Hans-Peter Schmid

Five meters of H2O: The pressure at the urinary bladder neck during human ejaculation

There are no data in the literature on pressure changes in the prostatic urethra during ejaculation. In healthy men, it has always been postulated that there must be a pressure gradient in order to prevent retrograde ejaculation, but scientific proof for that is pending.

Semi-Quantitative Immunochromatographic Test for Prostate Specific Antigen in Whole Blood: Tossing the Coin to Predict Prostate Cancer?

OBJECTIVESnA strip test for the semi-quantitative determination of prostate specific antigen (PSA) based on whole blood was evaluated by the Working Group on Laboratory Diagnostics of the German Urological Association.nnnMETHODSnIn 301 men (156 volunteers and 145 referred patients, mean ages 57 years and 64 years) handling and capability of the strip test to predict PSA serum concentrations (Access Hybritech, Beckman Coulter, Inc., Fullerton, CA, USA) relative to a cutoff of 4 micro g/l were investigated. For patients, the strip test was performed by investigators, volunteers accomplished it according to leaflet instructions. Each test result was interpreted by both, the patient/volunteer and an investigator.nnnRESULTSn24% of the volunteers required assistance with test performance. The overall agreement between Access PSA (range 0.1-29.7) and strip test was 76% (read by participants) and 79% (read by investigators). Within the PSA ranges 0.1-3, 3.1-5 and 5.1-10, participants yielded agreement rates of 89%, 40% and 56%, respectively. Studying the 2.1-10 PSA range most relevant for prostate cancer screening, agreement rate (53%), sensitivity (50%) and specificity (67%) were barely superior to random chance. Volunteers alone (PSA range 0.1-11.3 micro g/l) yielded a specificity of 92%, however, all PSA values above the cutoff (n=8) went unrecognized and all positive strip tests (n=12) were incorrect (sensitivity 0%, positive predictive value 0%).nnnCONCLUSIONSnTest handling and interpretation was difficult. The rate of false strip test results is disappointing even for PSA ranges remote from the cutoff. In its present form the strip test fails to meet the clinical requirements and its launch to the market was therefore discontinued.

Clinical observations on the doubling time of prostate cancer

The serum marker prostate-specific antigen (PSA) has been shown to be proportional to the volume of prostate cancer (Yang polyclonal assay). Therefore, changes in PSA with time in untreated patients should reflect tumor growth rate and the shape of the growth curve. Forty-three patients with untreated prostate cancer had serial PSA measurements over an average time span of 30 months. The increase of PSA was exponential (log-linear) throughout the measured interval. Doubling times were faster in patients with higher stages and grades. Twenty of 28 cancers thought to be clinically organ confined doubled at rates exceeding 4 years. Tumor doubling times were overestimated in patients with large volume benign prostatic hyperplasia since hyperplasia increases serum PSA, albeit 12 times less than cancer. We conclude that prostate cancer has a constant (log-linear) growth rate which is very slow. This slow doubling time has substantial consequences for therapeutic decisions and for screening programs.

Bicycle riding has no important impact on total and free prostate-specific antigen serum levels in older men

OBJECTIVESnTo investigate whether bicycle riding significantly alters total prostate-specific antigen (tPSA), free PSA (fPSA), and percent free PSA (%fPSA) serum concentrations in potential candidates for prostate cancer screening.nnnMETHODSnThirty-three men, ranging in age from 50 to 74 years (mean 61 +/- 8), rode a 13-mile bicycle course. Blood samples for PSA analysis were drawn immediately before and 1 hour after cycling for 90 minutes. The precycling and postcycling tPSA, fPSA, and %fPSA values were compared using the Wilcoxon matched-pairs test, with P = 0.01 set as the significance level.nnnRESULTSnChanges between precycling and postcycling values for tPSA (P = 0.517), fPSA (P = 0.048), and %fPSA (P = 0.166) were not statistically significant.nnnCONCLUSIONSnPhysical activity combined with perineal pressure as induced by a 13-mile bicycle tour has no diagnostic impact on PSA values.

