[Practice of early detection of prostate cancer : Descriptive survey in preparation for the PSAInForm study]. / Praxis der Früherkennung des Prostatakarzinoms : Deskriptive Erhebung im Vorfeld der PSAInForm-Studie.

BACKGROUND: The randomized controlled PSAInForm study aims to investigate the effects of a computer-based decision aid which informs men in the age group 55-69 years about advantages and disadvantages of PSA testing. In preparation for the study, the current PSA testing practice in the Münster district was assessed. MATERIALS AND METHODS: The frequencies of early detection examinations, medically indicated PSA tests, and prostate biopsies in the Münster district were determined, using aggregated data from the regional association of Statutory Health Insurance (SHI) Physicians in Westfalen-Lippe. With anonymized laboratory data, the frequency of PSA tests in general and urological practices, and their distribution among the accounting categories SHI, individual health services, and invoices for privately insured patients were investigated. RESULTS: In about half of more than 50,000 PSA tests, the accounting category could be determined; the rest could only be assigned to SHI or non-SHI services. The percentage of PSA tests that were performed due to reasons other than medically necessary SHI-reimbursed services was > 50% in each age group; it was highest in men younger than 55 years, and declined markedly with advanced age. More than half of the PSA tests that were likely due to opportunistic screening were performed outside the age group 55-69 years. CONCLUSIONS: The percentage of PSA tests that were not carried out as SHI services was > 80% in general practices, and 60% in urological practices. These percentages decreased markedly with advancing age. Most of the PSA tests were performed outside the age group which can be considered as the target group for an effective PSA screening according to the results of the European Randomized study of Screening for Prostate Cancer (ERSPC).

[Use of the S3 guidelines for early detection of prostate cancer in urological practices]. / Anwendung der S3-Leitlinie zur Prostatakrebsfrüherkennung in urologischen Praxen.

OBJECTIVES: The German S3 guideline on prostate cancer gives recommendations on early detection of prostate cancer. In this study we analyzed the adherence of urologists in private practice from the administrative district of Münster, Germany to this guideline. METHODS: Data were collected through a semistructured survey of 22 urologists based on the COREQ checklist (Consolidated criteria for reporting qualitative research) in four focus groups consisting of five or six urologists in private practice. We developed 23 questions relating to 12 recommendations of the paragraphs of the S3 guidelines dealing with early detection of prostate cancer and prostate biopsy. The recommendations of the guideline are subdivided in nine "strong", one "optional recommendation" and two "statements". The adherence to the guideline was investigated by using frequency and qualitative content analysis (Mayring) based on a mixed methods design. RESULTS: The urologists follow six of the nine "strong recommendations" of the guideline and deviate from three. Reasons for deviations from "strong recommendations" are the following: information about advantages and disadvantages of early detection for prostate cancer, recommendation of a prostate biopsy in case of PSA level ≥4 ng/ml, and indication for repeat biopsy. CONCLUSION: Most of the "strong recommendations" are followed by the interviewed urologists of the administrative district of Münster. Contextually relevant deviations from "strong recommendations" are justified, e. g., the only limited transferability of the PSA threshold of 4 ng/ml derived from population-based studies of asymptomatic men to men presenting in a urologist's office.

An electronic specimen collection protocol schema (eSCPS). Document architecture for specimen management and the exchange of specimen collection protocols between biobanking information systems.

BACKGROUND: The integrity of collection protocols in biobanking is essential for a high-quality sample preparation process. However, there is not currently a well-defined universal method for integrating collection protocols in the biobanking information system (BIMS). Therefore, an electronic schema of the collection protocol that is based on Extensible Markup Language (XML) is required to maintain the integrity and enable the exchange of collection protocols. MATERIALS AND METHODS: The development and implementation of an electronic specimen collection protocol schema (eSCPS) was performed at two institutions (Muenster and Cologne) in three stages. First, we analyzed the infrastructure that was already established at both the biorepository and the hospital information systems of these institutions and determined the requirements for the sufficient preparation of specimens and documentation. Second, we designed an eSCPS according to these requirements. Finally, a prospective study was conducted to implement and evaluate the novel schema in the current BIMS. RESULTS: We designed an eSCPS that provides all of the relevant information about collection protocols. Ten electronic collection protocols were generated using the supplementary Protocol Editor tool, and these protocols were successfully implemented in the existing BIMS. Moreover, an electronic list of collection protocols for the current studies being performed at each institution was included, new collection protocols were added, and the existing protocols were redesigned to be modifiable. The documentation time was significantly reduced after implementing the eSCPS (5 ± 2 min vs. 7 ± 3 min; p = 0.0002). CONCLUSION: The eSCPS improves the integrity and facilitates the exchange of specimen collection protocols in the existing open-source BIMS.

