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Prostate-specific antigen complexed to alpha(1)-antichymotrypsin in the early detection of prostate cancer.

OBJECTIVES: To study the usefulness of the complexed-to-total (C:T) prostate-specific antigen (PSA) ratio in the early detection of prostate cancer in patients with a total PSA value <4.0 ng/ml. PATIENTS AND METHODS: Total PSA and PSA complexed to alpha(1)-antichymotrypsin were measured in plasma from 193 men with benign prostatic hyperplasia (BPH) and 34 with prostate cancer. The diagnosis was confirmed in 28 BPH and 16 prostate cancer patients by biopsy and in 165 BPH and 18 prostate cancer patients by histological study following transurethral prostatectomy or open prostatectomy. RESULTS: The area under the receiver operating characteristic (ROC) curve was significantly greater for the C:T PSA ratio (0.908) than for total PSA (0.692) (p<0.001). Using a cut-off point of 0.83 for the C:T PSA ratio and regardless of the digital rectal examination (DRE) finding, 20 of the 34 prostate cancer patients would have been given a correct diagnosis (59% sensitivity) and in only 8 of the 193 BPH patients would a biopsy have been necessary (96% specificity). With a cut-off of 0.79, the sensitivity increased to 85% with a specificity of 92%. When the analysis was restricted to the 44 patients with abnormal DRE, the area under the ROC curve for the C:T PSA ratio was 0.919, and a cut-off point of 0. 78 gave a sensitivity of 87% and a specificity of 93%. Using a cut-off of 0.63, all prostate cancers were detected (100% sensitivity) and 54% of the negative biopsies would have been eliminated. For the 183 patients diagnosed following surgery, a cut-off of 0.82 gave a sensitivity of 72% and a specificity of 94%. CONCLUSION: Our results show that the C:T PSA ratio significantly improves the clinical utility of the PSA assay for detecting prostate cancer in patients with total PSA < 4 ng/ml, increasing the sensitivity without significantly increasing the number of biopsies.

Aged↗

Relationship of prostate-specific antigen levels to prostate volume and age in mass screening subjects.

To evaluate the relationship between prostate-specific antigen (PSA) levels and prostate volume and age in a mass screening for prostatic disease, a total of 1,162 examinees from one Japanese prefecture who were over 45 years of age underwent a mass screening for prostatic disease that used the Hybritech (Tandem(R)RIA) kit, and the prostate volume was estimated by transabdominal ultrasonography. Differences among several groups of men according to prostate volume and age were examined by multiple comparisons using ranks. When some subjects visited several times, the data of the first visit were adopted only. The total number of individual subjects in this study was 589 men. The multiple comparisons using ranks and 10-year age brackets revealed that the levels of PSA showed significant differences between only two pairs of groups stratified by age. In contrast, the levels of PSA showed significant differences among seven pairs of groups stratified by the prostate volume according to 10-ml brackets. When a logarithmic transformation of the serum levels of PSA was used, the results showed the same tendencies. From the results of the present study, it can be said that the PSA reference range calculated with stratified prostate volume might be more useful in the detection of prostate cancer than that calculated with stratified age.

Aged↗

Osteopontin expression in prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: Osteopontin (OPN), a secreted adhesive glycoprotein, has been shown to be produced in excessive amounts in a variety of experimental models of malignancy. Increased levels of OPN exist in blood from the lungs, breasts, and gastrointestinal tracts of cancer patients with metastases. However, there have been no reports on the expression of OPN in human urological malignancies. The present study investigates the presence of OPN in adenocarcinoma of the human prostate and in benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Using prostate tissue from 34 patients with primary prostate cancer, 13 patients with prostate cancer after having undergone hormonal therapy, and 12 patients with BPH, formalin-fixed paraffin sections were prepared. Specimens were obtained by needle biopsy or radical prostatectomy. Immunohistochemical staining (ABC method) was then performed. Staining was divided into either negative or positive categories. RESULTS: Positive staining of OPN was observed on cancer cells and macrophages in 52.9% of the primary prostate cancers and 14.5% of the prostate cancers after hormonal therapy. In BPH specimens, 66.7% of the cases displayed positive staining of OPN. The staining level of OPN showed no correlation with serum prostate-specific antigen, but did correlate with stage, differentiation, and Gleason's score. CONCLUSIONS: The result postulates that the expression of OPN is an indicator of cell differentiation; however, it cannot be used as a marker of malignancy in prostate cancer.

