Biomedical subjects

A Reissigl

Publications and source records attributed to A Reissigl.

At least 19 recordsLinked to original sources

PubMed2001

Prostate cancer mortality after introduction of prostate-specific antigen mass screening in the Federal State of Tyrol, Austria.

OBJECTIVES: To monitor the impact of screening in a natural experiment by comparing prostate cancer mortality in Tyrol, where prostate-specific antigen (PSA) testing was introduced at no charge, with the rest of Austria, where it was not introduced. METHODS: In 1993, PSA testing was made freely available to men aged 45 to 75 years in the Federal State of Tyrol, Austria. At least two thirds of all men in this age range have been tested at least once during the first 5 years of the study. Initially, only total PSA was measured, but free PSA measurement was added in 1995. The IMX assay was used. Digital rectal examination was not part of the screening examination. RESULTS: Significant migration to lower stages has been observed since the introduction of this screening program. A reduction in mortality rates in the rest of Austria from 1993 onward has occurred, with the reduction in Tyrol much greater; the mortality remained fairly constant between 1993 and 1995 and subsequently fell. The trends in prostate cancer mortality rates since 1993 differ significantly between Tyrol (P = 0.006) and the rest of Austria. On the basis of the age-specific death rates averaged from 1986 to 1990, the difference between the number of expected and observed deaths from prostate cancer in Tyrol was 22 in the group aged 40 to 79 years in 1998 and 18 the following year. CONCLUSIONS: These findings are consistent with the hypothesis that the policy of making PSA testing freely available, and the wide acceptance by men in the population, is associated with a reduction in prostate cancer mortality in an area in which urology services and radiotherapy are available freely to all patients. It is our opinion that most of this decline is likely to be due to aggressive downstaging and successful treatment and that any contribution from detecting and treating early cancers will only become apparent in the years to come.

Aged↗

PubMed2000

Prostate cancer screening in the Tyrol, Austria: experience and results.

This article summarises the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) and per cent free PSA as the initial test. Of the 21078 volunteers 1618 (8%) had elevated PSA levels. Of these men 778 (48%) underwent biopsies; 197 (25%) biopsies were positive for prostate carcinoma and 135 (17%) underwent radical prostatectomy. 95 were found to be organ-confined. A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection rate of organ-confined disease. 284/2272 men (13%) had elevated PSA levels and prostate carcinoma was detected in 62 men (3%). All patients underwent radical prostatectomy and histological examination revealed organ-confined tumour in all but 8 men. 98/340 men (29%) had biopsies positive for carcinoma; 28 of these patients (29%) had carcinoma that originated in the transition zone only. In the retrospective study, receiver operating characteristic curve analysis showed that by using a per cent free PSA of less than 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106/158 men (67%) with elevated PSA levels below 10.0 ng/ml were further evaluated and 37 (35%) prostate carcinomas were detected. By using a per cent free PSA of <22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120/465 men (26%) with total PSA levels between 1.25 and 6.49 ng/ml and a per cent free PSA<18% were further evaluated and 27 (23%) were found to have prostate carcinomas. Receiver operating characteristic curve analysis for PSA transition zone (TZ) density showed that by using a PSA transition zone density of >22 ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing a single carcinoma. In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a and T1b Grade 3 carcinoma was 2.3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. The rate of organ-confined tumours increased from 28.7% in 1993 to 65.7% in 1997. In this evaluation a new approach, to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rather than a single PSA cut-off point was developed. High total PSA levels, PSA density and PSA transition zone density correlated significantly with high Gleason scores, capsular penetration, a high percentage of cancer in the prostatectomy specimen and a high cancer volume. In this evaluation all of the 95 patients with PSA levels below 3.99 ng/ml who underwent radical prostatectomy showed clinically significant, organ-confined prostate cancer with negative surgical margins. The results of this evaluation suggest that older men have larger tumour volumes compared with younger men with the same PSA levels. These data suggest that PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ confined and potentially curable prostate cancer. Per cent free PSA and PSA transition zone density provide an additional diagnostic benefit over total PSA.

Age Distribution↗

PubMed1999

Correlation between preoperative predictors and pathologic features in radical prostatectomy specimens in PSA-based screening.

