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Biomedical subjects

P Hammerer

Publications and source records attributed to P Hammerer.

At least 19 recordsLinked to original sources
PubMed2001

A multicenter clinical trial on the use of alpha1-antichymotrypsin-prostate-specific antigen in prostate cancer diagnosis.

BACKGROUND: The aim was to evaluate the clinical performance of alpha(1)-antichymotrypsin prostate-specific antigen (PSA-ACT) for early diagnosis of prostate cancer (PCa) in a multicenter trial. METHODS: Three hundred sixty-seven white men with PCa and 290 with benign prostatic hyperplasia (BPH) with tPSA concentrations between 2 and 20 microg/L were analyzed. The Elecsys system 2010 (Roche Diagnostics, Germany) was used for determination of total PSA (tPSA) and free PSA (fPSA). The PSA-ACT test was a prototype assay used on the ES system (Roche Diagnostics). RESULTS: The median concentrations of tPSA (PCa: 8.43 microg/L vs. BPH: 6.60 microg/L) and PSA-ACT (8.30 microg/L vs. 6.46 microg/L) were significantly different, respectively. The median ratios of fPSA/tPSA (PCa: 12% vs. BPH: 16%) and PSA-ACT/tPSA (98% vs. 95%) were significantly different. Receiver operating characteristics (ROC) analysis for discrimination between PCa and BPH (tPSA between 2 and 20 microg/L) was performed with 252 matched pairs and showed that the area under the curve (AUC) of the ratio fPSA/tPSA (0.66) was significantly different from tPSA (0.50) and PSA-ACT (0.52). PSA-ACT alone or the ratio PSA-ACT/tPSA (0.56) were not significantly different from tPSA. For tPSA between 4 and 10 microg/L (n = 145 pairs), the AUC of the ratio fPSA/tPSA (0.65) was significantly higher than tPSA (0.50) and PSA-ACT (0.54). Significant differences between tPSA and PSA-ACT or PSA-ACT/tPSA (0.56) were not found. CONCLUSIONS: The determination of PSA-ACT as well as the PSA-ACT/tPSA ratio did not improve the diagnostic impact in patients undergoing evaluation for PCa compared to fPSA/tPSA ratio.

Adult↗
PubMed2001

[Nerve-sparing radical retropubic prostatectomy. Results of a patient survey].

Improved selection criteria have led to an increasing number of nerve-sparing radical retropubic prostatectomies (RRP) in patients with clinically localized prostate cancer. The results based on patient questionnaires regarding postoperative erectile function are described. Between January 1992 and March 1999, 366 patients (mean age: 62.5 years) underwent uni- or bilateral nerve-sparing RRP at our institution. For evaluation of postoperative patient-reported rates of sexual and erectile function, a questionnaire was used after a follow-up of at least 12 months. Data of five operation periods were analyzed. The results of the unilateral procedure for the five operation periods revealed consistent rates of 13-29% for erections sufficient for intercourse. Bilateral nerve-sparing procedures were almost exclusively performed in periods 3 to 5; only four patients from period 2 underwent the bilateral procedure. The rates of intercourse-sufficient erections were 25% (period 2), 61% (period 3), 50% (period 4), and 52% (period 5), respectively. The results of the unilateral procedure were disappointing. However, the bilateral nerve-sparing method achieved much better results inasmuch as about 50% of the patients reported recovery of erections sufficient for sexual intercourse.

Aged↗
PubMed2001

Significance of high-grade prostatic intraepithelial neoplasia in needle biopsy specimens.