[DiaPat urine test for prostate cancer. Predictive value for results of transrectal ultrasound-guided prostate biopsies]. / DiaPat-Prostatakarzinom-Urintest. Vorhersagekraft für das Ergebnis transrektal-sonographisch gesteuerter Prostatabiopsien.

BACKGROUND: A novel urine test for early detection of prostate cancer (PCA), distributed and marketed by the company DiaPat, is advertised by the statement "correct analysis in 9 of 10 cases." PATIENTS AND METHODS: The test separates urinary polypeptides by means of capillary electrophoresis and characterizes the peptides in a time-of-flight mass spectrometer. The DiaPat test was performed on the urine of 18 men prior to multiple ultrasound-guided prostate biopsies. RESULTS: Sixteen of the 18 samples met the requirements for sample quality as established by the manufacturer. Eight of these 16 urine samples had been collected from patients in whom biopsies consecutively detected PCA; the remaining eight patients had benign biopsy results. Among the eight patients with detected PCA, the urine test yielded a low probability for PCA in three cases and a high probability in five. Within the group of eight patients with benign biopsy results, the urine test predicted a high probability for PCA in five men and a low probability in three. For the given PCA incidence of 50% within the investigated population, the DiaPat test correctly predicted biopsy results in one half of the population, whereas prediction in the remaining half was incorrect. CONCLUSION: Unless reliable validation of the DiaPat urine test for PCA is available, no clinical consequences should be drawn from the test results.

[Epidemiology of prostate cancer: recent results from the Epidemiological Cancer Register of the District of Münster (Germany)]. / Aktuelle Daten zur Epidemiologie des Prostatakarzinoms : Ergebnisse aus dem Regierungsbezirk Münster.

BACKGROUND: Prostate cancer is characterized by worldwide increasing incidence rates, improved survival, and decreasing mortality. We investigated the current situation in the Epidemiological Cancer Register of the District of Münster, Germany (which has approximately 1.25 million male inhabitants). MATERIALS AND METHODS: We calculated the incidence and mortality rates, stage distribution, and relative survival rates for prostate cancer between the years 2002 and 2004. RESULTS: The age-standardized incidence rate was 115/100,000 men per year, and the median age at diagnosis was 70 years. The tumour stage was T1/T2 in 69.6% of cases. The estimated relative survival after 5 years was 83.5% (95% confidence interval 81.4-85.4) and after 10 years was 73.3% (69.5-77.0). Survival was barely affected when the tumour was limited to the prostate (UICC I-II), whereas survival rates were markedly reduced when the tumour had spread or had infiltrated adjacent structures (UICC IV; relative 10-year survival rate 22.1%). CONCLUSIONS: The majority of patients with prostate cancer now have a favourable prognosis. Increased incidence rates must be interpreted in the context of widespread use of prostate-specific antigen testing.

Serum antibodies against prostasomal clusterin in prostate cancer patients.

OBJECTIVE: Clusterin is a ubiquitous secretory sulphated glycoprotein present in prostasomes. It is an anti-apoptotic mediator in prostate cancer and is among the most frequently occurring prostasomal proteins immunogenic in prostate cancer patients. The aim of the present study was to investigate the occurrence of anti-clusterin antibodies in the serum of patients with prostate cancer and whether there is a relationship between anti-clusterin antibody titres and other clinico-pathological variables. MATERIAL AND METHODS: Serum samples were collected from 391 consecutive patients with suspected prostate cancer (150 benign prostate and 241 prostate cancer). The patients' serum samples were used in an ELISA where microtitre wells were coated with purified clusterin from serum of a healthy volunteer. Flow cytometric studies of clusterin and prostasomes were performed. RESULTS: Flow cytometric analyses revealed the presence of clusterin on the surface of seminal prostasomes. Anti-clusterin ELISA titres in sera of patients did not differ significantly from those of a control group. A significant "inverse" correlation existed between anti-clusterin ELISA titres and lymph node metastases (p = 0.047), but only 11 out of 161 patients had metastases. These titres correlated significantly with total prostate (p = 0.021) and transitional zone (p = 0.015) volumes of the patients. CONCLUSIONS: The correlation between serum anti-clusterin antibody titres and other clinico-pathological variables was generally weak in prostate cancer patients, although clusterin has been assigned an important role in tumourigenesis and progression of prostate cancer. However, the anti-clusterin antibody titre appeared to be related to prostate volume, correlating to both transitional zone volume and total volume of the prostate.