BACKGROUND: Measurement of percent free prostate-specific antigen (PSA), PSA density, and PSA-transition zone density (PSA-TZ density) in addition to total PSA is known to improve the specificity of PSA-based prostate cancer screening. We evaluated the ability of total PSA, percent free PSA, PSA density, and PSA-TZ density to predict pathologic features in radical prostatectomy specimens. METHODS: The levels of total PSA, percent free PSA, PSA density, and PSA-TZ density assessed prior to the diagnosis of prostate cancer were correlated with the pathologic findings in 102 prostate glands with cancer obtained at radical prostatectomy. The entire organs were examined histologically; Pearson correlation coefficients were used for statistical analysis. RESULTS: High levels of total PSA, PSA density, and PSA-TZ density correlated significantly with capsular penetration, high Gleason scores, and large cancer volumes in the prostatectomy specimens. Free PSA was found to correlate well with high Gleason scores, high percentages of cancer, and large cancer volumes, but not with capsular penetration. The four parameters were evaluated by means of logistic regression, which showed that only percent free PSA and total PSA were significant predictors of Gleason scores > or =7 and cancer volumes > or =0.5 cc. With regard to clinically insignificant cancers, only percent free PSA and the Gleason score obtained at biopsy were significant predictors. CONCLUSIONS: In men whose prostate cancers are detected by PSA-based screening, high total PSA levels in combination with low percent free PSA levels are suggestive of a potentially more aggressive type of prostate cancer. This may help both patient and clinician in selecting the most appropriate therapeutic approach.

Adult↗

PubMed1999

Prostate cancer screening in Tyrol, Austria: experience and results.

BACKGROUND: This article summarizes the experience and results of different prostate carcinoma screening projects using total prostate-specific antigen (PSA) and percent free PSA as the initial test. METHODS: The twelve projects studied included: (1) a mass screening study using PSA as the initial test in 21,079 volunteers; (2) an investigation of the usefulness of normal and age-referenced PSA cut-offs in 1,618 men; (3) a PSA-based screening study of 2,272 asymptomatic blood donors; (4) an investigation of the evidence and significance of transition zone carcinoma in 340 men with negative digital rectal examination findings; (5) determination of percent free PSA in one retrospective and two prospective studies to determine the appropriate cutpoints for percent free PSA; (6) evaluation of the diagnostic benefit of PSA transition zone density in 308 screening volunteers; (7) a study of the impact of PSA-based screening on the percentage of incidental prostate carcinoma in 1, 543 men undergoing transurethral resection of the prostate; (8) an evaluation of the changes in total PSA and pathologic stages in radical prostatectomy over 5 years in a PSA-based mass screening program; (9) a study evaluating the probability of having prostate cancer given the patient's age, total PSA and digital rectal examination findings; (10) an evaluation of the correlation between preoperative predictors and pathologic features in radical prostatectomy specimens; (11) an investigation of the correlation of total PSA with pathologic stage and tumor volume in patients undergoing radical prostatectomy with low PSA cut-off level, and (12) a study whether age has an impact on the extension of prostate cancer. RESULTS: (1) of the 21,079 volunteers, 1,618 (8%) had elevated PSA levels. Of these men, 778 (48%) underwent biopsies; 197 biopsies were positive for prostate carcinoma and 135 underwent radical prostatectomy. Ninety-five were found to be organ-confined. (2) A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection rate of organ-confined disease. (3) Of the 2,272 men, 284 had elevated PSA levels and prostate carcinoma was detected in 62 men. All patients underwent radical prostatectomy and histologic examination revealed organ-confined tumor in all but 8 men. (4) Ninety-eight of 340 men had biopsies positive for carcinoma; 28 of these patients (28.5%) had carcinoma that originated in the transition zone only. (5) In the retrospective study, receiver-operating characteristic curve analysis showed that by using a percent free PSA of 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106 of 158 men with elevated PSA levels <10.0 ng/ml were further evaluated and 37 prostate carcinomas were detected. By using a % free PSA of <22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120 of 465 men with total PSA levels between 1.25 and 6.49 ng/ml and a % free PSA <18% were further evaluated and 27 (22.5%) were found to have prostate carcinomas. (6) Receiver-operating characteristic curve analysis for PSA transition zone density showed that by using a PSA transition zone density of >22 ng/ml/cm3 as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing a single carcinoma. (7) In the prescreening era the incidence of T1a grade 1 and 2 carcinomas was 3.1% and the incidence of T1a grade 3 and T1b carcinoma was 2.3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. (8) The rate of organ-confined tumors increased from 28.7% in 1993 to 65.7% in 1997. (9) In this evaluation a new approach to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rath