Adenocarcinoma↗

Evaluation of prostate-specific antigen in untreated prostatic carcinoma.

A study was performed on 290 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic cancer. The upper limit of normal was 5.0 micrograms/l as determined in 110 elderly hospitalized males (mean age 62 years) without urological complaints. Of the 106 patients with BPH, 33% had raised values above 5.0 micrograms/l. Values above 10 micrograms/l were found in 18 BPH patients. A positive correlation was found between prostate volume (grams of tissue removed during transurethral resection) and preoperative PSA levels (r = 0.55, n = 106, p less than 0.001). PSA levels above 10 micrograms/l were found in 4% of BPH patients with a prostate volume of less than 20 g (n = 54), in contrast with 45% of patients with a prostate volume above 40 g (n = 20). The sensitivity of this PSA assay (cutoff level 10 micrograms/l) as established in 74 prostate carcinoma patients was 31% for category T0 (n = 13), 56% for category T1-2 (n = 16), 75% for category T3-4 (n = 20) and 100% for category M1 or N1-4 (n = 25). In an earlier study prostatic acid phosphatase (PAP) was measured in these same samples. PSA appeared to be much more sensitive than PAP. Seventeen of the 74 prostatic carcinoma patients (23%) had normal PAP levels but their PSA values were raised above 10 micrograms/l, while in only 2 patients an increased PAP level was combined with a normal PSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Serum concentration of prostate-specific antigen in relation to prostate volume in 50 healthy middle-aged men.

Fifty men without symptoms of prostatic disease, aged 40 to 66 years, were studied with respect to serum concentration of prostate-specific antigen (PSA) and volume of the prostate gland. PSA was determined with two immunometric assays, one using a radioactive label, the other a nonisotopic label. Prostate volume was determined by transrectal ultrasound examination using two different modes of evaluation and assessed by rectal examination. The simpler "ellipsoid method" underestimated the volume by 20% compared to planimetry of several sections but they were well correlated to each other. It was found that prostate volume increased by 0.4 ml per year of age increase. There was a curvilinear relationship between serum PSA concentration and prostate volume determined by ultrasound; no statistically significant relationship was found between PSA concentration and prostate volume by rectal examination. The results indicate that the diagnostic value of serum PSA, for prostatic malignancy, will increase if values are related to prostate volume determined by ultrasound examination.

Adult↗

[Transurethral resection for prostatic adenoma larger than 100 ml--preoperative treatment with interstitial laser coagulation of the prostate plus chlormadinone acetate as a treatment maneuver for safer operations].

Between August 1985 and March 2004, we performed transurethral resection of the prostate (TURP) in 18 patients with benign prostatic hyperplasia (BPH) whose prostatic volume was larger than 100 ml. We divided the patients into two groups. Group A consisted of a total of 14 cases: 10 cases whose mean prostate volume was 114 ml (100 to 137 ml) and 4 cases whose prostate volume was not measured before TURP but whose mean resected prostatic tissue weight was 113 g (105 to 118 g). Group B consisted of 4 cases whose mean prostate volume was 110 ml (101 to 133 ml). Patients in group B underwent interstitial laser coagulation of the prostate (ILCP) followed by oral chlormadinone acetate (CMA) therapy (50 mg/day); TURP was performed 6 months later, once the prostate volume had shrunk to an average of 76 ml (66 to 91 ml). Mean resected weights and operation times were: group A, 93.1 g, 66.3 min; group B, 60.5 g, 55.7 min. There were 12 blood transfusion cases (85.7%; intraoperative) in group A, and 1 (25.0%; POD 1) in group B. Accordingly, this preoperative treatment was considered a safer method of TURP for BPH 100 ml or more. There were no cases of TURP syndrome or death in either group.

