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Objectives: To examine, in a prospective, randomized study, the effect of different anesthetic techniques versus no anesthesia in a 10-core prostate biopsy. Reports thus far have shown a high variability in assessing the pain intensity of prostate biopsies and the effectiveness of anesthesia., Methods: Ultrasound-guided 10-core prostate biopsy was performed. Patients were prospectively randomized into four groups: no local anesthesia (group 1); anesthetic block of the prostatic plexus (group 2); local anesthesia onto the capsula of the apex (group 3); and a combination of the anesthesia used for groups 2 and 3 (group 4). The degree of pain was recorded using the visual analog scale/numeric analog scale (VAS/NAS) score., Results: The study included 187 patients. Results were assessed in 170 patients: 44 in group 1, 44 in group 2, 40 in group 3, and 42 in group 4. In group 1 (no anesthesia), 2 (4.5%) of 44 patients had no pain during biopsy (VAS/NAS = 0); the pain was mild (VAS/NAS of 1 to 4) in 38 (86.4%), moderate (VAS/NAS of 4 to 7) in 3 (6.8%), and severe (VAS/NAS of greater than 7) in 1 (2.3%) of 44 patients. The mean pain scores were 2.33 in group 1, 1.68 in group 2 (P = 0.05), 1.07 in group 3 (P <0.001), and 1.23 in group 4 (P <0.001). Pain caused by the local anesthesia itself was 0 in group 1, 1.52 in group 2 (P = 0.001), 1.05 in group 3 (P = 0.001), and 1.79 in group 4 (P = 0.001)., Conclusions: Local anesthesia significantly reduces pain. An injection onto the capsule at the apex was the most effective technique. It is technically easier to perform than an anesthetic block of the prostatic plexus and can be recommended.

The further course of prostate cancer (PC) after radical prostatectomy (RPX) is decisively influenced by the local tumor stage. Although it is now possible to assess the risk of local recurrence from the histopathology, precise predictions cannot be made. A more accurate evaluation would be desirable, mainly for early planning of adjuvant therapy. We assessed the detection of telomerase activity using the Telomeric Repeat Amplification Protocol in surgical margins compared to RT-PCR-supported prostate-specific antigen (PSA) mRNA detection and conventional histopathological examination. We examined 95 patients with local PC during RPX and 16 patients with muscle-invasive transitional bladder cancer who underwent radical cystectomy. After RPX or RCX biopsies were obtained from 4 or 3 defined areas of the prostatic fossa and processed by TRAP assay for telomerase activity and by RT-PCR for PSA using a standard protocol. Five of 48 patients (10.4%) with organ-confined prostate cancer (pT2) and 7 of 47 patients (14.9%) with locally advanced PC (>pT2) had positive detection of telomerase activity in at least one positive specimen. In contrast to RT-PCR for PSA mRNA and histological findings for organ-confined and locally advanced disease, detection of telomerase activity yielded no statistically significant correlation to clinical parameters. Only PC-patients with positive histopathological margins had a positive correlation between detection of telomerase activity and high Gleason scores (r=0.65, p=0.022). Based on the results obtained and the current state of knowledge, measurement of telomerase activity must be considered less sensitive than RT-PCR for PSA mRNA in surgical margins, although tumor specificity should theoretically be higher. It is not even sure at the present time whether a combination of both methods offers any recognizable advantage over PSA mRNA detection alone. The value of the results obtained in this study will have to be assessed in a further follow-up to determine whether patients with positive molecular detection have an increased risk of local recurrence.

Epigenetic DNA alterations such as promoter hypermethylation of glutathione S-transferase P1 (GSTP1) in prostatic adenocarcinoma frequently constitute tumour biomarkers. Neoplastic transformation was identified in washings of prostate biopsies by GSTP1 promoter hypermethylation, using methylation-specific PCR (MSP). Twenty-six patients undergoing sextant transrectal prostate biopsies for clinically suspected prostate cancer were enrolled. All ten patients diagnosed with adenocarcinoma (100%) and four of six patients with prostatic intraepithelial neoplasia (67%), but none of ten patients with benign hyperplasia (0%), exhibited GSTP1 promoter hypermethylation in at least one out of six biopsy washings. Since this approach is transferable to various cancer entities, a sensitive and specific DNA-based analysis of biopsy material seems generally feasible without impeding routine histopathological examination., (Copyright 2002 John Wiley & Sons, Ltd.)