Adult↗

PubMed1998

Improvement of specificity in PSA-based screening by using PSA-transition zone density and percent free PSA in addition to total PSA levels.

BACKGROUND: The clinical value of prostate-specific antigen (PSA) density in differentiating between prostate cancer and benign prostatic hyperplasia has been the subject of several studies. In this context the question has been raised about the diagnostic benefit of PSA transition-zone density (PSA-TZ density = total PSA/transition-zone volume) in the detection of prostate cancer. In the following study the value of PSA-TZ density alone and in combination with free PSA was investigated. METHODS: Between August 1995-May 1996, 308 first-line screening volunteers with elevated total PSA levels ranging from 2.5-10.0 ng/ml were evaluated. All patients underwent digital rectal examination, transrectal ultrasound, and transrectal ultrasound-guided biopsy of the prostate. Prior to these investigations, serum was obtained and total as well as free PSA levels were obtained. PSA transition-zone density (PSA-TZ density) was defined as follows: PSA-TZ density = total PSA/transition-zone volume. RESULTS: ROC curve analyses for PSA-TZ density showed that by using a PSA-TZ density of more than 0.22 ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided; ROC curve analyses for free PSA showed that by using percent free PSA <20% as a biopsy criterion, 45.5% of negative biopsies could be eliminated. When combining these two diagnostic tests, 54.2% of negative biopsies could be avoided. CONCLUSIONS: We conclude that PSA-TZ density, in addition to total and free PSA, is a new opportunity which renders it possible to calculate the likelihood of detecting prostate cancer on repeat biopsies in an individual patient.

Biopsy↗

PubMed1998

Transurethral ultrasound: evaluation of anatomy and function of the rhabdosphincter of the male urethra.

PURPOSE: A combined anatomic-sonographic study was undertaken to investigate whether the anatomical arrangement and the contractions of the rhabdosphincter of the male urethra could be visualized by transurethral ultrasound. Furthermore, this new technique was compared with standard urodynamic tests. MATERIALS AND METHODS: In 7 cadavers transurethral ultrasound was performed to define sono-morphological criteria of the rhabdosphincter, and the sonographic pictures were then compared to histological sections. In 48 patients the rhabdosphincter of the male urethra was investigated by transurethral ultrasound and urodynamic techniques. Of these patients 40 were completely continent after radical prostatectomy and 8 presented with urinary stress incontinence after transurethral resection of the prostate or radical prostatectomy. The decrease of the distance between the rhabdosphincter and the transducer during contraction served as quantitative parameter for the contractility of the muscle. RESULTS: The anatomical arrangement and contractions of the rhabdosphincter loop could be clearly visualized on transurethral ultrasound (during contraction the rhabdosphincter retracts the urethra, pulling it towards the rectum). Ultrasound showed scars in 3 patients with postoperative urinary stress incontinence, thinning of the muscle in 3 complete atrophy of the rhabdosphincter in 2 and minimal contractions of the rhabdosphincter in 1. Urethral closure pressures were decreased and decrease in rhabdosphincter-transducer distance was statistically significantly decreased in the incontinent patients. CONCLUSIONS: Our sono-morphological data and anatomical histological results strongly suggest that the rhabdosphincter constitutes the main component of the continence mechanism in post-prostatectomy patients. Unlike urethral pressure profiles, which can only reveal zones of higher intraluminal pressure between the bladder and the penile urethra, transurethral ultrasound is highly specific for measurement of the function of the rhabdosphincter.

Humans↗

PubMed1998

Measurement of serum prostate-specific membrane antigen, a new prognostic marker for prostate cancer.

