[Therapy choices of German urologists and radio-oncologists if personally diagnosed with localized prostate cancer]. / Bevorzugte Behandlungsoptionen des lokalisierten Prostatakarzinoms von deutschen Urologen und Radioonkologen bei eigener Erkrankung.

INTRODUCTION: We evaluated the currently preferred primary treatment options among German urologists and radio-oncologists if personally diagnosed with localized prostate cancer, taking into consideration the different prognostic risk groups. MATERIALS AND METHODS: A questionnaire was mailed to 3,217 urologists and 598 radio-oncologists. They were asked to choose their preferred primary treatment option if they were personally diagnosed with prostate cancer, taking into consideration the different prognostic risk groups: low risk [Gleason score < or =6, prostate-specific antigen (PSA) < or =10 microg/l, T1c], intermediate risk (Gleason score 7, PSA 11-19 microg/l, T2), and high risk (Gleason score > or =8, PSA> or =20 microg/l, T3). Surgical options were further subdivided according to technique (retropubic, laparoscopic, perineal). RESULTS: The questionnaire return rate was 49% for urologists and 41% for radio-oncologists. The mean age was 48 years (28-86) for urologists and 47 years (29-68) for radio-oncologists. Primary surgical treatment was selected by 62% of urologists for low-risk prostate cancer, 90% for intermediate-risk prostate cancer, and 77% for high-risk prostate cancer. Radiotherapy as a primary treatment option was elected by 71% of radio-oncologists for low-risk prostate cancer, 84% for intermediate-risk prostate cancer, and 89% for high-risk prostate cancer. Retropubic, laparoscopic, and perineal prostatectomy would be chosen by 61%, 28%, and 10% of urologists, respectively, for low-risk prostate cancer; by 70%, 24%, and 6%, respectively, for intermediate-risk prostate cancer, and by 80%, 15%, and 5%, respectively for high-risk prostate cancer. CONCLUSION: Urologists prefer surgery and radio-oncologists radiotherapy for primary treatment of prostate cancer, irrespective of the prognostic risk group. Particularly for high-risk prostate cancer, the majority of radiooncologists would still choose radiotherapy as a primary treatment option. In the age of minimally invasive surgery, radical retropubic prostatectomy is still the preferred surgical treatment option among urologists for any prognostic risk group.

Manifestation of congenital urethral diverticula in a 57-year-old male.

Congenital urethral diverticula are a rare finding in adult males. Most cases are diagnosed in childhood or adolescence because of voiding symptoms such as urinary dribbling. Diagnostic workup should include radiography and urethroscopy. The standard therapeutic approach is open surgical excision or endoscopic marsupialization. An unusual case of male congenital urethral diverticula that remained asymptomatic until age 57 is presented.

Do we truly see what we think we see? The role of cognitive bias in pathological interpretation.

In the histomorphological grading of prostate carcinoma, pathologists have regularly assigned comparable scores for the architectural Gleason and the now-obsolete nuclear World Health Organization (WHO) grading systems. Although both systems demonstrate good correspondence between grade and survival, they are based on fundamentally different biological criteria. We tested the hypothesis that this apparent concurrence between the two grading systems originates from an interpretation bias in the minds of diagnostic pathologists, rather than reflecting a biological reality. Three pathologists graded 178 prostatectomy specimens, assigning Gleason and WHO scores on glass slides and on digital images of nuclei isolated out of their architectural context. The results were analysed with respect to interdependencies among the grading systems, to tumour recurrence (PSA relapse > 0.1 ng/ml at 48 months) and robust nuclear morphometry, as assessed by computer-assisted image analysis. WHO and Gleason grades were strongly correlated (r = 0.82) and demonstrated identical prognostic power. However, WHO grades correlated poorly with nuclear morphology (r = 0.19). Grading of nuclei isolated out of their architectural context significantly improved accuracy for nuclear morphology (r = 0.55), but the prognostic power was virtually lost. In conclusion, the architectural organization of a tumour, which the pathologist cannot avoid noticing during initial slide viewing at low magnification, unwittingly influences the subsequent nuclear grade assignment. In our study, the prognostic power of the WHO grading system was dependent on visual assessment of tumour growth pattern. We demonstrate for the first time the influence a cognitive bias can have in the generation of an error in diagnostic pathology and highlight a considerable problem in histopathological tumour grading.