OBJECTIVES: To examine the significance of high-grade prostatic intraepithelial neoplasia (HGPIN) in biopsy specimens. METHODS: We performed sextant biopsies on a series of 83 cystoprostatectomy specimens removed for bladder cancer. For each case the number of foci and volume of both HGPIN and prostate cancer were assessed in the prostatectomy specimens and compared with the number of biopsy specimens involved by HGPIN. RESULTS: We identified HGPIN in 82 (99%) of 83 prostatic glands, whereas prostate cancer was found in 41 cases (49%). Corresponding sextant biopsies harbored both HGPIN and prostate cancer in 6 cases (7%), whereas only HGPIN was diagnosed in 29 sextant biopsies (35%). There was a positive correlation between the number of biopsy specimens containing HGPIN and the volume and multifocality of HGPIN in the corresponding prostatic glands. Prostates with HGPIN on sextant biopsy contained prostate cancer significantly more often when compared to cases with no HGPIN on sextant biopsy. Frequency of concurrent prostate cancer was higher in cases with two or more biopsy specimens containing HGPIN than in cases with only one such biopsy specimen, but case numbers of these categories were too small to render this difference statistically significant. CONCLUSIONS: The presence of HGPIN in sextant biopsies is a significant predictor of concurrent prostate cancer. Multifocality of HGPIN is a useful parameter in assessing the extent of HGPIN in the corresponding prostates. Its value in predicting a significantly increased risk of concurrent prostate cancer needs to be further investigated in larger case studies.

Adult↗
PubMed2000

[Prognostic markers for prostate cancer].

Careful consideration of therapy for prostate cancer needs an accurate analysis of prognostic markers to estimate success and benefit for the patient. Prognosis of prostate cancer is determined by the proportion of high grade cancer, many usually utilized prognostic characteristics were rejected by multivariate analysis as no independent prognostic information was delivered. For planning therapy it is crucial to estimate the proportion of high grade cancer as exact as possible. A standardized biopsy technique combined with a quantified analysis of the biopsy cores is most helpful to achieve this goal. The prognostic value of molecular biological and other factors is object of research, only a combination of some of these factors could be demonstrated so far to be superior to the estimation of the proportion of high grade cancer. However, at present their routine use in daily practise is precluded by a high technical and financial expense.

Biomarkers, Tumor↗
PubMed2000

[Chemoprevention of prostatic carcinoma].

Chemoprevention of prostate cancer is the administration of agents to prevent, inhibit, or delay progression of prostate cancer. Asian men have a much lower incidence of prostate cancer than men in Europe or the USA. Asian food includes low-fat, high-fiber diets, which provide a rich supply of weak dietary estrogens. These estrogens have been proposed as chemopreventive agents. In addition to their estrogenic activity, many of these plant compounds can interfere with steroid metabolism and bioavailability and can also inhibit enzymes, such as tyrosine kinase or topoisomerase, which are important for cellular proliferation. In addition, nutritional factors such as reduced fat intake, vitamin E, vitamin D, and selenium may have a protective effect against prostate cancer. The fact was proven in large epidemiological studies as well as experimental observations. In the animal model, the progression of established tumors can be inhibited by these agents. A number of studies to investigate the effect of possible chemopreventive agents for men at high risk of prostate cancer are established. End points for evaluation are mainly based on changes in PSA, changes of histological precursors, or time of onset of clinical disease. The concept of chemoprevention in prostate cancer might have a significant impact on the incidence and mortality of this disease.

Animals↗
PubMed2000

Stage migration in clinically localized prostate cancer.

OBJECTIVES: To determine whether migration of pathological tumor stages in patients with clinically localized prostate cancer exists and whether this is due to an increasing frequency of treating patients with clinically insignificant cancer. METHODS: 1,063 radical retropubic prostatectomies were performed in patients with clinically localized prostate cancer in one institution within 7.5 years (from 1992 until June 1999). All specimens were prospectively processed according to the Stanford protocol. These were then analyzed regarding the migration of pathological tumor stages and cancer volumes. RESULTS: Within the observation period, the annual rate of radical retropubic prostatectomies increased by 225% from 69 to 224 cases. The authors noted a decline of advanced tumor stages (from 65 to 40%) and an increase in pathological T2 tumors (from 30 to 55%). The rate of small cancers (<0.5 cm(3)) remained stable between 2 and 5% over the last 5 years. CONCLUSION: The data confirm trends which were observed in large US centers with increasing detection and treatment of localized prostate cancer without unnecessary treatment of clinically insignificant cancers.

Humans↗
PubMed2000

Advanced prostate cancer is associated with a decrease in serum luteinizing hormone.