OBJECTIVES: To describe current results with Western blot assay for prostate specific membrane antigen (PSMA) using 7E11.C5 antibody and the development of an additional antibody measurement for PSMA by a new sandwich immunoassay. METHODS: A population of patients from a screening group, from a difficult diagnostic group, from a pre- and postoperative radical prostatectomy group, and from a group with metastatic disease followed for a serial period, provided the serum values for a prospective assessment of PSMA by Western blot assay. A new monoclonal antibody was sought, reacting to the C-terminal region of PSMA in order to develop a sandwich radioimmunoassay. RESULTS: PSMA values in screened patients correlate with the more advanced stage of the cancers determined. In postprostatectomy patients, the PSMA value corresponds more with preoperative values and with the values of those with a poor clinical course. In difficult diagnostic cases, the PSMA value is increased, specifically in hormone-refractory cases and particularly in those cases judged by other criteria, such as the National Prostatic Cancer Project, to be in clinical progression compared with those judged to be in clinical remission. The level of PSMA value appears to be independent of homogeneous tumor volume and to be more related to that of prior hormone treatment, or to where prostate cancer cells can be documented to be outside the prostate. A new monoclonal antibody, 3F5.4G6, reacts with the extracellular domain of PSMA near the C-terminal region. This is in contrast to the previously measured antibody 7E11.C5, which reacts with an N-terminal epitope. 3F5.4G6 recognizes the same PSMA protein as does 7E11.C5. The epitopes are essentially at opposite ends of the molecule. The 3F5.4G6 antibody reacts with the LNCaP line but not with DU145, or PC3. These two antibodies to PSMA are well suited for use in a new sandwich immunoassay. CONCLUSIONS: PSMA provides a prostatic cancer serum test by using Western blot, which suggests a clinical prognostic value not seen with other markers. New antibodies, such as 3F5.4G6, reacting with the extracellular domain of PSMA combined with 7E11.C5, appear to offer an opportunity for a new sandwich immunoassay.

Antibodies, Monoclonal↗

PubMed1997

Prostate carcinoma screening in the county of Tyrol, Austria: experience and results.

BACKGROUND: This article summarizes the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) as the initial test and different diagnostic tests to improve specificity. METHODS: The seven projects studied included 1) a mass screening study using PSA as the initial test in 21,079 volunteers; 2) an investigation of the usefulness of normal and age-referenced PSA cutoffs in 1618 men; 3) a PSA-based screening study of 2272 asymptomatic blood donors; 4) an investigation of the incidence and clinical significance of transitional zone carcinoma in 340 men with negative rectal examination findings and clearly visible prostatic zones on three-dimensional transrectal ultrasound; 5) determination of percent free PSA in one retrospective and two prospective screening studies to define the optimal range of total PSA and determine the appropriate cutpoints for percent free PSA within this range; 6) evaluation of the diagnostic benefit of PSA transitional zone density in 308 screening volunteers; and 7) a study of the impact of PSA-based screening on the percentage of incidental prostate carcinoma diagnosed in 1543 men undergoing transurethal resection of the prostate. RESULTS: 1) Of the 21,078 volunteers, 1618 (8%) had elevated PSA levels. Of these men, 778 (48%) underwent biopsies; 197 biopsies (25%) were positive for prostate carcinoma and 135 patients underwent radical prostatectomy. Ninety-five of the 135 pathologically staged lesions (70%) were found to be organ-confined. 2) A PSA cutoff of 2.5 ng/mL in men age 45-49 years and of 3.5 ng/mL in men age 50-59 years with normal digital rectal examination findings resulted in an 8% increase in both the number of biopsies (66 of 778) and the detection rate of organ-confined disease. 3) Of the 2272 men, 284 had elevated PSA levels and prostate carcinoma was detected in 62 men. All patients underwent radical prostatectomy and histologic examination revealed organ-confined disease in all but eight men. 4) Ninety-eight of 340 men (28.8%) had biopsies positive for carcinoma; 28 of these patients (28.5%) had carcinoma that originated in the transitional zone only. 5) In the retrospective study, receiver operating characteristic curve analysis showed that by using a percent free PSA of 18% as a biopsy criterion in men with an elevated PSA serum level, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106 of 158 men with elevated total PSA values between 2.5 and 10.0 ng/mL were further evaluated and 37 prostate carcinomas were detected. By using a percent free PSA of < or =22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120 of 465 men with total PSA levels between 1.25 and 6.49 ng/mL, a percent free PSA of <18%, and normal digital rectal examination findings were further evaluated and 27 (22.5%) were found to have prostate carcinoma. 6) Receiver operating characteristic curve analysis for PSA transitional zone density showed that by using a PSA transitional zone density of >0.22 ng/mL/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing the detection of a single carcinoma. 7) In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a Grade 3 and T1b carcinoma was 2.3%, whereas in the years after the establishment of PSA-based screening the incidence was 4.6% and 1.03%, respectively. CONCLUSIONS: These data suggest that PSA-based screening increases the detection rate of clinically significant and organ-confined tumors. Percent free PSA and PSA transitional zone density provide an additional diagnostic benefit over total PSA.