Aged↗

Immunohistochemical investigation of different cytokeratins and vimentin in the prostate from the fetal period up to adulthood and in prostate carcinoma.

From the fetal period up to puberty the immature epithelium of the prostate glands, the prostatic ducts, the ejaculatory ducts and the seminal vesicles as well as the urothelium of the prostatic urethra are extensively positive for different keratin antibodies (antibody against keratins from human stratum corneum, broadly reacting antibody "AE1 and AE" and antibodies against the keratins 7, 8, 18 and 19) immunohistochemically. The epithelium of the ejaculatory ducts and seminal vesicles in addition regularly exprimates vimentin which is found in the epithelium of the prostate glands focally. During puberty, the immature epithelium of the prostate glands differentiates into the two cell types basal cell and secretory epithelium which differ immunohistochemically: Keratins from human stratum corneum are exclusively demonstrable in the basal cells, the keratins 8 and 18 only in the secretory epithelium. For keratin 7, 19 and the antibody "AE1 and AE3" both cell types are positive. Keratin 7 is demonstrable only focally. The secretory epithelium partly co-exprimates keratins and vimentin. Prostatic carcinomas of different grades virtually contain no keratins from stratum corneum. All other keratins are found in variable extension in the vast majority of the tumors independent of the differentiation. Vimentin is positive mostly focally in about 50% of the tumors. Prostatic carcinoma and the secretory epithelium of the prostate glands share identical immunohistochemical features and differ from the basal cell by several markers. This indicates that prostatic carcinoma rather derives directly from the secretory epithelium than from the basal cell.

Adolescent↗

[Measurement of serum prostatic acid phosphatase (PAP) by Delfia PAP Kit using europium and clinical evaluation in patients with prostate cancer].

Fundamental and clinical studies of serum prostatic acid phosphatase (PAP) detected by a Delfia PAP kit were performed. The system is a time-resolved fluoroimmunoassay using europium as a tracer. The lower limit of detection was 0.2 ng/ml. Sera from 54 patients with prostate cancer, 20 with benign prostatic hypertrophy, 20 with urological malignancies other than prostate cancer and 140 adult males over 46 years old were determined. From the mean + 2 S.D. of serum PAP values obtained on the adult males, 1.5 ng/ml was considered as the upper normal level of adult males. By calculating the efficiency and ROC curve using the PAP values of prostate cancer and benign prostatic cancer, 2.5 ng/ml was decided as a cut-off value of this kit. The positive rates of adult males, prostate cancer, benign prostatic cancer and urological malignancies other than prostate cancer were 0.7%, 65%, 20% and 10%, respectively. The sensitivity of stage A2, B2, C and D1 + D2 was, 0%, 0%, 64% and 83%, respectively. The efficiency of the Delfia PAP kit was 52% and that of the Markit M PA kit was 71%. The correlation between the values assayed with the Delfia PAP kit and the Dinabot PAP kit was very high; the value obtained with the Delfia PAP kit was about 80% of that obtained with the Dinabot PAP kit.

Acid Phosphatase↗

Consistent expression of an epithelial cell adhesion molecule (C-CAM) during human prostate development and loss of expression in prostate cancer: implication as a tumor suppressor.

Cell adhesion molecules have been suggested to function as tumor suppressor molecules. We have been studying one of the epithelial cell adhesion molecules (C-CAM), which belongs to the immunoglobulin gene superfamily. Transfection of a C-CAM cDNA expression vector into a highly tumorigenic human prostate cancer cell line (PC-3) suppresses tumor formation in nude mice. Alternatively, reducing C-CAM expression levels in the nontumorigenic rat prostate epithelial cell line NbE by the antisense expression vector markedly increases tumorigenicity of NbE cells in nude mice. These results suggest that C-CAM may be a tumor suppressor in prostate cancer. In this study, we examined the relationship between C-CAM expression during human prostate development and neoplastic progression by immunohistochemical staining of frozen sections. C-CAM predominantly localized on the plasma membrane of the basal cell layer in both the fetal and normal adult prostate gland. However, an overall decreased staining was seen in benign prostatic hyperplasia and high grade prostatic intraepithelial neoplasia. Furthermore, C-CAM was not detected in prostate carcinomas. Thus, a decrease in C-CAM expression may be an early event in hyperplastic/neoplastic transformation. These observations support the suggestion that C-CAM is a tumor suppressor in prostate cancer progression.