Objectives: To report our initial experience gained in establishing real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection of prostate-specific antigen (PSA) mRNA using the quantitative online PCR system LightCycler. Many studies have thus far failed to provide the desired proof that the detection of circulating PSA-expressing tumor cells with RT-PCR in the blood samples of patients with prostate cancer (PCa) is a highly sensitive prognostic and course marker. One of the possible reasons is the lack of reliable quantification methods., Methods: Blood samples before and after surgery were obtained from 87 patients who underwent radical prostatectomy for locally confined PCa and 27 patients who underwent transurethral resection of the prostate for benign prostatic hyperplasia. Eight days postoperatively, additional blood samples were obtained from the patients with PCa. Quantitative no-nested RT-PCR for PSA mRNA (291 bp) was performed using the LightCycler system applying the SYBR Green protocol. The number of circulating LNCaP tumor cell-equivalents per sample was estimated from the mean amplification value measured in a given number of LNCaP cells., Results: PSA mRNA was detected preoperatively in 19 patients with Stage pT2 tumor (40%) and in 28 patients with tumor greater than Stage pT2 (72%), but in only 2 patients with benign prostatic hyperplasia (8%; analysis of variance, P <0.001). Significant quantitative differences were observed among Stage pT2 disease (1034 LNCaP tumor cell-equivalents/mL), greater than Stage pT2 disease (7830 cells/mL), and benign prostatic hyperplasia (58 cells/mL; analysis of variance for all groups, P <0.001). The correlation between the detection of PSA expression by RT-PCR and the Gleason score and serum PSA value was statistically significant., Conclusions: Our results show that the initial experience with the LightCycler system for PSA-assisted detection of circulating PSA mRNA in PCa by RT-PCR may be a promising preoperative prognostic marker for organ-confined or locally advanced PCa. Long-term follow-up of these patients with PCa must demonstrate the clinical value of molecular diagnostics with quantitative RT-PCR systems.

Background: The further course of prostate cancer (PC) after radical prostatectomy (RPX) is decisively influenced by the local tumor stage. Although it is thus far possible to assess the risk of local recurrence from the pathohistology, precise predictions cannot be made. A more precise evaluation would be desirable, mainly for early planning of adjuvant therapy. Other authors have shown that telomerase activity may be a marker for malignant potential. We assessed the detection of telomerase activity using the telomeric repeat amplification protocol (TRAP) in surgical margins compared to conventional histopathological examination., Methods: Ninety-two patients with local PC who underwent RPX were examined. After RPX biopsies were obtained from four defined areas of the prostatic fossa and processed by TRAP assay for telomerase activity using a standard protocol., Results: In 5 of 48 patients (10.4%) with organ-confined prostate carcinoma (pT2) telomerase activity could be detected. Seven of 47 patients (14.9%) with locally advanced PC (> pT2) had at least one positive specimen., Conclusions: The results obtained in our study indicate that detection of telomerase activity by TRAP assay may be a suitable parameter for molecular staging of surgical margins, because of the high tumor-specificity. Further follow-up must clarify whether patients with positive molecular detection have an increased risk of local recurrence., (Copyright 2001 Wiley-Liss, Inc.)

Objectives: Promoter hypermethylation of the glutathione-S-transferase P1 (GSTP1) gene is a specific feature of prostate cancer. This epigenetic DNA alteration served as the target for molecular detection of prostate cancer cells in urine sediments after prostatic massage., Methods: Bisulfite treatment followed by methylation-specific polymerase chain reaction was used to detect GSTP1 promoter hypermethylation in DNA isolated from urine sediments obtained after prostatic massage of men with and without prostate cancer., Results: GSTP1 promoter hypermethylation was demonstrated in the sediments of 1 (2%) of 45 patients diagnosed with benign prostatic hyperplasia, 2 (29%) of 7 patients with prostatic intraepithelial neoplasia, 15 (68%) of 22 patients with early, intracapsular cancer, and 14 (78%) of 18 patients with locally advanced or systemic prostate cancer, resulting in a specificity of 98% and an overall sensitivity of 73% for the detection of prostate cancer., Conclusions: Urinalysis for GSTP1 promoter hypermethylation constitutes a sensitive and highly specific DNA-based marker for molecular detection of prostate cancer, including early stages.