Age Factors↗

PubMed1997

Basic fibroblast growth factor levels in cancer cells and in sera of patients suffering from proliferative disorders of the prostate.

BACKGROUND: Both benign and malignant growth of the prostate depend on the induction of a microvasculature. Basic fibroblast growth factor (bFGF), a potent angiogenic factor, is thought to play an important role in this process. METHODS: bFGF expression in prostatic carcinoma was assessed by ELISA, reverse transcription polymerase chain reaction, and immunohistochemistry. RESULTS: DU-145 and PC-3 tumor cells produced bFGF. Almost 80-90% of it was localized in the cytoplasm, and 10-20% was associated with extracellular matrix components. Immunohistochemical analysis of prostatic tissue sections showed that cancer cells stained more intensively as compared to putatively healthy epithelium. In prostate cancer patients, mean bFGF serum levels were significantly elevated when compared to a healthy control group (6.64 pg/ml vs. 1.28 pg/ml). Serum bFGF levels did not correlate with any other clinical marker such as PSA, tumor stage, or grade. Four out of five patients who progressed to a more advanced stage showed an increase in serum bFGF levels. CONCLUSIONS: These results suggest that increased bFGF release may be associated with a more aggressive tumor phenotype.

Adult↗

PubMed1997

Are contact laser, interstitial laser, and transurethral ultrasound-guided laser-induced prostatectomy superior to transurethral prostatectomy?

BACKGROUND: In order to assess the value of various new therapeutic modalities in the management of benign prostatic hyperplasia (BPH), we performed a prospective study comparing transurethral resection of the prostate (TURP) to contact Laser, interstitial Laser, and transurethral ultrasound-guided laser-induced prostatectomy (TULIP). METHODS: The following parameters were evaluated preoperatively as well as 3, 6, and 12 months after surgery: prostatic volume, urinary flow rate, postvoid residual volume, and the AUA symptom score. The diagnosis of bladder outlet obstruction was established preoperatively by means of pressure/flow studies which were repeated 1 year after the operation. RESULTS AND CONCLUSIONS: In conclusion, TURP is still the gold standard in the treatment of BPH. The results of TULIP, contact laser, and interstitial laser are about the same. The time intervals within which the patients become free of symptoms, however, vary widely. Contact laser is limited to prostates below 50 cc, while interstitial laser is ideal for patients in poor general health who present with large prostates. Furthermore, our results demonstrate that the only reliable data for determining the degree of posttherapeutic disobstruction can be provided by urodynamic investigations including pressure/flow diagrams.

Humans↗

PubMed1997

Improvement of prostate cancer screening by determination of the ratio free/total PSA in addition to PSA levels.

