorders due to the repetitive
nature of their work.
do not associate their pain with work because symptoms may occur only during
nonwork hours.
According to the National Safety
Council, back disorders account for
31% of all musculoskeletal disorders
and are frequently caused by faulty
body mechanics such as poor posture;
bending and reaching; and carrying,
moving, or lifting loads that are too
heavy or too big.1
Keeping the body in a neutral position with the work close to the body is
helpful in maintaining proper posture.
Additionally, distributing rest time
throughout the day can reduce muscle
fatigue. For example, the musculoskeletal
system benefits more from a 5-minute
break every hour than it does from a 15minute break every 4 hours.
Ergonomic Disorders
Although there are a variety of ergonomic disorders, the most common are
carpal tunnel syndrome and back disorders. Carpal tunnel syndrome causes tingling, numbness, or severe pain in the
wrist and hand as well as reduced
strength in the hand. If the pressure on
the median nerve of the hand persists, it
can cause permanent loss of sensation
and even partial paralysis. People often
Work-Site Analysis
The first step in evaluating an ergonomic disorder is a work-site analysis
to determine what jobs and workstations
are the sources of the greatest problems.
Each workstation that is considered a
problem or high risk should be analyzed
by direct observation with assistance
from qualified personnel such as an ergonomist, a health-care provider, or an
affected employee. Use of a symptom
Ergonomic disorders
Work-site analysis
Workplace design
Administrative controls
©
laboratorymedicine> may 2001> number 5> volume 32
On March 6, 2001, marking the first
time the Congressional Review Act had
been used to repeal a federal regulation,
Senate Resolution 6 to rescind the
Occupational Safety and Health
Administration (OSHA) Ergonomic
Standard was passed, and on March 7,
2001, House Resolution 79 to rescind
OSHA’s Ergonomic Standard was also
passed. President Bush signed these
resolutions into law on Tuesday, March
20, 2001. OSHA’s Ergonomic Standard
was issued shortly before former
President Clinton left office; the list of
regulations that formed the standard
were aimed at preventing carpal tunnel
syndrome, tendinitis, and other kinds of
repetitive stress disorders.
Although some insiders believe
that in rescinding the standard,
Congress is stopping OSHA from
protecting Americans against repetitive
stress disorders, others believe that the
newly appointed Secretary of Labor,
Elaine Chao, will instead take this
opportunity to revamp the Ergonomic
Standard. The process of revamping
the standard could include revisiting
some research that may be outdated
and clarifying the impact of the
standard on small business through an
economic impact statement.
263
Thyroid Goiter, Nodules, and
Thyroid Cancer
Enlargement of the thyroid gland
(goiter), which is common, can be diffuse
or consist of 1 or more nodules. Because
any type of thyroid enlargement can be
associated with normal or altered thyroid
function, a patient with an abnormal thyroid gland should first undergo TSH level
assessment. Patients with hypothyroidism
or hyperthyroidism undergo testing and
are treated as outlined in the previous section. Euthyroid patients with goiters are
usually observed without treatment unless
the goiter itself is causing symptoms.
Euthyroid patients with single, large, or
suspicious nodules should undergo fineneedle aspiration biopsy of the nodule to
rule out cancer. In the past, many benign
goiters and thyroid nodules were treated
with L-T4 suppression therapy, but studies have shown that this is not especially
effective and leads to possible long-term
adverse effects on the heart and bone.
Approximately 5% of thyroid nodules are shown to contain thyroid cancer
at surgery.10 Most cases of thyroid cancer
are best treated with a combination of
surgery, radioactive iodine, and L-T4 therapy. In this case, L-T4 is administered at
doses that suppress TSH to low levels,
since TSH acts a growth factor for thyroid cancer. Patients are observed with
assessment of thyroid hormone levels and
Tg levels and the use of radioactive iodine whole-body scans to detect residual
or recurrent disease.10
1. Schussler GC. The thyroxine-binding proteins.
Thyroid. 2000;10:141-147.