[Stress proteins in prostate cancer. Challenge and promise]. / Stressproteine bei der Pathogenese des Prostatakarzinoms. Herausforderung und Versprechen an die Zukunft.

Therapeutic resistance is the underlying basis for most cancer deaths. Exposure to anticancer therapies induces expression of many stress proteins, including heat shock proteins and clusterin. These molecular chaperones interact with various client proteins to assist in their folding and enhance cellular recovery from stress conditions. Cellular stress and cell death are linked, as the induction of chaperones appear to function at key regulatory points in the control of apoptosis. On this basis and on the role of stress proteins in the regulation of steroid receptors, kinases, caspases, and other protein remodeling events, it is not surprising that molecular chaperones have been implicated in resistance to anticancer treatments. Recently, several chaperones have been reported to be involved in development and progression of hormone-refractory prostate cancer. In this review, we address some of the events initiated by treatment-induced stress and discuss the potential role of chaperone inhibitors in prostate cancer treatment.

[Urethroplasty and simultaneous perineal prostatectomy after traumatic urethral disruption and carcinoma of the prostate]. / Harnröhrenplastik nach Urethraabriss und simultane perineale Prostatektomie.

We present a case of post-traumatic posterior urethral stricture and localized prostate cancer, which could be treated successfully with simultaneous radical perineal prostatectomy and membranous urethral stricture excision. After 6 months follow-up, the patient is continent with no evidence of stricture recurrence. Post-traumatic posterior urethral strictures can be managed surgically through a perineal approach with high success rates. Prostate surgery after pelvic fracture with posterior urethral distraction defects does not necessarily lead to stress urinary incontinence.

Pudendal nerve branch injury during radical perineal prostatectomy.

We report the first case of direct surgical injury to a pudendal nerve branch during radical perineal prostatectomy. A 65-year-old patient presented with typical symptoms of a pudendal nerve lesion after radical perineal prostatectomy. As the patient did not respond to conservative treatment, surgical exploration and exeresis of the injured sensory branch of the pudendal nerve was necessary, resulting in pain improvement. Urologic surgeons should be aware of the typical symptoms after iatrogenic injury to the pudendal nerve or its branches. Early diagnosis and neurosurgical intervention are important to obtain a more favorable outcome.

[Drug therapy of female urinary incontinence]. / Medikamentöse Therapie der weiblichen Harninkontinenz.

Drug treatment for female urinary incontinence requires a thorough knowledge of the differential diagnosis and pathophysiology of incontinence as well as of the pharmacological agents employed. Pharmacotherapy has to be tailored to suit the incontinence subtype and should be carefully balanced according to efficacy and side effects of the drug. Women with urge incontinence require treatment that relaxes or desensitizes the bladder (antimuscarinics, estrogens, alpha-blockers, beta-mimetics, botulinum toxin A, resiniferatoxin, vinpocetine), whereas patients with stress incontinence need stimulation and strengthening of the pelvic floor and external sphincter (alpha-mimetics, estrogens, duloxetine). Females with overflow incontinence need reduction of outflow resistance (baclofen, alpha-blockers, intrasphincteric botulinum toxin A) and/or improvement of bladder contractility (parasympathomimetics). If nocturia or nocturnal incontinence are the major complaints, control of diuresis is obtained by administration of the ADH analogue desmopressin. Future developments will help to further optimize the pharmacological therapy for female urinary incontinence.

[Changes in the receptor profile of the aging bladder]. / Veränderungen des Rezeptorprofils der alternden Blase.