BACKGROUND: The measurement of prostate specific antigen (PSA) is widely used in screening programs for early detection of prostate cancer. However the specificity for cancer detection is limited because serum PSA is also elevated in patients with benign prostatic-hyperplasia (BPH) and/or prostatitis. It has been shown recently, that the ratio of free/total PSA in serum is lower in malignant prostatic disorders than in non-malignant ones and therefore might be a parameter to improve screening specificity. In a retrospective study, we tested whether free/total PSA helps to distinguish between BPH and prostatic carcinoma in men with elevated serum PSA. METHODS: A total of 266 men have been identified with age-specific elevated serum PSA levels using a conventional PSA determination kit. Subsequently their disease was proven by biopsies. Free and total PSA levels in these serum samples were measured using the DELFIA PSA dual label free/total PSA kit. RESULTS: The mean free/total PSA of 64 patients with prostate cancer was 0.10 and was significantly (P = 0.001) different from the mean free/total PSA of 202 men who were histologically free of cancer, which was 0.17. Receiver-operating-characteristic curve (ROC) analysis showed that using a free/total PSA ratio of 0.18 as a biopsy criterion in men with an elevated PSA serum level, 37% of the negative biopsies could be eliminated while still detecting 94% of all carcinomas. CONCLUSIONS: These results show that the ratio of free/total PSA is a useful determination and can improve specificity of prostate cancer screening.

Aged↗

PubMed1997

Frequency and clinical significance of transition zone cancer in prostate cancer screening.

Approximately 20% of prostate cancers originate in the transition zone (TZ). Although transrectal ultrasound (TRUS) and systematic biopsies have improved peripheral zone (PZ) cancer diagnosis, additional biopsies directed into the TZ may further improve cancer detection. To evaluate the frequency and clinical significance of TZ cancers, we added two TZ biopsies to the routinely performed sextant biopsies. Three hundred forty patients (aged 45-75) from our prostate-specific antigen (PSA) screening study (21,078 volunteers) with negative rectal examination findings underwent systematic and TZ biopsies with three-dimensional ultrasound equipment. All patients had elevated PSA levels according to age-specific reference ranges. Ninety-eight of 340 men (28.5%) had biopsies positive for cancer. Of these 98 cancers, 28 (28%) originated in the TZ only and 5 (5%) were located in the TZ as well as the PZ. Eight men showed TZ abnormalities on ultrasound images, of whom four had biopsies positive for TZ cancer. The TZ cancers detected were pathologically significant in 96% (27 of 28). Seventy-one percent (20 of 28) of pathologically staged cancers were found to be organ confined and all combined TZ and PZ cancers were advanced tumors. We conclude that TZ biopsies enhance the cancer detection rate in prostate cancer screening and should therefore be added to the routinely done sextant biopsies in men with PSA elevation and normal digital rectal examination findings.

Aged↗

PubMed1997

PSA-based screening for prostate cancer in asymptomatic younger males: pilot study in blood donors.

BACKGROUND: The efficacy and success of a screening program for prostate cancer in young and healthy asymptomatic volunteers are described. METHODS: In the present study, prostate specific antigen (PSA) samples obtained from 2,272 males (aged 40-65 years) who donated blood at the local Red Cross Blood Bank were evaluated. Two groups of donors were distinguished, which were investigated in different ways. Group 1 comprised individuals aged 40-49 years (n = 568), while group 2 consisted of males aged 50-65 years (n = 1,704). Volunteers in group 2 who had PSA levels greater than 4 ng/ml (n = 302) were referred for ultrasound guided biopsy irrespective of findings on digital rectal examination (DRE). In group 2, individuals with PSA levels exceeding 4 ng/ml and positive DRE findings biopsy specimen was ordered (n = 2). In patients with unremarkable findings on DRE, serum PSA was determined 1 year later and in case of more than 20% increase in the PSA level biopsy was obtained under ultrasound guidance. RESULTS: The biopsy specimen yielded prostatic carcinoma in 58 patients in group 1. As a screening test, serum PSA determination was superior to digital rectal examination. On digital palpation only 2 presented with abnormal prostates. These 58 patients underwent radical prostatectomy and histological examination revealed organ-confined disease in all but 8. In group 2, in 4 of 12 males the biopsy specimen yielded prostatic carcinoma. CONCLUSIONS: This study shows that PSA measurement in blood donors is a useful method for recruiting screening volunteers, and therefore represents an additional possibility for early detection of prostate cancer in asymptomatic younger males. Furthermore, it represents an effective tool for following relatively young patients known to have a significant risk of prostate cancer.