2. Nelson JC, Wilcox RB. Analytic performance of
free and total thyroxine assays. Clin Chem.
1996;42:146-154.
4. Franklyn JA, Black EG, Betteridge J, et al.
Comparison of second and third generation TSH
assays in NTI, hyperthyroidism and in L-thyroxine
treated patients. J Clin Endocrinol Metab.
1994;78:1368-1371.
5. Spencer CA, Wang CC. Thyroglobulin
measurement: techniques, benefits, and pitfalls.
Endocrinol Metab Clin North Am. 1995;24:841849.
6. Burman KD, Pandian R. Clinical utility of assays
for TSH receptor antibodies. Endocrinologist.
1998;8:284-290.
7. Dayan CM, Daniels GH. Chronic autoimmune
thyroiditis. N Engl J Med. 1996;335:99-107.
8. Samuels MH. Subclinical thyroid disease in the
elderly. Thyroid. 1998;8:803-813.
9. Weetman AP. Medical progress: Graves disease. N
Engl J Med. 2000;343:1236-1248.
10. Schlumberger MJ. Papillary and follicular thyroid
carcinoma. N Engl J Med. 1998;338:297-306.
InterNetConnect
American Thyroid Association
<www.thyroid.org>
3. Klee GG. Clinical usage recommendations and
analytic performance goals for total and free
triiodothyronine measurements. Clin Chem.
1996;42:155-159.
interpretation [chemistry]
The Role of Free PSA in the Detection
of Prostate Cancer
Paula C. Southwick, PhD, CCRA, RAC
From the Department of Research and Development, Beckman Coulter, Fullerton, CA
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Increasing test specificity with
determination of percentage of free
prostate-specific antigen (%FPSA)
%FPSA for single cutoff approach
and individual patient risk assessment
%FPSA and staging of prostate
cancer
Comparison of %FPSA to PSA
velocity and age-specific PSA
reference ranges
Detection of Prostate Cancer
With Prostate-Specific Antigen
Prostate cancer is the most common
type of cancer found in men in the
United States, and it is the second leading cause of cancer deaths among
men.1,2 One in 10 men will be diagnosed
with prostate cancer in his lifetime, and
one third will die of the disease.1,2
Historically, the only methods available for the detection of prostate cancer
were digital rectal examination (DRE) and
prostatic acid phosphatase measurement.
Unfortunately, most prostate cancers detected with these methods were at an advanced stage at the time of diagnosis.3-5
In the early 1990s, measurement of
prostate-specific antigen (PSA) in serum
was evaluated for use in the detection of
prostate cancer. PSA, a serine protease, is
produced by both benign and malignant
cells of the prostate. Abnormalities in the
prostate gland architecture resulting from
disease can lead to leakage of PSA into
the bloodstream.
In a large, prospective multicenter clinical trial, PSA and DRE were compared for
effectiveness in prostate cancer detection in
nearly 7,000 men.6 PSA was found to detect more cancers than DRE (82% vs 55%,
©
laboratorymedicine> may 2001> number 5> volume 32
respectively); the highest rates of cancer
detection were obtained by using the 2 tests
together. This trial became the basis of the
first PSA test approved by the US Food and
Drug Administration (FDA) for prostate
cancer detection.
PSA testing over time has also contributed to a shift in detection of earlierstage disease, from the historically
observed 70% advanced cancer at diagnosis to the currently observed 30%
advanced cancer.3,7 The National Cancer
Institute recently announced that the
prostate cancer death rate in the United
States declined throughout the 1990s,
providing the first evidence that early detection may decrease mortality rates.