Blockage of urine by intravesical ejaculate in cynomolgus monkeys.

BACKGROUND: The present communication reports intravesical semen coagulation and formation of a larger precipitate in two Cynomolgus monkeys. METHODS: Ultrasound of the urinary bladder and light microscopy of intravesical coagulates. RESULTS: These monkeys suffered from complete blockage of urine output and surgery was required to remove the sperm mass. Microscopic examination of the urine revealed millions of sperm as a cause of the mass and the blockage of urine output. CONCLUSIONS: Retrograde ejaculation of sperm may cause coagulation of ejaculates in the bladder of the cynomolgus monkey Macaca fascicularis. However, involvement of sperm mass in blockage of urine passage has not been described in this species.

Implementation of a map in radical prostatectomy specimen allows visual estimation of tumor volume.

INTRODUCTION: Tumor volume is one of the best documented prognostic factors for prostate cancer. There are several methods to gain this important parameter but unfortunately most of the clinicians in the world do not get this information in their routine practice from the pathologist. We developed a standardized method to handle radical prostatectomy specimens including a special form of mapping in order to document relevant morphological data. The aim of this study was to investigate if our model of mapping prostate cancer, which we use in routine practice, may serve for visual estimation of tumor volume. METHODS: We estimated the tumor volume of prostate cancer by visual estimation of 350 maps of radical prostatectomy specimens and correlated these data with established prognostic parameters and clinical outcome. RESULTS: Significant correlations between tumor volumes, as obtained from our mapping, and known prognostic parameters such as preoperative serum levels of prostatic specific antigen, loss of differentiation, histological grade, lymph node metastasis, and margins were found. In a multivariate analysis, only Gleason score and tumor stage were shown to be independent prognostic parameters. DISCUSSION: We demonstrate that mapping of prostate cancer is more than a simple method of documentation but may serve as a method for visual estimation of tumor volume of prostate cancer after radical prostatectomy. This method can further be used for a visual documentation of the tumor stage independent of changes in the TNM classification. The method is inexpensive and practicable and can therefore be applied in routine surgical pathology.

[Mapping of a deletion interval on 8p21-22 in prostate cancer by gene dosage PCR]. / Mapping eines Deletionsintervalls auf 8p21-22 beim Prostatakarzinom mittels Gendosis-PCR.

Various microsatellite and CGH studies in prostate cancer identify deletions on the short arm of chromosome 8 especially at band 8p21-22 searching for unknown putative tumor suppressor genes. By means of microsatellite markers several candidate genes were detected which may play different roles in early prostate cancer progression. We established a quantitative gene dosage PCR based on the real time PCR method serving the purpose of genomic fine mapping. Therefore we used 10 Assays-on Demand (ABI) for the detection of deletions located between and nearby the microsatellite markers D8S258 and NEFL spanning a genomic region of approximate 7 mbp. Comparative immunohistochemical analysis from tissue micro arrays (TMA) of 1122 independent cases followed. We were able to detect three clearly separated deletion intervals on 8p21-22. One on LZTS1, second on NEFL and third a deletion hot spot on LOXL2, which was affected in 72% of all investigated cases. Our comparative immunohistochemical TMA based studies demonstrate that LOXL2 is nearly lost in most prostate cancer tissues. LOXL2 catalyze the crosslinking of collagen and elastin in the extracellular matrix and it has been assumed that it is involved in tumor suppression and cell adhesion. LOXL2 is frequently expressed in proliferating tissues and shows a high expression in benign prostate tissue too. In prostate cancer the expression is positive correlated with the MIB1-score.

Frequent detection and immunophenotyping of prostate-derived cell clusters in the peripheral blood of prostate cancer patients.