Background: Methylation-specific polymerase chain reaction (MSP) targeting promoter hypermethylation of the glutathione S transferase P1 gene (GSTP1), as the most frequent DNA alteration in prostatic carcinoma, was used for the molecular detection of cell-bound and cell-free prostate tumor DNA in various human bodily fluids., Materials and Methods: We investigated GSTP1 promoter hypermethylation in DNA isolated from plasma, serum, nucleated blood cells, ejaculates, urines after prostate massage, and prostate tissue from 33 patients with prostate cancer and 26 control patients with benign prostatic hyperplasia (BPH). Using a viral DNA extraction kit specifically recommended for DNA isolation from urine samples, GSTP1 promoter hypermethylation in urine sediments after prostatic massage was investigated in a cohort of 29 patients with prostate cancer and 40 controls with BPH. Fluorescently labeled MSP products were analyzed on an automated gene sequencer., Results: GSTP1 promoter hypermethylation was found in 90% of tumors (18 of 20), 72% of plasma or serum samples (23 of 32), 50% of ejaculates (4 of 8), and between 36% (4 of 11; normal DNA isolation kit) and 76% (22 of 29; viral kit) of exprimated urines from patients with prostate cancer. Also, MSP identified circulating tumor cells in 30% (10 out of 33) of prostate cancer patients. Except for one urine sample, GSTP1 promoter hypermethylation was not found in tissue and body fluids from patients with BPH., Conclusion: GSTP1 promoter methylation analysis provides a highly specific tool for DNA-based diagnosis of prostate cancer in body fluids.

There are few options for treating hormone-refractory prostate cancer (PC). Various studies indicate that luteinizing hormone-releasing hormone (LHRH) agonists may have a direct inhibitory effect on prostate tumors mediated by specific LHRH receptors. One study evaluated LHRH receptors in hormone-dependent PC tissue, but no data have thus far been obtained on the presence of LHRH receptors in benign prostatic hyperplasia (BPH) and especially hormone-refractory PC in patients. Thus, it is not yet clear whether LHRH receptors indicate tumor-related differentiation or even hormone-refractory dedifferentiation or are likewise associated with BPH. The aim of this study was to determine the rate of LHRH receptor mRNA expression in BPH and in primary, potentially androgen-dependent and in hormone-refractory PC with clinical progression. Multiplex reverse transcription-PCR was used to simultaneously detect the expression of mRNA for LHRH receptors and beta-actin in 48 patients with BPH, 14 with a primary, possibly hormone-dependent, prostate carcinoma (PPC), and 18 with a hormone-refractory prostate carcinoma (HRPC). Sixteen of 18 samples with HRPC showed intact RNA and expressed mRNA for LHRH receptors (100%). However, the RNA-intact PPC and BPH showed significantly lower expression of mRNA for LHRH receptors (46.2 and 55.3%, respectively; variance analysis: P = 0.0017). The significantly higher expression of mRNA for LHRH receptors in HRPC indicates that therapeutic concepts should be developed that target this site of action. In addition to possible direct effects of LHRH agonists or antagonists demonstrated previously in vitro, it seems useful to apply targeted cytotoxic LHRH analogues or monoclonal antibodies.