Limitations of PSA Testing
Although PSA is now widely used for
prostate cancer detection, a limitation has
259
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[F1] Receiver operating characteristic curves for
total prostate-specific antigen (PSA) and
percentage of free PSA (%FPSA). The area under
the curve (AUC) is significantly greater for %FPSA
than for total PSA in men with moderately
elevated PSA concentrations (4-10 ng/mL [4.010.0 ng/mL]). A cutoff of 25% FPSA yields 95%
sensitivity and enhances the specificity of PSA for
prostate cancer screening by sparing 20% of men
with benign disease from unnecessary biopsy.
been its relative lack of specificity when
serum concentrations are moderately elevated (4.0-10.0 ng/mL [4.0-10.0 ng/mL]).
In this range, PSA identifies men as high
risk (25% will have prostate cancer, compared with 4% in the general population of
men over 50 years of age6,8), but specificity
could be improved because within this
PSA range, 75% of biopsy results are negative and unnecessary.
Most patients with prostate cancer
and PSA in this range have early-stage
disease, whereas more than half of the
men with PSA levels above 10 ng/mL (10
ng/mL) have advanced disease.6 Thus, the
detection of prostate cancer in its potentially curable stages requires the use of
relatively low PSA cutoffs (4 ng/mL [4
ng/mL]), leading to unnecessary biopsies.
260
Increasing Test Specificity With
Determination of Percentage
Free PSA
PSA has been shown to exist in multiple forms in serum and is predominantly
bound to proteins, but one form of PSA
remains uncomplexed and is called free
PSA.9,10 Early studies demonstrated that
measurement of PSA forms in serum
could help discriminate between prostate
cancer and benign prostatic disease.11-18
For reasons yet unknown, men with
prostate cancer tend to have a lower percentage of free PSA (%FPSA = free
PSA/total PSA) than men with benign
disease.11-18
Therefore, these early research reports suggested that measurement of
%FPSA could increase the specificity of
PSA and decrease the number of unnecessary negative biopsy results. However,
the %FPSA literature has produced conflicting findings on recommended cutoffs,
specificity, and cancer probabilities,
which has led to confusion in the medical
community about how to use this marker.
Woodrum and colleagues19 summarized
the literature and listed the factors that
affect study results and produce inconsistent recommendations. These authors
showed that selection of the patient population (inclusion and exclusion criteria)
and use of different assay systems can
produce very different study outcomes.
Although many studies in the literature have not controlled for influencing
factors, there is consensus that %FPSA
increases the specificity of PSA for cancer
detection. However, since the guidelines
for use of the test have been inconsistent, a
large definitive study was conducted20 that
controlled for these factors, with use of
adequate sample size and a patient population in whom %FPSA testing would be
expected in clinical practice. This study
represents the largest series to date evaluating the use of %FPSA for both diagnosis
and staging in men with moderately elevated PSA levels, consisting of 773 men
with histologically confirmed diagnoses
(379 prostate cancer, 394 benign prostatic
disease). Of the 379 cancer patients, 268
(71%) underwent radical prostatectomy.20
This prospective multicenter trial
was conducted in men with moderately
elevated PSA levels (4-10 ng/mL [4-10
ng/mL)20 and was used to develop clinical guidelines and determine the appropriate cutoffs for the use of %FPSA. This
trial became the basis of the first free
PSA test approved by the FDA.
This study demonstrated that
%FPSA may be used in 2 ways: (1) as a
laboratorymedicine> may 2001> number 5> volume 32
©
single cutoff approach (for all patients),
or (2) for individual patient risk assessment (biopsy decisions based on each
individual patient’s risk of cancer).
Use of a Single Cutoff
The multicenter trial results showed
that using a cutoff of 25% or less FPSA
(ie, men with values at or below the cutoff undergo biopsy) would detect 95% of
cancers and spare 20% of men with benign disease from biopsy in men with a
total PSA concentration between 4.0 and
10.0 ng/mL (4.0 and 10.0 ng/mL) and a
palpably benign prostate gland.20
Receiver operating characteristic (ROC)
curves for total PSA and %FPSA are
shown in [F1]. A single cutoff of 25%
FPSA worked well regardless of age,
prostate size, or PSA level within the 4.0
to 10.0 ng/mL [4.0-10.0 ng/mL] range.