OBJECTIVE: Depletion of serum LH by LHRH agonists is used as a therapeutic treatment in hormone-sensitive prostate cancer (PCa). However, little information on serum LH in different patient groups is available. METHODS: Patients with biopsy-proven PCa, men with BPH (biopsy-proven absence of PCa), two subgroups (serum PSA <4 ng/ml; PCa and BPH), and a PCa cohort before and after radical prostatectomy were analyzed for serum LH, testosterone (T), dihydrotestosterone (DHT), total and free PSA by immunological procedures. RESULTS: PCa patients with cancer volumes >10 cm(3), or with advanced Gleason scores, had significantly lower LH values than men in a cancer-free control group (PSA <4 ng/ml). Eight weeks after radical prostatectomy, LH levels had returned to the level of the control group (p<0.0001). These alterations were not accompanied by corresponding changes of serum androgens. Introduction of a PSA/LH ratio appeared to increase the differences between BPH and PCA groups ranked according to Gleason scores, versus PSA or LH alone. However, the calculation of ROC curves indicated that PSA/LH ratios may not improve the discrimination of malignant and benign forms of the disease, compared to presently used parameters. CONCLUSIONS: A significant reduction of circulating LH is observed in the most advanced forms of PCa. The effect does not come about by T- or DHT-mediated feedback inhibition. Since LH values after prostatectomy returned to practically the same levels as seen in the control group (BPH with <4 ng/ml PSA), it appears that the healthy prostate has no marked influence on serum LH while advanced PCa induces a decrease in serum LH.

Adult↗
PubMed1999

Early prostate-specific antigen relapse after radical retropubic prostatectomy: prediction on the basis of preoperative and postoperative tumor characteristics.

OBJECTIVES: This study was undertaken to distinguish between patients who will and will not benefit from a retropubic radical prostatectomy (RRP) for clinically localized prostatic carcinoma (PCa) on the basis of preoperative and postoperative tumor characteristics. METHODS: Data of 318 consecutive patients who underwent RRP for clinically localized PCa were reviewed. Preoperative characteristics used included clinical stage, findings on transrectal ultrasonography, prostate-specific antigen (PSA) values, Gleason grade, number of positive biopsies, number of biopsies containing any Gleason grade 4 and/or 5 cancer, and number of biopsies with predominant (>50% of cancerous tissue) Gleason grade 4 and/or 5 cancer. Postoperative characteristics included pathologic stage, Gleason grade, margin status, cancer volume, and volume of Gleason grade 4 and/or 5 cancer. The impact on biochemical relapse after RRP were calculated by Cox regression and CART (classification and regression tree) analysis to establish low, intermediate, and high risk of recurrence. RESULTS: Of patients who underwent RRP, 66% showed no evidence of relapse after a follow-up of 42 months. All preoperative and postoperative characteristics showed a significant association with biochemical relapse. Cox regression of preoperative characteristics showed the number of positive biopsies with predominant Gleason grade 4 and/or 5 cancer to be the most accurate predictor of failure (p < 0.0001), followed by the number of positive biopsies and PSA. CART analysis distinguished between four risk groups on the basis of the same characteristics as in the Cox regression. The low-risk group consisted of 232 patients (75.1%) and the high-risk group of 17 patients (5.5%); corresponding Kaplan-Meier curves showed a 2-year PSA-free survival rate of 97% for the low-risk group and 20% for the high-risk group. Cox regression of postoperative characteristics recognized the volume of Gleason grade 4 and/or 5 as the characteristic with the strongest association with biochemical failure. CART analysis distinguished between four risk groups, using the volume of high-grade cancer as the most influential characteristic. The corresponding Kaplan-Meier curves showed for the low-risk group (n = 79; 29.6%) a PSA-free survival rate of 96% after 42 months and for the high-risk group (n = 47; 17.6%) a 21% PSA-free survival rate after 42 months. CONCLUSION: For preoperative and postoperative estimation of biochemical recurrence after RRP, a quantitative analysis of high-grade cancer, expressed by the number of preoperative biopsy cores containing high-grade cancer and the volume of cancer, proved to be the best predictor of relapse. CART analysis might be useful in advising patients for their best therapy options. However, defined characteristics of risk groups should be evaluated with new prospective data before they are used routinely.