Antineoplastic Agents↗

[Prostate-specific antigen in patients with benign prostatic hyperplasia].

The authors examined 119 patients with the histological finding of benign prostatic hyperplasia (BPH). Before the planned operation of the prostate (transurethral resection or open prostatectomy) the authors examined in all patients the level of the prostate specific antigen (PSA) and the prostate volume by sonography. Of 119 patients 70 (58.8%) had elevated serum levels of PSA and in 35 (29.4%) the PSA level was higher than 10 ng/ml. The authors demonstrated a highly significant (p < 0.0001) linear relationship of the PSA serum level and volume of prostate in patients with BPH. Based on the results of simple regression analysis they elaborate an equation for the prostate volume: PSA ng/ml = (3.26 + 0.12 x volume of prostate (ml) +/- 8.44). By adding the value of the standard deviation of PSA the authors created an interval in which are most of the patients with BPH. The authors recommend supplementary examinations (transrectal sonography and biopsy of the prostate) in patients where there is a disproportion between the PSA level and the prostate volume.

Adult↗

[The digital rectal exam, prostate-specific antigen and transrectal echography in the diagnosis of prostatic cancer].

OBJECTIVES: This study analyzes the three available clinical methods in the diagnosis of prostate cancer (PC): digital rectal examination (DRE), serum prostate specific antigen (PSA) and transrectal ultrasound (TRUS), and attempts to establish the best system in the early detection of PC. METHODS: The findings of DRE, serum PSA and TRUS of the prostate in patients in which a TRUS-guided prostate biopsy was performed initially, and prostate surgery afterwards (TURP in 72%, radical retropubic prostatectomy in 20% and simple prostatectomy in 8%), are retrospectively analyzed. RESULTS: PC was eventually found in 50 patients (56%). Seventy-eight patients had an abnormal DRE, 44 of which had a final diagnosis of PC (sensitivity = 94%, specificity = 20.5%). Serum PSA levels were available in 60 cases before diagnosis. Levels > 4 ng/ml were found in 32 of 38 cases with PC (sensitivity = 84%, specificity = 31%). The TRUS finding with the highest positive predictive value (PPV) for PC was diffuse prostate heterogeneity (77.8%). When a hypoechoic nodule was seen in the prostate peripheral zone, PC was found in 53.7%. Different combinations of the three methods are analyzed, trying to increase the diagnostic capabilities of each isolated test. Transrectal ultrasound-guided prostate biopsy detected 44 (88%) of the 50 cases with PC, its negative predictive value being 86.7%. Prostate tissue valid for histologic diagnosis was obtained in 97% of the cases, and the predictive value of the true tumor grade was 84.1%. The general complication rate attained 3.4%, none being of the septic type. CONCLUSIONS: When parallel testing was examined (one or more tests being abnormal), the most efficient combination in the early detection of PC was when DRE was suspicious or serum PSA > 4 ng/ml (sensitivity = 95%, PPV = 62%). When at least two diagnostic tests were abnormal (serial testing), the most efficient combination to confirm the presence of this tumor was an abnormal TRUS and a serum PSA > 10 ng/ml (specificity = 86%, PPV = 88%).

Aged↗

[Reliability and use of prostate-specific antigen in the management of patients with prostatic cancer].

The authors are reporting the clinical importance of prostate specific antigen. They concluded that there are false positive and false negative cases. The prostate specific antigen is high in prostatic hyperplasia therefore the distinction between the two disease is impossible on basis of the prostate specific antigen. Prostate specific antigen shows the metastatic cases better [correction of worse] than prostatic acid phosphatase. But prostate specific antigen detects the changes of the clinical course of the disease well and shows the progression sooner. The authors have concluded that prostate specific antigen can not replace phosphatases and bone-scanning in the diagnosis and follow up of patients with prostate carcinoma.