The 25% cutoff detected 98% of
cancers for men in their 50s, 94% for
men in their 60s, and 90% for men in
their early 70s. The cancers above the
cutoff that would be missed were more
prevalent in older men (who are often not
affected by or treated for prostate cancer)
and were generally less aggressive in
tumor grade and volume. With annual
screening, it would be possible to monitor
patients and perform biopsies only in patients with increasing PSA levels or decreasing %FPSA values to detect these
tumors that tend to be less advanced.
With the widespread use of PSA
screening, improvements in specificity
are desirable. Because most men with
PSA values between 4 and 10 ng/mL
(4.0-10.0 ng/mL) have benign disease,
sparing 20% from biopsy represents a
substantial number of men who would
not be required to undergo an unnecessary procedure. The cost-benefit equation
of prostate cancer detection programs is
most sensitive to changes in test specificity, such that minor increases in specificity (approximately 5%) produce
marked reductions (approximately 50%)
in net cost per individual screened.21
Important benefits, in addition to cost
considerations, include sparing men who
do not need biopsy from the discomfort
and anxiety of the procedure, as well as
possible complications such as infection,
왗your lab focus 왘
T1
Probability of Cancer, Based on PSA6,8 and %FPSA Results,20 for Men
With Normal Digital Rectal Examination Results*
PSA (ng/mL [ng/mL])
Probability of
Cancer (%)
0-2
~1
2.1-4
15
4.1-10
25
>10
>50
%FPSA
Probability of Cancer (%)
0-10
56
10-15
28
15-20
20
20-25
16
>25
8
PSA, prostate-specific antigen; %FPSA, percentage free prostate-specific antigen.
*%FPSA can further stratify risk for men with PSA values between 4 and 10 ng/mL (4 and 10 ng/mL).
fever, rectal bleeding, hematuria,
hematospermia, urinary retention, and
hospitalization in some cases.
Individual Patient Risk Assessment
The multicenter trial results also
showed that %FPSA may be used to determine the relative risk of cancer in individual men, with lower %FPSA values
indicating higher risk.20 [T1] shows that
the probability of cancer ranged from 8%
(men with %FPSA values > 25%) to 56%
(men with %FPSA values of 10% or less).
Thus, %FPSA may be used to group
individual men into low- to high-risk
populations to aid in biopsy decisions.
Family and patient history could be used
in combination with %FPSA results to
determine the preferred patient management plan for individual patients. Biopsy
may be recommended for a younger man
with a low ratio (high risk), but not be
recommended for an older man with a
high ratio (low risk).
In addition, patients who have undergone one biopsy with negative findings
might be advised to undergo a second
biopsy if the %FPSA value indicates high
risk; approximately 20% of cancers are
missed on the first biopsy.8 Thus, %FPSA
may detect cancers in high-risk populations that otherwise might be missed and
aid in determining which patients may
benefit most from a repeated biopsy.
%FPSA and Staging of
Prostate Cancer
In addition to determining appropriate guidelines for use of %FPSA in
prostate cancer detection, the multicenter
trial20 also evaluated whether %FPSA
could be useful in the staging of prostate
cancer and whether %FPSA could be
added to biopsy findings and other clinical information to more accurately predict postoperative outcome. The results
showed that preoperative serum %FPSA
values can be used to assist in the prediction of pathologic outcome of prostate
cancer patients with moderately elevated
PSA levels. Higher %FPSA values were
associated with less aggressive disease.
A value of 15% FPSA was found to provide the greatest discrimination in predicting favorable prognosis: 75% of
patients with more than 15% FPSA had
organ-confined cancer, favorable tumor
grade, and small tumors, whereas only
34% of patients with lower %FPSA values had these combined favorable features.20,22 However, this 15% FPSA
value should not be used as an absolute
cutoff point to determine appropriate
therapy. Rather, %FPSA may be combined with PSA, DRE, and biopsy findings to more accurately predict probable
postoperative pathologic stage and grade.