Adenocarcinoma↗
PubMed1999

Molecular heterogeneity of free PSA in sera of patients with benign and malignant prostate tumors.

OBJECTIVE: To analyze free prostate-specific antigen (f-PSA) in sera from patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH), and to detect possible differences in subtypes as potential diagnostic parameters. MATERIALS AND METHODS: PSA was purified from sera by an immunoaffinity procedure developed on the basis of oriented antibody immobilization, and subjected to size exclusion chromatography (SEC), Western blotting, and N-terminal amino acid sequencing. RESULTS: The novel procedure allowed the purification of PSA with high yield from sera containing PSA <10 ng/ml. SEC under nonreducing conditions as well as Western blots demonstrated the presence of several molecular forms of f-PSA. Three of the smaller polypeptides exhibited the N-terminal sequence of PSA while one represented the C-terminal fragment Lys(146)-Pro(237). Shortening of some polypeptides by the N-terminal amino acid Ile(1) suggestive of aminopeptidase action was also observed. No propeptide sequence could be detected, and none of the bands from patient sera reacted with antibodies raised against propeptide antigens. BPH sera expressed higher proportions of smaller PSA fragments per unit p33, and contained significant amounts of fragments <14,000 which appeared to be very low or absent from most PCa sera. CONCLUSIONS: f-PSA as obtained from BPH and PCa sera represents a heterogeneous fraction. The major component (p33) is not in the nicked form and does not contain proPSA. Diagnostic potential could arise from the quantitative differences of the smaller PSA derivatives seen between PCa and BPH sera.

Amino Acid Sequence↗
PubMed1999

Ultrasensitive detection of prostate specific antigen in the followup of 422 patients after radical prostatectomy.

PURPOSE: We validated our ultrasensitive prostate specific antigen (PSA) assay based on lyophilization and 4-fold concentration of patient sera with the clinical long-term followup and according to histopathological characteristics of 422 patients treated with radical retropubic prostatectomy for prostate cancer. MATERIALS AND METHODS: Each serum sample was divided into 2 aliquots for standard and 4-fold concentrated (ultrasensitive) detection. Samples were analyzed by the same unmodified DPC-Immulite PSA assay. Biochemical relapse was defined as an increase of at least 0.10 ng./ml. in native serum (equivalent to 0.025 ng./ml. in concentrated serum). Mean followup was 449 days (range 29 to 2,057). Kaplan-Meier analysis of standard and ultrasensitive detection results was done, and findings were correlated with pathological stage, Gleason grade, total cancer volume, Gleason grade 4 cancer volume and margin status. Significance of earlier detection in ultrasensitive versus standard detection was calculated with the log rank (Mantel-Cox) test with p <0.05 considered significant. RESULTS: Of 442 patients 88 (20.8%) experienced biochemical recurrence. Of this cohort 28 (31%) demonstrated early failure on the ultrasensitive assay which was later confirmed on the standard assay, 37 (42%) had failure simultaneously on both assays and 23 (26%) had failure on the ultrasensitive but remained disease-free on the standard assay. Average time for ultrasensitive assay detection of recurrence was 288 days (standard 555). Kaplan-Meier analysis revealed significant advantages in earlier detection of recurrence with the ultrasensitive assay, and close correlation with pathological stage, Gleason grade, margin status and Gleason grade 4 cancer volume. Time advantages of ultrasensitive versus standard detection were greater for advanced cancers (pT3a/b or greater, Gleason 3 + 4 or greater) than for small, low grade tumors. All patients who had positive results on the standard assay had a previous (28) or simultaneous (37) positive ultrasensitive result. With standard detection 25% of all relapses were evident within the first year of surgery and with ultrasensitive detection the percentage increased to 85.7%. On both assays 334 patients remained free of biochemical recurrence. CONCLUSIONS: Our ultrasensitive PSA assay is useful for early detection of biochemical relapse after radical retropubic prostatectomy. It not only provides the same accuracy as conventional PSA assays but also offers the advantage of detecting recurrence about 300 days earlier. Thus, long-term results of radical retropubic prostatectomy series can be calculated sooner. The clinical impact of this assay will be obvious once curative treatment options are available if applied at the earliest time of evident tumor recurrence.