Prostate Specific Antigen Doubling Time as Auxiliary End Point in Hormone Refractory Prostatic Carcinoma

OBJECTIVEnIn hormone refractory prostatic carcinoma (HRPCa), the majority of patients have bone metastases only, which are by definition non-measurable. This makes objective evaluation of chemotherapeutic agents difficult. Prostate specific antigen (PSA) as a dynamic model was analyzed as potential auxiliary end point in HRPCa.nnnMETHODSnIn the framework of a master protocol, the Swiss Group for Clinical Cancer Research (SAKK) is evaluating cytotoxic drugs in HRPCa since 1991. These prospective phase II trials include uniform requirements with regard to response, toxicity and quality of life. From the entire pool of patients, 40 with bidimensionally measurable metastases (lymph nodes, visceral organs) could be identified. PSA doubling time was calculated in patients with a rising PSA during therapy.nnnRESULTSnObjective best response to any given chemotherapeutic agent was: partial remission (PR) in six patients (15%), stable disease (SD) in 13 (32%) and progressive disease (PD) in 21 (53%). PSA remained stable or decreased in four of six patients with PR (67%), seven of 13 with SD (54%) but only in four of 21 with PD (19%) (Cochran-Armitage test for trend; p=0.015). The median PSA doubling time for patients with a rising PSA was 238 days in PR and 224 days in SD, compared to 113 days in PD (Wilcoxon test; p=0.002).nnnCONCLUSIONSnPSA doubling time is a potential auxiliary end point in the evaluation of cytotoxic drugs in HRPCa. Thus, also patients with non-measurable (bone) metastases could be included in analysis of response.

Prostate Biopsy in Central Europe: Results of a Survey of Indication, Patient Preparation and Biopsy Technique

Objective: We surveyed urologists in Austria, Germany and Switzerland regarding their standard approach to prostate biopsy. Methods: Participants of Austrian and German urological meetings were asked to fill out a survey form; additionally, this was mailed to all Swiss urologists. Results: 304 surveys are available for analysis. 97% of participants perform a biopsy if digital rectal examination is abnormal. 63% use 4 ng/ml PSA (prostate-specific antigen) as cut-off. Age-related reference ranges are used by 54%, free PSA by 57%. 22% use PSA density, 55% PSA velocity. Overall 61% require a written consent, with 85, 86 and 25% in Austria, Germany and Switzerland. 96% of the urologists prescribe a quinolone antibiotic with a wide range regarding the start and end of drug therapy. 77% offer some kind of anaesthesia. Periprostatic injection of a local anaesthetic drug is used by 36%, lidocaine gel by 27%. 91% perform the biopsies transrectally under ultrasound guidance. Digitally guided biopsies are used by 11%. Only 3 participants perform perineal biopsies. The mean number of cores per biopsy session is 9.2, the maximum number of cores is 15.3 as a mean. Participants will stop performing any further biopsies if the patient already had a mean of 3.5 biopsy sessions. Conclusions: The majority of urologists in Central Europe prescribe a quinolone antibiotic and recommend some type of analgesia. The majority has abandoned the sextant technique and increases the number of cores in the case of rebiopsy. Biopsies are stopped after a mean of 3.5 sessions.

Combining Free and Total Prostate Specific Antigen Assays from Different Manufacturers: The Pitfalls