Future demographic developments will challenge urology with a steadily increasing incidence of lower urinary tract symptoms (LUTS) derived from the aging bladder. Obstruction, instability and hypocontractility, which may be caused by changes in the receptor profile of the detrusor, are typical pathophysiologic findings in geriatric bladder dysfunction. Benign prostatic hyperplasia and diabetes mellitus are age-associated comorbidities with an additional influence on bladder receptors. Muscarinic (M(2), M(3)), purinergic (P2X, P2Y) and adrenergic receptors (alpha(1), beta(3)) are targets of efferent sympathetic and parasympathetic bladder innervation. Although the results from animal experiments are somewhat inconsistent, aging and bladder outlet obstruction (BOO) probably cause partial cholinergic denervation of the detrusor with a subsequent upregulation of muscarinic receptor sensitivity leading to bladder instability. The non-cholinergic (atropine-resistant) component of the detrusor contraction rises with aging and BOO to 50%, emphasizing the increasing impact of purinergic receptors in geriatric LUTS. alpha(1)-adrenergic receptors are modulated in the aging bladder by a shift from the predominant alpha(1a) subtype to the alpha(1d) subtype, which shows 100-fold higher affinity towards norepinephrine and increases alpha-adrenergic bladder susceptibility. No data are available on the changes in beta(3) receptor density or sensitivity with aging. Moreover, the role of sensory C-fiber receptors in geriatric LUTS remains completely unclear, although specific C-fiber blockers are already under clinical evaluation (capsaicin, resiniferatoxin).

Perineal complications following radical perineal prostatectomy.

PURPOSE: Radical perineal prostatectomy has recently attracted renewed interest and wider acceptance as an alternative route to the retropubic approach. While presumed lower morbidity is one reason for perineal prostatectomy we evaluated our patients for complications that are specific for the perineal approach. PATIENTS AND METHODS: We have retrospectively analyzed 412 patients who underwent perineal prostatectomy from 10/1996 to 12/2000. Patients for the perineal approach were selected on the base of preoperative PSA (10 ng/ml) and biopsy Gleason score (< 7) without the need for simultaneous lymphadenectomy. A cystogram was performed routinely on day 7 p. o. and the catheter removed when patent anastomosis was confirmed. Intra-, peri- and postoperative complications were recorded and evaluated. RESULTS: Intraoperative complications encompassed 22 cases of rectal injury (5.5 %) with standard primary 2-layer closure, however 4 patients subsequently developed a stool fistula and 3 required a colostomy. Hematoma in the prostatic fossa was diagnosed in 21 patients (5.2 %) and was removed surgically due to infection or increasing size in 4 patients. In 6.5 % of the patients acute urinary retention occurred after catheter removal (91 % after 7 days), while 4.2 % showed urinary extravasation via the perineal wound. Both incidents healed uneventfully with prolonged catheterization in all except 2 cases with concomitant hematoma in whom open fistula closure with a tunica vaginalis graft was performed. The rate of perioperative transfusion was 6.4 %, transient paresthesia and weakness of the leg were observed in 3 patients. CONCLUSIONS: Radical perineal prostatectomy seems to be a procedure with a low rate of complications and surgical reinterventions. However, the spectrum of observed complications is different to that of retropubic prostatectomy and requires specific management.

Simplified orthotopic ileocecal pouch (Mainz pouch) for bladder substitution.

OBJECTIVE: To report operative modifications that render construction of the orthotopic Mainz pouch more simple, namely formation of the pouch using absorbable staples and utilization of the ileocecal valve as an antireflux mechanism. PATIENTS AND METHODS: Between January 2001 and May 2002 out of 92 cystectomy cases, 21 patients (20 males and 1 female) underwent a simplified orthotopic Mainz pouch. The ureters were implanted via Wallace or Nesbit technique in the supravalvular portion of the ileocecal valve. The mean (range) age was 58 (43 - 74) years and the mean follow-up is 11.6 months (range 1 - 27). RESULTS: No staple-related complications were encountered. Four renal units (8.8 %) were dilated, one secondary to an impacted ureteral stone and three secondary to ureteral stenosis requiring reimplantation. At 6 months follow-up, 5 renal units showed reflux (11.1 %) but without any clinical symptoms. 86.5 % of patients void spontaneously without significant residual urine. Continence was achieved in 74 % of cases during day and in 74 % at night. CONCLUSION: The simplified Mainz pouch is a versatile form of continent urinary diversion. The use of absorbable staples has simplified the pouch creation and yields functional results which favorably compare with other pouch forms. The ileocecal valve serves as an anti-reflux-mechanism.

The percentage of free prostate-specific antigen does not predict extracapsular disease in patients with clinically localized prostate cancer before radical prostatectomy.