This information may then assist the patient and physician in making more informed treatment decisions.
These results verified earlier studies
in smaller cohorts of men suggesting
that %FPSA may be associated with
tumor pathology.16,23-26 Carter et al27
reported that %FPSA may be the
earliest marker of tumor behavior,
predicting aggressive cancer 10 years
before diagnosis, whereas total PSA
predicted aggressive cancer 5 years before diagnosis.
©
laboratorymedicine> may 2001> number 5> volume 32
Other studies on the subject have not
observed a relationship to tumor pathology,28-30 but these studies generally consisted of patients with a wide range of
PSA values or used different assay systems. As seen with the use of free PSA
testing to distinguish between cancer and
benign hyperplasia, %FPSA appears to be
most effective in staging prostate cancer
when PSA levels are moderately elevated
(4-10 ng/mL [4.0-10.0 ng/mL]), since it is
difficult for a new marker to improve on
the considerable predictive value of total
PSA in patients with very low (<2 ng/mL
[<2 ng/mL]) or very high PSA (>20
ng/mL [>20 ng/mL]) concentrations.
PSA Velocity and Age-Specific
PSA Reference Ranges
Other methods have been proposed
to increase PSA specificity, including
age-specific PSA reference ranges31 and
PSA velocity (PSAV). PSAV is difficult
to put into practice because at least 3
serum samples over a 1- to 2-year period
are required.32 Biologic variation may
confound results, and PSAV is prone to
misinterpretation if serial samples from
the same patient are tested over time with
different manufacturers’ assays; assay-toassay variation may be greater than the
change in PSA values over time.33
The multicenter trial conducted to
assess the clinical performance of %FPSA
also compared this new marker to agespecific PSA reference ranges.20,34 Study
results demonstrated that both %FPSA and
age-specific PSA cutoffs enhanced the
specificity of total PSA for cancer detection in men with PSA values between 4
261
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and 10 ng/mL, but %FPSA maintained
significantly higher sensitivities than agespecific PSA cutoffs in men over 60 years
of age. Use of the recommended PSA cutoffs31 of 3.5 ng/mL (3.5 ng/mL), 4.5
ng/mL (4.5 ng/mL), and 6.5 ng/mL (6.5
ng/mL) in men aged 50 to 59, 60 to 69,
and 70 to 79, respectively, would have
missed nearly 20% of cancers in men in
their 60s and nearly 60% of cancers in
men in their 70s. In contrast, %FPSA
(25% cutoff) missed only 6% and 10%,
respectively, in these groups.34 As noted
previously, cancers missed by %FPSA
were more prevalent in older men (who
are often not affected by or treated for
prostate cancer) and were generally less
aggressive in tumor grade and volume.20,22
The clinical guidelines and cutoffs
discussed in this article were obtained
using Beckman Coulter’s M total and free
PSA assays, available on the Access immunoassay analyzer. The Access Hybritech
free PSA assay precision ranges from
2.16% to 3.36% for free PSA values ranging from 0.29 ng/mL (0.29 ng/mL) to
12.87 ng/mL (12.87 ng/mL), respectively.
Analytic sensitivity is less than 0.005
ng/mL (0.005 ng/mL). Studies in the literature have reported that %FPSA cutoffs and
clinical performance differ when various
combinations of free and total PSA assays
from different manufacturers are used.33,3537 Free and total PSA assays should be
from the same manufacturer to ensure accurate %FPSA results. Mean %FPSA values from identical serum samples may be
2-fold higher using different assay combinations.36 This is due to differences in
assay calibration, antibody specificity,
and/or nonequimolarity of the total PSA
assay used. Thus, the cutoffs presented
apply only to these assays; results from
other manufacturers’ assays may vary.