Adult↗

PubMed1997

Microvessel density in core biopsies of prostatic adenocarcinoma: a stage predictor?

Microvessel density was recently reported to be an independent correlate of tumour stage in whole mount prostatectomy specimens. This prompted an investigation of whether the quantitation of tumour microvessels could also be reliably applied to prostatic core biopsies, as a presurgical determinant of local tumour extension. The study was performed on a series of 46 unselected patients with prostatic adenocarcinomas undergoing radical prostatectomy. Intratumoural microvasculature was highlighted immunohistochemically using an antibody against CD31 and subsequently evaluated at x 400 magnification in both biopsies and corresponding prostatectomies. The highest microvessel count was reported for each case. Ten cases (22 per cent) had to be excluded because of insufficient measurable tumour areas in core biopsies. The remaining 36 cases (16 pT2; 20 pT3) showed a high degree of correlation between microvessel density in biopsies and prostatectomies (P < 0.0001). Similarly, pre- and post-operatively determined microvascular counts correlated well with tumour stage (P < 0.0001). Furthermore, the median microvessel density in core biopsies and tumours, i.e., 34, distinguished well between organ-confined and organ-extending tumours (positive predictive value for pT3 tumours 94.4 per cent; sensitivity 85 per cent). These data indicate that the evaluation of microvessels in core biopsies, eventually combined with other parameters, could be a reliable method for the individual prediction of the post-surgical tumour stage of prostatic adenocarcinoma.

Adenocarcinoma↗

PubMed1997

Posttraumatic posterior urethral stricture repair: anatomy, surgical approach and long-term results.

PURPOSE: We describe the anatomy, surgical approach and long-term results of posterior urethral stricture repair. MATERIALS AND METHODS: Between 1975 and 1991, 86 patients underwent surgery for posttraumatic posterior urethral stricture. In 65 patients the urethral lesion was corrected by 1-stage reconstructive surgery via the perineal approach. In 21 patients the urethra was reconstructed with a 2-stage procedure. In an anatomical study the course of the urethra through the pelvic floor was investigated and the concomitant structures were dissected. According to the anatomy a perineal approach was used in 7 male adult cadavers. RESULTS: Due to the optimized anastomotic technique urinary flow rates of more than 20 ml. per second could be achieved in 29 of all 42 patients followed. Only 6 of these patients had peak urinary flow rates of less than 15 ml. per second. No patient had any recurrent strictures at the anastomotic site that would have required surgical revision. CONCLUSIONS: Our results suggest that adequate primary care and the perineal approach combined with an exact anastomosis technique are essential for successful treatment of posttraumatic strictures of the posterior urethra.

Adult↗

PubMed1997

Prostate-specific antigen as a screening test. The Austrian experience.

PSA-based screening substantially increases the prostate cancer detection rate and the percentage of organ-confined tumors. It appears that there is some benefit from screening for prostate cancer because of the increased amount of potentially curable disease discovered and the fact that 96% of the pathologically staged tumors detected have histologic features associated with aggressive cancer. Additional evidence that nearly all tumors detected on the basis of initial PSA screening are apt to be clinically significant may be derived from the information that PSA-based screening decreases the incidence of incidental A1 grade III and A2 tumors but does not increase the detection of clinically insignificant A1 grade I and II tumors. At this time, PSA represents the most effective and valuable tool to detect early prostate cancer; therefore, PSA should be used to improve early diagnosis of prostate cancer. Some advances have been made with the introduction of age-specific reference ranges and the ability to measure free to total PSA ratios. The data presented support the clinical usefulness of age-specific reference ranges for serum PSA. Calculation of the free to total PSA ratio is valuable in deciding which screening volunteers require further evaluation, increases the specificity of PSA screening, and as demonstrated may be useful in deciding which patients with isolated PIN should undergo repeat biopsies. Based on these facts, PSA truly can be described as the most important and useful marker for adenocarcinoma of the prostate. Based on these encouraging results and the obligingness of the social insurances, we will be able to continue PSA screening for early detection of prostate cancer for all concerned Tyrolean men in the future.