OBJECTIVE: To determine whether the percentage of free/total prostate-specific antigen (f/tPSA) can predict the pathological features in patients with clinically localized prostate cancer before radical prostatectomy. PATIENTS AND METHODS: Univariate and multivariate logistic regression was used to analyse data from 171 untreated patients who underwent radical prostatectomy. Variables included the total PSA (tPSA), fPSA, f/tPSA, biopsy Gleason score, clinical stage and patient age. RESULTS: In 115 patients with pathologically organ-confined tumours ( pT2N0) the mean (SD) tPSA value was 6.9 (5.6) ng/mL; in 56 patients with extracapsular disease ( pT3pN0/N+) it was 10.2 (7.6) ng/mL; the respective f/tPSA values were 14.9 (8.1)% and 14.2 (12.9)%. In the univariate and multivariate analysis, tPSA and biopsy Gleason score were highly significant in predicting extracapsular disease (P < 0.001 and 0.002) but the f/tPSA was not (P = 0.18). There was no significant difference between the mean f/tPSA and final Gleason scores. CONCLUSION: The f/tPSA does not predict extracapsular disease in patients with clinically localized prostate cancer before radical prostatectomy. Knowing the f/tPSA provides no significant additional information in predicting extracapsular disease when the biopsy Gleason score and tPSA are known.

Low urethral pressure profile--clinical implications.

The clinical impact of urethral pressure profilometry (UPP) has been a main urological topic over the past three decades. Exaggerated expectations and differing techniques with incongruent results caused a controversial appearance. However, since the UPP is the only method to measure directly aspects of the urethral closure function, all types of sphincteric urinary incontinence represent indications for this measurement. Based on long-term experience this paper aims to discuss the various complexes regarding the urethral pressure profilometry. The significance of the urethral closure function for urinary continence and the urodynamic relevance of active and passive pressure transmission are described. In addition, clinical implications in terms of therapeutic strategies to treat urinary stress incontinence with regards to a low urethral pressure profile are presented.

Effects of phenylbutyrate on proliferation and apoptosis in human prostate cancer cells in vitro and in vivo.

Phenylbutyrate (PB) is a potent differentiating agent and currently under investigation for the treatment of prostate cancer (CaP) and other malignancies. We have studied the impact of PB in vitro and in vivo on differentiation, proliferation and apoptosis in the LNCaP and LuCaP 23.1 prostate cancer xenograft models. In vitro we found that i) PB increased PSA secretion/cell, ii) inhibited cell proliferation in a time- and dose-dependent manner resulting in a cell cycle arrest in G1-phase and iii) induced apoptosis at concentrations of 2.5 mM after 3 days of treatment. In PB treated animals tumor growth stabilized or regressed. Combination of castration and PB treatment had a synergistic antiproliferative effect. The growth-inhibitory and differentiating properties and a low toxicity profile of PB provide rationale for further clinical studies in patients with CaP.

Detection of circulating prostate cells by reverse transcriptase-polymerase chain reaction of human glandular kallikrein (hK2) and prostate-specific antigen (PSA) messages.

OBJECTIVES: To investigate the clinical value of human glandular kallikrein (hK2) reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of prostate cells in circulation and to compare the results with those obtained from prostate-specific antigen (PSA) RT-PCR. METHODS: We examined peripheral blood (PB) and bone marrow (BM) samples of 13 patients with advanced-stage prostate cancer and 63 patients with clinically localized disease for the presence of circulating prostate cells. An RT-PCR protocol with a two-step amplification cycle and hot-start conditions was used. RESULTS: The limit of detection of the PCR portion is similar for PSA and hK2 (5 to 10 copies of the plasmid containing the cDNA). The RT-PCR limit of detection is one LNCaP cell in 10(8) peripheral blood mononuclear cells (PMBC) for PSA, and one LNCaP cell in 10(7) PMBC for hK2. Of the BM samples obtained prior to radical prostatectomy, 71.4% were positive for PSA mRNA and 41.3% were positive for hK2 mRNA. In PB, the PSA positivity was 19% and hK2 positivity 12.7%. In advanced-stage patients, there were 76.9% PSA-positive samples in BM versus 38.5% hK2-positive samples; 46.2% of patients were positive in PB for PSA versus 30.8% for hK2. CONCLUSIONS: We have developed a sensitive RT-PCR protocol for detection of hK2 mRNA and evaluated the suitability of hK2 mRNA in comparison with PSA mRNA as an additional marker for detection of prostate cells in circulation. Combining results of these two tests increased the sensitivity of detection.

Early tumor cell dissemination in patients with clinically localized carcinoma of the prostate.