262
1. Greenlee RT, Murray T, Bolden S, et al. Cancer
statistics, 2000. CA Cancer J Clin. 2000;50:7-33.
2. Ries LAG, Wingo PA, Miller DS, et al. The
annual report to the nation on the status of cancer,
1973-1997, with a special section on colorectal
cancer. Cancer. 2000;88:2398-2424.
3. Catalona WJ, Smith DS, Ratliff TL, et al.
Detection of organ-confined prostate cancer is
increased through prostate-specific antigen–based
screening. JAMA. 1993;270:948-954.
19. Woodrum DL, Brawer MK, Partin AW, et al.
Interpretation of free prostate specific antigen
clinical research studies for the detection of
prostate cancer. J Urol. 1997;159:5-12.
4. Ito K, Kubota Y, Suzuki K, et al. Correlation of
prostate-specific antigen before prostate cancer
detection and clinicopathologic features:
evaluation of mass screening populations.
Urology. 2000;55:705-709.
20. Catalona WJ, Partin AW, Slawin KM, et al. Use of
the percentage of free prostate specific antigen to
enhance differentiation of prostate cancer from
benign prostatic disease: a prospective multicenter
clinical trial. JAMA. 1998;279:1542-1547.
5. O’Dowd GJ, Veltri RW, Orozco R, et al. Update on
the appropriate staging evaluation for newly
diagnosed prostate cancer. J Urol. 1997;158:687-698.
6. Catalona WJ, Richie JP, Ahmann FR, et al.
Comparison of digital rectal examination and
serum prostate specific antigen in the early
detection of prostate cancer: results of a
multicenter clinical trial of 6,630 men. J Urol.
1994;151:1283-1290.
21. Littrup PJ, Goodman AC. Economic
considerations of prostate cancer: the role of
detection specificity and biopsy reduction.
Cancer. 1995;75(suppl):1987-1993.
22. Southwick PC, Catalona WJ, Partin AW, et al.
Prediction of post-radical prostatectomy
pathological outcome for stage T1c prostate
cancer with percent free prostate specific
antigen: a prospective multicenter clinical trial.
J Urol. 1999;162:1346-1351.
7. Smith DS, Catalona WJ, Herschman JD.
Longitudinal screening for prostate cancer with
prostate-specific antigen. JAMA. 1996;276:13091315.
8. Keetch DW, Catalona WJ, Smith DS. Serial
prostatic biopsies in men with persistently
elevated serum prostate specific antigen values. J
Urol. 1994;151:1571-1574.
23. Arcangeli CG, Shepherd DL, Smith DS, et al.
Correlation of percent free PSA and pathologic
features of prostatic carcinomas. J Urol.
1996;155(suppl):415.
9. Christensson A, Laurell CB, Lilja H. Enzymatic
activity of prostate-specific antigen and its
reactions with extracellular serine proteinase
inhibitors. Eur J Biochem. 1990;194:755-763.
24. Epstein JI, Chan DW, Sokoll LJ, et al.
Nonpalpable stage T1c prostate cancer: prediction
of insignificant disease using free/total prostatespecific antigen levels and needle biopsy findings.
J Urol. 1998;160:2407-2411.
10. Lilja H, Christensson A, Dahlen U, et al. Prostatespecific antigen in human serum occurs
predominantly in complex with alpha1antichymotrypsin. Clin Chem. 1991;37:1618-1625.
25. Arcangeli CG, Humphrey PA, Smith DS, et al.
Percentage of free serum prostate-specific antigen
as a predictor of pathological features of prostate
cancer in a screening population. Urology.
1998;51:558-565.
11. Stenman UH, Leinonen J, Alfthan H, et al. A
complex between prostate-specific antigen and
alpha-1-antichymotrypsin is the major form of
prostate-specific antigen in serum of patients with
prostatic cancer: assay of the complex improves
clinical sensitivity for cancer. Cancer Res.