Follow-Up Studies↗
PubMed1998

Interphase cytogenetic study of preoperative core biopsies for the prediction of early serum prostate specific antigen recurrence after radical prostatectomy of clinically localized prostate carcinoma.

BACKGROUND: Current clinical and pathologic methods are imprecise in predicting the extent of prostate carcinoma progression. This study was conducted to evaluate the role of interphase cytogenetics (ICG) with chromosome enumeration probes relative to the role of conventional pathologic characteristics in the preoperative prediction of postoperative tumor classification and recurrence of elevated serum concentrations of prostate specific antigen (PSA). METHODS: The authors performed ICG with enumeration probes for chromosomes 7, 17, and X on 6-microm sections of core biopsies from 75 patients with clinically localized adenocarcinoma of the prostate. Results were compared with pathologic findings (tumor classification, volume, and status of surgical margins) of the corresponding radical prostatectomy specimens and data on serum PSA measurements taken for 72 patients during a follow-up period of up to 42 months (mean, 19.8 months). In addition to ICG, biopsies were reviewed for primary, secondary, highest, and combined Gleason grades, number and bilaterality of positive biopsies, amount of carcinoma (percentage and core length of infiltration), amount of high grade carcinoma, and perineural invasion. RESULTS: Chromosome categories were unevenly distributed among pathologic tumor classification groups (P = 0.0008) and between groups with positive and negative surgical margins (P = 0.0116). Tumors with aneusomic chromosome numbers had larger volumes than those with eusomy and tetrasomy (P = 0.0022). Kaplan-Meier analysis demonstrated that PSA recurrences (> or = 0.4 ng/mL) were more frequent and observed earlier in patients with detected chromosomal aneusomies than in those with eusomic and tetrasomic chromosome numbers (P < 0.0001). Cox regression analysis indicated that ICG was the most valuable independent factor in predicting PSA recurrences. CONCLUSIONS: The detection of numeric chromosomal aberrations in preoperative core biopsies is an adverse prognostic sign. Grading based on the quantification of genetic changes might prove useful in the prognostic stratification of patients with clinically localized prostate carcinoma.

Adenocarcinoma↗
PubMed1998

[Development of tumor selection based on pathological stage in clinically localized prostate carcinoma].

Four hundred and eighty-eight radical retropubic prostatectomies (RRP) were performed on clinically localized prostate cancer at one institution within 5 years (1992-1996). These were then analyzed regarding the migration of pathological tumor stages towards more localized stages. Within the observation period, the annual rate of RRP increased by 81% from 69 to 125 cases. The authors noted a decline in the occurrence of advanced tumor stages (65.0% to 39.2%) and small cancers (< 0.5 cc: 7.2% to 1.6%) and an increase in pathological T2 tumors (30.4% to 55.2%). The rate of positive surgical margins declined from 34.7% to 12.8% (for all pathological stages). These data confirm trends which were observed in the USA with increasing detection and treatment of localized prostate cancer.

Biomarkers, Tumor↗
PubMed1998

[Plasma TGF-beta1 concentrations in patients with prostate carcinoma or benign prostatic hyperplasia].

Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotrophic growth factor in carcinogenesis and regulars multiple cell functions. We wanted to evaluate the diagnostic meaning of TGF-beta 1 plasma levels in patients with a biopsy proven prostate cancer. The TGF-beta 1 blood level was analysed in 394 patients. In 242 patients (group I) the blood was taken before any prostate manipulation and biopsy. The TGF-beta 1 plasma concentrations were almost similar in the group of patients with a prostate cancer (n = 157) and patients with a benign prostate hyperplasia (n = 85; 14,258 pg/ml versus 14,658 pg/ml, SD 10,516 pg/ml). In 152 patients the blood was taken 6-12 months after radical prostatectomy (group II). There was no significant difference between the patients with a PSA-progress and without PSA-progress after. Our results suggest that TGF-beta 1 plasma levels can not be used to distinguish between patients with prostate cancer and benign prostate hyperplasia.