Objectives: To examine the application of reverse transcriptase-polymerase chain reaction (RT-PCR) to assist in prostate-specific antigen (PSA) detection in the surgical margins after radical prostatectomy (RP). The risk of local recurrence increases considerably in the presence of extracapsular tumor growth and/or positive surgical margins at RP. Although this makes it possible to identify patients with an increased risk of local recurrence, precise predictions cannot be made. A more precise assessment is desirable mainly for early planning of adjuvant therapy., Methods: Ninety-five patients with clinically organ-confined prostate cancer (CaP) underwent RP. After removing the gland, biopsies were obtained from four defined areas of the prostatic fossa and processed for RT-PCR for PSA detection. Sixteen patients with muscle-invasive bladder carcinoma who underwent radical cystoprostatectomy served as controls., Results: Thirty-two of 95 patients with CaP (35%) had at least one positive molecular margin indicating an expression for PSA; 19 of 48 (39%) of these had an organ-confined tumor stage according to conventional histology and 13 of 47 (28%) had tumor growth beyond the prostate. A statistically significant correlation between the frequency of positive molecular margins and clinical data was only observed in the group with disease greater than Stage pT2. All controls had negative molecular margins (P = 0.012)., Conclusions: On the basis of the results obtained, molecular diagnostic RT-PCR for PSA detection in the surgical margins after RP seems to be an interesting supplementary tool for monitoring the course and establishing the prognosis. Long-term follow-up of these patients is needed to demonstrate the clinical value of molecular diagnostics of surgical margins during RP.

Background: The quality of well-being scale (QWB) and the Medical Outcome Study 36-item short form (SF-36) are alternative methods for measuring general health outcomes. Few studies compare these approaches against one another and no studies have compared German language versions., Method: A German language version of the self-administered quality of well-being scale (QWB-SA) was developed using forward and back translation methods. The German QWB-SA and a German language version of the SF-36 were administered to clinical population groups with current diagnoses of prostate cancer, benign hyperplasia of the prostate, colon cancer, and rectal cancer. Data were obtained from four German clinics. In addition to the quality of life measures, data on cancer stage and disease state were obtained., Results: The QWB-SA and SF-36 were highly correlated. The QWB-SA was systematically related to disease state. Those with no symptomatic evidence had the highest scores followed by those who were stable with no metastatic disease and those with metastatic progression. Similar patterns were found for most SF-36 scales although the SF-36 failed to discriminate between those with no evidence of disease and those with stable disease without metastasis., Conclusions: Both the QWB-SA and SF-36 perform as expected using German language translations. Although both measures differentiate patients with metastasis from those without symptoms, the QWB-SA better differentiated those with no evidence of disease from those with stable disease without metastasis.

Promoter hypermethylation of the glutathione S-transferase P1 gene (GSTP1) is the most frequent DNA alteration in prostatic carcinoma. Because this epigenetic DNA alteration can be reliably detected by methylation-specific PCR (MSP), we applied this new technique for molecular detection of prostate cancer in various human bodily fluids. We investigated GSTP1 promoter hypermethylation in DNA isolated from plasma, serum, ejaculate, and urine after prostate massage and from prostate carcinoma tissues from 33 patients with prostate cancer and 26 control patients with benign prostatic hyperplasia (BPH). Fluorescently labeled MSP products were analyzed on an automated gene sequencer. Whereas GSTP1 promoter hypermethylation was not detectable by MSP in prostate tissue and bodily fluids from patients with BPH, we found it in 94% of tumors (16 of 17), 72% of plasma or serum samples (23 of 32), 50% of ejaculate (4 of 8) and 36% of urine (4 of 11) from patients with prostate cancer. Additionally, MSP identified circulating tumor cells in 30% (10 of 33) of prostate cancer patients. Analysis of GSTP1 promoter hypermethylation by MSP thus provides a specific tool for molecular diagnosis of prostate cancer in bodily fluids.

Objectives: The aim of this study was to evaluate whether pelvic lymph node metastases in patients with neoplasms of the bladder or prostate can be detected applying positron emission tomography with 2-[(18)F]-2-deoxy-D-glucose (FDG-PET)., Methods: Eight patients with bladder cancer and 17 patients with prostate cancer were examined with FDG-PET before pelvic lymph node dissection. Results of PET were then compared to histology of pelvic lymph nodes obtained at surgery., Results: Lymph node metastases were detected by histopathological examination in 3 patients with bladder cancer and in 6 patients with prostate cancer. At the sites with histologically proven metastases, increased FDG uptake suspicious of metastatic disease was found in 2/3 and 4/6 patients, respectively. The smallest detected metastasis was a micrometastasis with a diameter of 0.9 cm. In 3 additional patients who all had histopathologically proven micrometastases (