Acid Phosphatase↗

Transurethral marsupialization of a medial prostatic cyst in patients with prostatitis-like symptoms.

PURPOSE: The results of transurethral marsupialization as treatment for medial prostatic cysts were assessed. MATERIALS AND METHODS: Between June 1992 and August 1994 we performed transrectal ultrasound on 704 patients with symptoms of bladder outlet obstruction or lower urinary tract symptoms and a medical prostatic cyst was found in 34 (5%). Transurethral marsupialization of the cyst via incision of the prostatic floor under transrectal ultrasound guidance was performed in 18 patients. Followup was 12 to 25 months (mean 18). RESULTS: Patients with a medial prostatic cyst complained of prostatitis-like symptoms (77%), scrotal pain (62%), impaired micturition (32%), small volume ejaculation (35%), painful ejaculation (24%), hemospermia (24%) and infertility (12%). After marsupialization of the cyst, symptoms resolved completely in 14 patients (78%), improved in 17 (94%) and did not improve in only 1 (6%). No complications of this procedure were noted. The 16 patients who did not undergo surgery still complain of prostatitis-like symptoms without evidence of bacterial prostatitis. CONCLUSIONS: We believe that a medial prostatic cyst can cause prostatitis-like symptoms and that marsupialization of the cyst can provide symptom relief in the majority of patients.

Adult↗

[Utility of prostate specific antigen (PSA) density in detecting prostate cancer in men showing gray zone serum PSA levels].

The efficacy of prostate specific antigen density (PSAD) in diagnosing prostate cancer was assessed in 98 patients with serum prostate specific antigen (PSA) levels between 2 and 10 ng/ml who had a pathological diagnosis made by prostate biopsy or transurethral resection of the prostate. Of the 98 patients, 22 (22%) had prostate cancer. The PSA (based on a cut-off value of 4.5 ng/ml) had a sensitivity and positive predictive value (PPV) of 82% and 38%, respectively, for diagnosing prostate cancer, while the results for PSAD (based on a cut-off value of 0.13) were 91% and 61%. The PSAD was more efficient than the PSA levels and was also superior to digital rectal examination (DRE) combined with transrectal ultrasonography (TRUS), for which the sensitivity and PPV were 73% and 39%, respectively. Six (11%) out of 57 patients who were normal on DRE and TRUS had prostate cancer. In these 57 patients, the PSA (cut-off value: 4.5 ng/ml) had a sensitivity of 50% and PPV while the values for PSAD (cut-off value: 0.13) were 83% and 36% respectively. The PSAD could effectively detect even impalpable prostate cancer not visible on TRUS.

Aged↗

Daily variability in human serum prostate-specific antigen and prostatic acid phosphatase: a comparative evaluation.

The daily variation of serum levels of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) was investigated simultaneously in 10 patients with osseous metastatic prostatic cancer, 10 patients with benign prostatic hyperplasia, and 10 volunteers without prostatic disease. Duplicate serum samples were obtained from all patients on the same day at 8 AM, 12 PM, 4 PM, and 8 PM. Statistical analysis (two-factor analysis of variance comparing time period to disease group) of the mean PSA and PAP levels at the four sampling times on all patient groups demonstrated no evidence of circadian rhythmic variation or any other distinct pattern for the observed sample times. Overall, the variability in PSA levels was significantly less than that observed for PAP. There was no significant difference in mean percent variation between patient groups (cancer, benign, and normal prostate glands) for both the PSA and PAP assays. Our data reveal that serum PSA measurements fluctuate unpredictably over the course of a day in patients with and without prostatic disease, but to a lesser extent than that seen for serum PAP values. These findings illustrate the potential inaccuracy of single determinations of serum PAP or PSA levels for monitoring disease recurrence and treatment response in patients with prostate cancer.

Acid Phosphatase↗

Prospective evaluation of prostate cancer detection by prostate-specific antigen-related parameters.