OBJECTIVESnWe investigated the impact of interchanging free prostate specific antigen (f-PSA) concentrations from 10 different assays over a reference total PSA (t-PSA) on predicting prostate histology with free-to-total PSA ratios (f/t-PSA).nnnMETHODSnArchival sera from 80 t-PSA- and age-matched pairs of histologically confirmed prostate cancer (PCA) and benign prostatic hyperplasia (BPH) patients with t-PSA levels between 2 and 25 microg/l were investigated. Serum aliquots were analyzed for t- and f-PSA using a reference method (Access, Beckmann-Coulter Hybritech) and 10 commercially available f-PSA assays. Passing Bablok and linear regression were performed to investigate the interassay agreement between f-PSA assays. To compare diagnostic performance, ROC curves for PCA detection were calculated for the 10 f/t-PSA combinations using the reference t-PSA as denominator. Sensitivities, specificities and f/t-PSA cut-offs were calculated for varying points of the ROC curve.nnnRESULTSnDespite good correlation of all 10 f-PSA assays with the reference method 4 showed significantly lower mean f-PSA levels. For f/t-PSA as a predictor of prostate histology, areas under the ROC curve (AUC) varied between 0.65 and 0.71 and, if compared to the reference method (AUC=0.70), were significantly lower in three cases. Ensuring 80% specificity, sensitivities ranged between 34% and 54% (reference method: 53%) and f/t-PSA cutpoints differed considerably depending on the f-PSA assay used (range: 0.15-0.24; reference: 0.15). Similar variations were noted at 95% specificity and 80% and 95% sensitivity.nnnCONCLUSIONSnArbitrary combinations of f- and t-PSA assays should not be used to calculate f/t-PSA ratios unless adequate studies have validated the diagnostic performance and cut-offs of that particular assay choice.

Pure primary choriocarcinoma of the urinary bladder with long-term survival

Choriocarcinoma was diagnosed in a 77-year-old woman with an acute massive, painless hematuria. One year after anterior pelvic exenteration and ileal conduit, the beta-human chorionic gonadotropin level increased to 934 mIU/mL without any sign of tumor progression. After six courses of chemotherapy (vincristine, actinomycin, and cyclophosphamide), the beta-human chorionic gonadotropin levels returned to normal. To our knowledge, this is the fourth case of pure choriocarcinoma in the bladder, with the longest survival time of 33 months so far.

The European Association of Urology (EAU) Guidelines Methodology: A Critical Evaluation

OBJECTIVESnGuidelines can be produced and written in numerous ways. The aim of the present article is to describe and evaluate the method currently used to produce the European Association of Urology (EAU) guidelines.nnnDESIGN, SETTING, AND PARTICIPANTSnThe methodology is described in detail, compared to other urologic guidelines by members of the EAU Guidelines Office Board.nnnMEASUREMENTSnThe new methodology is evaluated by the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument.nnnRESULTS AND LIMITATIONSnThe currently used methodology is adapted to the aims and objectives as established by the EAU for their guidelines; wide coverage (essentially all fields of urology) and useful to urologists all over Europe. The frequent updates are easily accessible in a printed and electronic format. The AGREE instrument supports these strong points, but also identifies potentially weak points, such as no patient involvement, no formal validation of the guidelines texts prior to publication, and lack of discussion of organisational barriers and cost implications.nnnCONCLUSIONnThe currently used methodology for the production of EAU guidelines fulfils the associations main objectives related to their guidelines, but the texts will benefit from the inclusion of country-specific cost and organisational data. For the practising clinician, these guidelines will help to take science into clinical practice.

The ideal analgesic treatment for acute renal colic--theory and practice.

Objective. With an annual incidence of 0.1–0.4%, renal colic is certainly a frequent disorder. Thanks to recent findings, the approach to treatment is changing. This prompted us to conduct a survey amongst all urologists in Switzerland regarding the analgesic measures they use in patients suffering from acute renal colic. Material and methods. In March 2005, we sent a total of 170 questionnaires to all practising urologists who are also members of the Swiss Urology Society. The questions covered the types of drugs used for first- and second-line analgesic therapy in acute renal colic and the approach to acute and follow-up analgesic therapy. Dosage adjustments in patients with renal failure were also included. The responses were compared with recent literature findings and international guidelines. Results. The response rate was 58%. Non-opioid analgesics are used for first-line therapy by 81% of respondents, with metamizol being used in 64% of cases. First-line therapy is given intravenously in 65% of cases. An opioid (pethidine) is used most frequently as acute second-line therapy (74% of cases). In the presence of renal failure, half of the respondents make a dose adjustment to the analgesic. Follow-up therapy consists mainly of non-steroidal anti-inflammatory drugs (75%). This complies with the literature and with the recommendations of the European Association of Urology. Conclusion. First-line therapy for acute renal colic should consist of a non-opioid analgesic, and only if the response to this is inadequate should opioids then be used.