BACKGROUND: Recent scientific studies have failed to determine parameters for the assessment of prostate cancer aggressiveness. The present study deals with the detection of blood-borne cancer cells based on polymerase chain reaction (PCR) and cell enrichment methods. The contradictory results reported in the literature have called into question the clinical usefulness of this diagnostic method in the preoperative staging of clinically localized prostate cancer. METHODS: We established a combined method of density gradient centrifugation and immunomagnetic separation using epithelium-specific antibodies, i.e. cytokeratins, to isolate prostate-derived circulating cells from the peripheral blood of patients with prostate cancer. Isolated cells were characterized by DNA staining and immunocytochemistry using antibodies for the detection of prostate-specific antigen (PSA), proliferation-associated proteins (MIB-1, H1 and H3) and apoptosis-associated proteins (M30, c-FasR). RESULTS: We applied these methods to 68 prostate cancer patients and were able to isolate cell clusters in 98%. Immunophenotypic and morphological characterization of PSA-positive prostate-derived cell clusters found in the peripheral blood of prostate cancer patients showed two main populations: 1) in 35% of the investigated prostate cancer patients we detected rounded cell aggregates of probable cancer cells expressing proliferation-associated proteins and lacking apoptosis-associated protein expression; 2) in all cases there was a high frequency of circulating dysmorphic cell clusters positive for apoptosis-associated protein expression. CONCLUSION: Our results demonstrate the existence of at least two different types of blood-borne prostate-derived circulating cell clusters. Of these, only the less frequent, round, small cell clusters harbor features that are probably necessary for the cells to survive for metastatic spread.

The impact of intraoperative manipulation of the prostate on total and free prostate-specific antigen.

OBJECTIVES: It is well documented that mechanical manipulation of the prostate can elevate total PSA (t-PSA) levels in serum. However, less is known about its effects on free PSA (f-PSA) and the free-to-total PSA ratio (f/t-PSA). We therefore examined the impact of prostate manipulation on t-PSA and f-PSA during surgical procedures involving the prostate. METHODS: Intraoperative blood samples for t-PSA and f-PSA measurement (Hybritech) were collected every 15 min during 14 radical retropubic prostatectomies (RRP) and 10 radical cystoprostatectomies (RCP). RESULTS: Prostatic manipulation induced significant elevations in t-PSA and f-PSA during RRP and RCP. Postmanipulatory peaks were markedly higher for f-PSA than for t-PSA. The mean maximum f-PSA levels showed a 4.3- (RRP) and 7.9-fold (RCP) increase, followed by a rapid decline after prostate removal. t-PSA increased 1.2- (RRP) and 1.3-fold (RCP), and declined more slowly. Postmanipulatory f/t-PSA ratios also increased significantly, reaching mean elevations of +0.29 and +0.28 over preoperative ratios during RRP and RCP, respectively. CONCLUSIONS: Prostate manipulation can induce transient increases in t-PSA, f-PSA and f/t-PSA in benign and malignant prostates. The extent of these alterations and their course over time must be taken into account when postmanipulatory changes in PSA forms are investigated. Timing of postmanipulatory venipunctures and the molar response ratio of t-PSA assays used (equimolar versus nonequimolar) seem to have substantial impact on the results of such studies.

Intraoperative washing of long-stored packed red blood cells by using an autotransfusion device prevents hyperkalemia.

IMPLICATIONS: Long-stored packed red blood cells (PRBCs) have a large potassium load. In patients with end-stage renal failure, the transfusion of such PRBCs may cause a critical increase in plasma potassium levels. Washing PRBCs with an autotransfusion device allows for a marked decrease in potassium load, thus preventing hyperkalemia.

Late recurrence of adenoid cystic carcinoma of the prostate.

A 44-year-old patient underwent radical prostatectomy and adjuvant radiotherapy for adenoid cystic carcinoma of the prostate. After 7 years and 3 months he recurred locally and was treated with external beam irradiation. The current follow up comprises 9 years and 5 months at which the patient is asymptomatic with stable disease. Lymph node or distant metastases did never occur and the prostate specific antigen level was always within the normal range.

Flow cytometric DNA and phenotype analysis in pathology. A meeting report of a symposium at the annual conference of the German Society of Pathology, Kiel, Germany, 6-9 June 2000.

This meeting report summarizes the presentations of three different groups that are active in the field of flow cytometry (FCM) in relation to diagnosing and classification of proliferative disorders. The report starts with the contribution from Regensburg about the developments in DNA FCM, the progression to dual parameter determinations, and combination of immunophenotyping in combination with DNA. In the second part, the use of FCM for the detection of isolated tumor cells in the peripheral blood from patients with prostate or breast cancer is discussed in a contribution from Münster. In the third part, from Heerlen, the use of multi-parameter FCM on formalin-fixed paraffin-embedded tissues from solid tumors is discussed as a new development and application in routine surgical pathology.

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.