1991;51:222-226.
26. Pannek J, Rittenhouse HG, Chan DW, et al. The
use of percent free prostate specific antigen for
staging clinically localized prostate cancer. J Urol.
1998;159:1238-1242.
12. Christensson A, Bjork T, Nilsson O, et al. Serum
prostate specific antigen complexed to alpha-1antichymotrypsin as an indicator of prostate
cancer. J Urol. 1993;150:100-105.
27. Carter HB, Partin AW, Luderer AA, et al.
Percentage of free prostate-specific antigen in sera
predicts aggressiveness of prostate cancer a
decade before diagnosis. Urology. 1997;49:379384.
13. Catalona WJ, Smith DS, Wolfert RL, et al.
Evaluation of percentage of free serum prostatespecific antigen to improve specificity of prostate
cancer screening. JAMA. 1995;274:1214-1220.
28. Pannek J, Subong ENP, Jones K, et al. The role of
free/total prostate-specific antigen ratio in the
prediction of final pathologic stage for men with
clinically localized prostate cancer. Urology.
1996;48(suppl):51-54.
14. Partin AW, Catalona WJ, Southwick PC, et al.
Analysis of percent free prostate-specific antigen
(PSA) for prostate cancer detection: influence of
total PSA, prostate volume, and age. Urology.
1996;48(suppl):55-61.
29. Lerner SE, Jacobsen SJ, Lilja H, et al. Free,
complexed, and total serum prostate-specific
antigen concentrations and their proportions in
predicting stage, grade, and deoxyribonucleic acid
ploidy in patients with adenocarcinoma of the
prostate. Urology. 1996;48:240-248.
15. Luderer AA, Chen Y, Soriano TF, et al.
Measurement of the proportion of free to total
prostate-specific antigen improves diagnostic
performance of prostate-specific antigen in the
diagnostic gray zone of total prostate-specific
antigen. Urology. 1995;46:187-194.
30. Bangma CH, Kranse R, Blijenberg BG, et al. The
free-to-total serum prostate specific antigen ratio
for staging prostate carcinoma. J Urol.
1997;157:544-547.
16. Elgamal AA, Cornillie FJ, Van Poppel HP, et al.
Free-to-total prostate specific antigen ratio as a
single test for detection of significant stage T1c
prostate cancer. J Urol. 1996;156:1042-1049.
31. Oesterling JE, Jacobsen SJ, Chute CG, et al.
Serum prostate-specific antigen in a communitybased population of healthy men: establishment of
age-specific reference ranges. JAMA.
1993;270:860-864.
17. Van Cangh PJ, De Nayer P, Sauvage P, et al. Free
to total prostate-specific antigen (PSA) ratio is
superior to total PSA in differentiating benign
prostate hypertrophy from prostate cancer.
Prostate. 1996;7(suppl):30-34.
32. Smith DS, Catalona WJ. Rate of change in serum
prostate specific antigen levels as a method for
prostate cancer detection. J Urol. 1994:152:11631167.
18. Chen YT, Luderer AA, Thiel RP, et al. Using
proportions of free to total prostate-specific
antigen, age, and total prostate-specific antigen to
predict the probability of prostate cancer. Urology.
1996;47:518-524.
laboratorymedicine> may 2001> number 5> volume 32
33. Semjonow A, Brandt B, Oberpenning F, et al.
Discordance of assay methods creates pitfalls for
the interpretation of prostate-specific antigen
values. Prostate. 1996;7(suppl):3-16.
©
왗your lab focus 왘
34. Catalona WJ, Southwick PC, Slawin KM, et al.
Comparison of percent free PSA, PSA density,
and age-specific PSA cutoffs for prostate cancer
detection and staging. Urology. 2000;57:255-260.
36. Fortunato A, Dorizzi RM, Marchi G, et al.
fPSA/tPSA ratios obtained using nine
commercial assays. Clin Chem.