BACKGROUND: The diagnostic value of prostate-specific antigen (PSA) for differentiating prostate cancer from benign prostatic conditions is limited by its lack of specificity. Several PSA-related parameters have been suggested as enhancing the discriminatory power of total PSA values, but their clinical utility should be considered preliminary until established in a prospectively evaluated cohort. METHODS: In a prospective cohort study, results of ultrasound-guided biopsy and/or transurethral resection of the prostate gland were assessed in 706 consecutive Japanese men. The clinical usefulness of total PSA, free PSA, percentage of free PSA, PSA density (PSAD), PSA density for transition zone (PSADT) and gland volume for predicting prostate cancer was investigated using receiver operating characteristic (ROC) curve analysis in 16 different patient subgroups. RESULTS: Overall, 150 of the 706 patients (21.2%) had prostate carcinoma. The ROC curve analysis showed that PSAD and PSADT were more powerful predictors of prostate cancer than total PSA in most of the 16 patient subgroups tested. The improvement in performance was modest, however. No substantial difference was noted between PSAD and PSADT. Total gland volume did not significantly affect the performance of these parameters. The use of a PSAD threshold value of 0.11-10.15 ng/mL per cm3 (or a PSADT value of 0.23-0.27 ng/mL per cm3) would have avoided 24-48% (or, for PSADT, 34-40%) of unnecessary biopsies at the cost of missing 5-10% of detectable cancers in a patient subgroup with intermediate total PSA levels. The performance of free PSA and percentage of free PSA was worse than that of any other test in this study. This may be due to inappropriate handling of sera prior to measurement. CONCLUSIONS: The discriminatory potential of total PSA for predicting prostate cancer was modestly improved by the use of PSAD and PSADT. No substantial advantage of PSADT over PSAD could be demonstrated. Stringent and standardized storage conditions should always be maintained when applying free PSA-related parameters.

Aged↗

Prostate-specific antigen (PSA) in the management of 500 prostatic patients.

Blood samples from 500 patients with clinical prostatic symptoms were radioimmunoassayed with prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) kits. On the basis of histological data, directed by PSA results and other investigations, 200 prostatic cancers (adenocarcinomas), 276 benign prostatic hypertrophy (BPH), 16 cases of prostatitis, 5 cancers of the bladder, and 3 prostatodynias were diagnosed. All of the serum samples from prostatic cancer patients showed elevated PSA levels at diagnosis, whereas about 70% of these showed normal PAP values. The sensitivity of the PSA assay is 100% when 2.5 ng/ml is taken as the upper limit of normal. However, the specificity and the positive predictive value are better at 10 ng/ml: 99 and 79%, respectively. High PSA values alerted the clinician when diagnosing a cancer without symptoms on rectal or ultrasonographic examination (3%). In BPH, when the PSA level is between 2.5 and 10 ng/ml, a PSA control must be performed within 2 months. If PSA increases above 10 ng/ml, the risk of cancer has to be considered. In the follow-up, PSA is a better marker than PAP to detect disease progression and seems to constitute an evolutive tumor mass index. PSA is the most sensitive, the earliest, and the most prognostically reliable marker for diagnosis and follow-up of prostate cancer patients.

Acid Phosphatase↗

Clinical behaviour of prostatic specific antigen and prostatic acid phosphatase: a comparative study.

We assayed prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) serum levels in 1383 patients using a double antibody radioimmunoassay (RIA) I125. Establishing the upper normal limit in 10 ng/ml PSA and 2.5 ng/ml for PAP, the false positive results were only 1.9 and 5.1 percent in men with non-prostatic benign or malignant pathology and respectively 0 and 2.2 percent in women. We detected false positive levels for these two tumoral markers in 3.5 and 4.7 percent of patients with non-complicated benign prostatic hypertrophy, 64.8 and 19.2 percent in complicated benign prostatic hypertrophy, 24 and 16 percent in acute prostatitis and 3.3 percent in chronic prostatitis. The sensitivity in patients with prostate cancer was 87.2 percent for PSA and 64.1 percent for PAP, and there was a better correlation with PSA than PAP for tumoral spread and histological grading. Finally, clinical efficacy was higher with PSA and was no better when both markers were assayed.

Acid Phosphatase↗