Because a significant number of patients with pathologically organ-confined carcinoma of the prostate subsequently develop recurrent disease, metastasis may occur much earlier than previously believed. We have used a reverse transcription-PCR assay for prostate-specific antigen mRNA and an immunocytochemical staining method for cytokeratins to test this hypothesis in paired peripheral blood (PB) and bone marrow (BM) specimens from 71 patients with clinically localized disease before radical prostatectomy, 14 patients with advanced-stage carcinoma of the prostate, and 30 controls (young healthy volunteers, patients without prostate disease, and patients with benign prostatic hyperplasia). Controls were negative in BM and PB. Fifty-six% of patients with organ-confined tumors (pT2) and 73% of those with extracapsular extension (pT3) were positive in the BM versus 16% of those with pT2 tumors and 27% of those with pT3 tumors in the PB. Patients with advanced-stage disease were positive in 86% of BM versus 71% of PB. The sensitivity of the immunocytochemistry assay to detect tumor cells was lower as compared with the reverse transcription-PCR assay. The results suggest that tumor cell dissemination occurs early during disease progression. Prostate cells seem to preferentially concentrate in the BM rather than the PB, which may be due to sequestration there by homing mechanisms. As the rate of detection in the BM exceeds the proportion of patients with subsequently progressing disease, we hypothesize that only a subset of these cells can survive in the BM and evolve to clinically apparent disease.

Role of transrectal ultrasound and prostate biopsy.

Transrectal ultrasound (TRUS) has revolutionized our ability to image the human prostate. In the present review, we have attempted to present salient observations with respect to this modality. We emphasize its use in combination with biopsy in men who are considered at risk for harboring carcinoma. The relevant English literature is reviewed. In addition, our experience with 2,231 consecutive ultrasound-guided biopsies performed at the University of Washington and the Seattle VA Medical Center is analyzed. TRUS appears to have its primary use in directing the biopsy needle into suspicious areas and in performing the so-called systematic sector approach to biopsy. The role of transrectal ultrasound in staging established malignancy or in monitoring men following therapy remains to be defined. In our experience, carcinoma was detected in 27.2% of the subjects. Carcinoma was found in 30.7% of patients with a hypoechoic sector. Of note, 18.4% of men had their only carcinoma found in isoechoic areas. Failure to biopsy isoechoic sectors would have resulted in missing almost 20% of men with carcinoma. The role of TRUS in men with initially negative biopsy is also discussed. In summary, ultrasound guided biopsy is a useful addition to our armamentarium, particularly with respect to performing biopsy. Future advances in this modality include image enhancement utilizing computer technology as well as the potential additive role of color flow ultrasound.

[Nuclear medicine diagnosis and therapy in urology. Diagnosis of bone metastases]. / Nuklearmedizinische Diagnostik und Therapie in der Urologie. Diagnostik von Knochenmetastasen.

Bone scintigraphy with 99mtechnetium-labelled polyphosphonates is the most sensitive test for early detection of skeletal metastases. Bone metastases are a major factor in prognosis and have a considerable influence on the therapy selected. In patients with prostate cancer, we recommend routine bone scintigraphy in the initial staging. Follow-up bone scans are indicated whenever a patient develops pain, an elevated level of acid phosphatase, or a rise in prostate specific antigen (PSA). Routine bone scans are not necessary for the initial staging of patients with renal cell carcinomas, bladder carcinomas and testicular tumours. Scans should be routinely performed, however, in patients with bone pain or elevated alkaline phosphatase or when radiological findings are inconclusive. Bone scanning is necessary in patients with neuroblastoma, both for the initial diagnosis and during follow-up in all cases with known skeletal involvement. In addition, bone scintigraphy should be performed in cases of recurrent or suspected malignant phaeochromocytoma as a complement to scintigraphy with iodine-123- or iodine-131-MIBG, respectively. Even though skeletal scintigraphy is a very sensitive test, it lacks specificity. This can be compensated, however, by careful interpretation of the scan in the light of the patient's history and the clinical findings. As a positive side-effect, bone scanning--especially in the form of multiphase scintigraphy--may detect renal abnormalities, concurrent diseases or complications in the upper or lower urinary tract. If scintigraphic findings are doubtful, plain film radiographs are required or, in selected cases, bone biopsy must be performed.