1996;42(suppl):268.
35. Chan DW, Sokoll LJ, Jones KA, et al. Clinical
evaluation of two free PSA assays in
combination with different total PSA assays. J
Urol. 1997;157(suppl):112.
37. Jung K, Stephan C, Lein M, et al. Analytical
performance and clinical validity of two free
prostate-specific antigen assays compared. Clin
Chem. 1996;42:1026-1033.
InterNetConnect
American Cancer Society
<www.cancer.org>
American Urological Association
<www.auanet.org>
US TOO!
<www.ustoo.com>
Beckman Coulter M
(prostate cancer information)
<www.beckmancoulter.com/
beckman/clindiag/prodinfo/prostate>
instrumentation [management/administration and training | generalist]
Ergonomics in the Laboratory
Terry Jo Gile, MT(ASCP)MA Ed
From Gile and Associates, St Louis, MO
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Musculoskeletal disorders such as
carpal tunnel syndrome and lower back
pain constitute the most important cause
of work-related absence due to illness and
occupational disability. These conditions
can be attributed in part to poor design of
equipment, technical systems, and tasks.
The reporting of musculoskeletal disorders and other work-related disorders attributable to ergonomic hazards has
increased significantly in the laboratory.
Transcriptionists, phlebotomists, and histotechnologists are most prone to musculoskeletal disorders due to the repetitive
nature of their work.
do not associate their pain with work because symptoms may occur only during
nonwork hours.
According to the National Safety
Council, back disorders account for
31% of all musculoskeletal disorders
and are frequently caused by faulty
body mechanics such as poor posture;
bending and reaching; and carrying,
moving, or lifting loads that are too
heavy or too big.1
Keeping the body in a neutral position with the work close to the body is
helpful in maintaining proper posture.
Additionally, distributing rest time
throughout the day can reduce muscle
fatigue. For example, the musculoskeletal
system benefits more from a 5-minute
break every hour than it does from a 15minute break every 4 hours.
Ergonomic Disorders
Although there are a variety of ergonomic disorders, the most common are
carpal tunnel syndrome and back disorders. Carpal tunnel syndrome causes tingling, numbness, or severe pain in the
wrist and hand as well as reduced
strength in the hand. If the pressure on
the median nerve of the hand persists, it
can cause permanent loss of sensation
and even partial paralysis. People often
Work-Site Analysis
The first step in evaluating an ergonomic disorder is a work-site analysis
to determine what jobs and workstations
are the sources of the greatest problems.
Each workstation that is considered a
problem or high risk should be analyzed
by direct observation with assistance
from qualified personnel such as an ergonomist, a health-care provider, or an
affected employee. Use of a symptom
Ergonomic disorders
Work-site analysis
Workplace design
Administrative controls
©
laboratorymedicine> may 2001> number 5> volume 32
On March 6, 2001, marking the first
time the Congressional Review Act had
been used to repeal a federal regulation,
Senate Resolution 6 to rescind the
Occupational Safety and Health
Administration (OSHA) Ergonomic
Standard was passed, and on March 7,
2001, House Resolution 79 to rescind
OSHA’s Ergonomic Standard was also
passed. President Bush signed these
resolutions into law on Tuesday, March
20, 2001. OSHA’s Ergonomic Standard
was issued shortly before former
President Clinton left office; the list of
regulations that formed the standard
were aimed at preventing carpal tunnel
syndrome, tendinitis, and other kinds of
repetitive stress disorders.
Although some insiders believe
that in rescinding the standard,
Congress is stopping OSHA from
protecting Americans against repetitive
stress disorders, others believe that the
newly appointed Secretary of Labor,
Elaine Chao, will instead take this
opportunity to revamp the Ergonomic
Standard. The process of revamping
the standard could include revisiting
some research that may be outdated
and clarifying the impact of the
standard on small business through an
economic impact statement.
263