Austria↗

PubMed1996

Evaluation and comparison of two new prostate carcinoma markers. Free-prostate specific antigen and prostate specific membrane antigen.

BACKGROUND: Two new prostate cancer markers, free-prostate specific antigen (f-PSA) and prostate specific membrane antigen (PSMA) were recently introduced. This report summarizes a prospective two-year multicenter test of their diagnostic or prognostic capabilities. Total PSA was also measured. METHODS: There were four clinical groups studied: (1) 226 individuals from a screening project undergoing ultrasound and biopsy evaluation had markers obtained: (2) 68 patients suspected of having prostate cancer and undergoing 2 or more biopsies had the markers obtained on multiple occasions: (3) 100 patients undergoing radical prostatectomy had markers obtained pre- and post-operatively: and (4) 31 patients with metastatic prostate cancer each had multiple samples for marker assay obtained over a 2-year period. In all, 465 patients had one or more samples obtained and studied. RESULTS: Free-PSA affords little additional diagnostic advantage compared with total PSA in the screening population. The receiver operating characteristic curves for diagnostic accuracy were ranked: (1) PSA density; (2) total PSA; (3) f-PSA; and (4) PSMA, PSMA showed the best correlation with stage of the primary tumor in the screened group. In the multiple negative biopsy group, f-PSA varied from 12 to 21%. PSMA values were evaluated in all histologic categories. PSA density was > or = 0.15 in all categories. In the prostatectomy cases PSA values postoperatively were quite low in Stage II; f-PSA was of no value. Later, f-PSA was increased in association with elevated total PSA values. Mean PSMA values were above normal in all postoperative time periods except in Stage III patients at 6 months to 1 year postoperatively. PSA densities were all > or = 0.15. In patients with metastatic carcinoma, elevated PSMA values correlated best with a poor prognosis (clinical progression), as has been described. CONCLUSIONS: These data suggest that f-PSA values do not provide additional diagnostic benefit compared with total PSA in screening populations, in the presence of suspected cancer, postprostatectomy, or in metastatic disease. PSMA is of prognostic significance, especially in the presence of metastatic disease, and correlates well with the stage of disease in cancers detected in a screened population.

Antigens, Neoplasm↗

PubMed1996

Inhibitory effects of the nucleoside analogue gemcitabine on prostatic carcinoma cells.

Gemcitabine (2',2'difluoro-2'deoxycytidine, dFdC) is a synthetic antimetabolite of the cellular pyrimidine nucleotide metabolism. In a first series of in vitro experiments, the drug showed a strong effect on the proliferation and colony formation of the human androgen-sensitive tumor cell line LNCaP and the androgen-insensitive cell lines PC-3 and DU-145. Maximal inhibition occurred at a dFdC concentration as low as 30 nM. In contrast to the cell lines which were derived from metastatic lesions of prostate cancer patients, no inhibitory effects were found in normal primary prostatic epithelial cells at concentrations up to 100 nM. The effect of gemcitabine was reversed by co-administration of 10-100 microM of its natural analogue deoxycytidine. In view of a future clinical application of this anti-tumor drug in advanced prostatic carcinoma, we have compared the effect of gemcitabine on prostatic tumor cells with that on bone marrow granulopoietic-macrophage progenitor cells, because neutropenia is a common side effect of gemcitabine treatment. The time course of action on the two kinds of cells was markedly different. Colony formation of tumor cells was inhibited by two thirds at a gemcitabine concentration of about 3.5 nM. The same effect on granulopoietic-macrophagic progenitor cells required a concentration of 9 nM. Co-administration of deoxycytidine to gemcitabine-treated tumor cell cultures completely antagonized the effect of gemcitabine whereas addition of deoxycytidine after 48 hr of gemcitabine treatment could not prevent gemcitabine action on the tumor cells. In contrast, more than half of the granulopoietic-macrophagic progenitor cells could still be rescued by deoxycytidine administration after 48 hr. These findings and the marked difference in the susceptibility of neoplastic and normal prostatic cells suggest that gemcitabine is a promising substance which should be further evaluated as to its efficacy in the treatment of advanced prostatic carcinoma.

Antimetabolites, Antineoplastic↗