Biomarkers, Tumor↗
PubMed1998

The value of the ratio of free-to-total prostate specific antigen for staging purposes in previously untreated prostate cancer.

PURPOSE: We analyzed the use of the ratio of free-to-total prostate specific antigen (PSA), also termed percentage of free PSA, for predicting tumor stage, volume and grade in patients with clinically localized prostate cancer. MATERIALS AND METHODS: A total of 515 consecutive patients underwent further prostate evaluation due to elevated PSA (greater than 4.0 ng./ml.) or abnormal digital rectal examination. Prostate cancer was diagnosed in 307 patients (59.6%), including 170 (55.4%) who underwent radical retropubic prostatectomy. Data on pathological stage, Gleason grade, and total and Gleason grade 4 cancer volume were available in all patients. In the remaining 208 men (40.4%) benign prostate hyperplasia was diagnosed. Total and free PSA was measured in preoperative serum. RESULTS: Total PSA was significantly higher (p <0.0001) in the 71 men with stage pT3 tumors than in the 91 with pT2 disease. Eight patients had stage pT4 tumors. Cancer volume correlated well with advancing pathological stage (p <0.0001) and total PSA (p <0.0001). The free-to-total PSA ratio was not significantly different (p = 0.93) in stages pT2 and pT3 tumors, and it did not correlate with total (p = 0.71) or pure Gleason grade 4 (p = 0.94) cancer volume. However, the ratio of free-to-total PSA tended to decrease (p = 0.07) in tumors of increasing Gleason grade. CONCLUSIONS: The ratio of free-to-total PSA does not help in the preoperative prediction of final tumor stage and volume. However, disease grading may alter the free-to-total PSA ratio.

Biomarkers, Tumor↗
PubMed1998

Incidence of positive surgical margins after biopsy-selected nerve-sparing radical prostatectomy.

OBJECTIVES: The selection criteria for a nerve-sparing radical prostatectomy (NSRP) are not thoroughly investigated and are based mainly on preoperative digital rectal examinations and intraoperative findings. At our institution NSRP is performed only on patients whose preoperative systematic sextant biopsy of the prostate showed only unilateral cancer. To prove the safety of these criteria, we analyzed the incidence of positive surgical margins and tumor progression rate in patients who were selected for an NSRP only by the result of the biopsy. METHODS: Preoperative systematic sextant biopsies revealed unilateral cancer in 69 preoperatively potent men of 289 consecutive prostatic cancer patients (23.9%); contralateral NSRP was performed on these 69 patients. The prostate specimens were investigated by using a 3-mm step-section technique to identify positive surgical margins. Tumor progression was defined as a prostate-specific antigen (PSA) level greater than 0.4 ng/mL in the native and greater than 0.025 ng/mL in the suprasensitive postoperative blood test. Mean follow-up was 15 months (range 6 to 24). RESULTS: In 69 patients who underwent NSRP, 11 positive margins (15.9%) were found. Only 3 patients (4.3%) had a positive margin on the nerve-sparing side. In 220 patients who underwent non-NSRP 59 positive margins (26.8%) were detected. PSA recurrence rate after 12 months was similar in patients with NSRP and non-NSRP. Analysis of systematic sextant biopsies gives safe selection criteria because in approximately 95% the surgical margin on the nerve-sparing side will be negative. CONCLUSIONS: Basing the indication for an NSRP on the results of preoperative systematic biopsies was safe according to margin status and postoperative PSA, when all patients with tumor in one of the three biopsy cores of each side of the prostate were excluded from an NS technique on that side. Such a strict approach will exclude approximately 30% of patients from NSRP unnecessarily because of tumor findings on a prostate side where the cancer is still organ-confined. Less strict criteria, including patients with only well-differentiated cancer and a maximum of one positive biopsy on the evaluated side, seem to be as safe as the described selection. However, data on these patients need further evaluation.

Aged↗