Immediate versus deferred hormonal treatment for patients with prostate cancer who are not suitable for curative local treatment: results of the randomized trial SAKK 08/88.

PURPOSE: To determine if immediate hormonal therapy is advantageous compared with deferred treatment in newly diagnosed asymptomatic prostate cancer patients who, for any reason, were not candidates for curative local treatment. PATIENTS AND METHODS: Between February 1988 and February 1992, 197 patients with a median age of 76 years (range, 56 to 86 years) were randomly assigned to receive either immediate or deferred orchiectomy on symptomatic progression. The two groups did not differ significantly in clinical or laboratory parameters; 67% had T3-4 tumors and 20% had lymph node metastases. Patient accrual was stopped prematurely because of a similar competing trial. Therefore, observation time was prolonged to achieve the desired number of events and statistical power. RESULTS: Deferred orchiectomy was necessary in 58% of the patients. Median time to disease progression was 2.8 years less than for patients with immediate orchiectomy. However, overall pain-free time from random assignment to symptomatic progression after immediate or deferred orchiectomy, and performance status, were identical in both groups. Cancer-specific survival tended to be longer in the immediate group (P = .09) but there was no difference in overall survival between the two groups (P = .96). The median hemoglobin value decreased significantly after immediate orchiectomy (P < .001). CONCLUSION: For elderly, asymptomatic patients not undergoing curative local treatment, we were unable to show any major advantage of immediate compared with deferred hormonal treatment regarding quality of life or overall survival in our limited number of patients. Disabling complications were prevented in the deferred-treatment arm by careful follow-up; 42% of these patients never required any tumor-specific treatment.

Peri-operative morbidity and changes in symptom scores after transurethral prostatectomy in Switzerland: results of an independent assessment of outcome.

OBJECTIVES: To assess, in a prospective study, the contemporary outcome of transurethral resection of the prostate (TURP) in patients with benign prostatic hyperplasia (BPH) in Switzerland, by evaluating peri-operative morbidity and changes in lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Between January 2000 and January 2005, 11 hospitals in Switzerland participated in the study. The hospitals were required to inform Verein Outcome (VO), an independent institution specialising in outcome measurements in the Swiss healthcare system, about patients with BPH who were scheduled for TURP. Later, the hospitals provided data on peri-operative complications in these patients. The patients' Danish Prostate Symptom Score (DAN-PSS) was obtained by VO before and 4 months after TURP (via mailed questionnaires). RESULTS: Data on peri-operative complications from 1014 patients were included in this analysis. The mean (range) age of the patients was 69 (43-91) years. The most common complication after TURP was urinary retention, in 4.5% of the patients; the overall peri-operative complication rate was 9%. In all, 468 patients returned questionnaires both before and after TURP. The mean total DAN-PSS before and 4 months after surgery was 25.2 and 6.2, respectively (P < 0.001). CONCLUSIONS: The results of this prospective multicentre study showed that the current peri-operative morbidity of TURP is lower than that reported from older large-scale trials. The independent assessment of symptom scores confirms that TURP is highly effective in alleviating bothersome LUTS due to BPH.

Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891.

PURPOSE: This study (EORTC 30891) attempted to demonstrate equivalent overall survival in patients with localized prostate cancer not suitable for local curative treatment treated with immediate or deferred androgen ablation. PATIENTS AND METHODS: We randomly assigned 985 patients with newly diagnosed prostate cancer T0-4 N0-2 M0 to receive androgen deprivation either immediately (n = 493) or on symptomatic disease progression or occurrence of serious complications (n = 492). RESULTS: Baseline characteristics were well balanced in the two groups. Median age was 73 years (range, 52 to 81). At a median follow-up of 7.8 years, 541 of 985 patients had died, mostly of prostate cancer (n = 193) or cardiovascular disease (n = 185). The overall survival hazard ratio was 1.25 (95% CI, 1.05 to 1.48; noninferiority P > .1) favoring immediate treatment, seemingly due to fewer deaths of nonprostatic cancer causes (P = .06). The time from randomization to progression of hormone refractory disease did not differ significantly, nor did prostate-cancer specific survival. The median time to the start of deferred treatment after study entry was 7 years. In this group 126 patients (25.6%) died without ever needing treatment (44% of the deaths in this arm). CONCLUSION: Immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival but no significant difference in prostate cancer mortality or symptom-free survival. This must be weighed on an individual basis against the adverse effects of life-long androgen deprivation, which may be avoided in a substantial number of patients with a deferred treatment policy.

Micturition Syncope due to paraprostatic pheochromocytoma.

Paraprostatic pheochromocytoma is a very rare localization of extra-adrenal pheochromocytoma. The clinical and anatomical features of a 41-year-old man are described.

Bilateral perirenal lymphangioma: a conservative approach.

The lymphangioma is a well-recognized benign tumor most frequently encountered in infancy and childhood. The kidneys are rarely involved. Despite its benign nature, most of the patients were treated by partial or radical nephrectomy. We describe a case of bilateral perirenal lymphangioma in a 33-year-old man for whom we chose a conservative approach.

Chronic scrotal pain syndrome: management among urologists in Switzerland.

INTRODUCTION AND OBJECTIVES: Management of patients presenting with chronic or recurrent pain located in the scrotum is often very challenging. Evidence-based literature and clinical practice guidelines for the management of chronic scrotal pain syndrome (CSPS) are not available. We assessed the current perception and management of chronic scrotal pain syndrome by urologists in Switzerland. METHODS: In July 2004, all the members of the Swiss Society of Urology received a questionnaire focusing on diagnostic and treatment practices for the management of chronic scrotal pain syndrome. The questionnaire consisted of 6 topics concerning practice setting, incidence, aetiology, diagnostics, therapy and treatment success rate. RESULTS: 103 questionnaires were completed (63%). All but 2 (2%) responding Swiss urologists see a mean of 6.5 new patients per month (range 1-30). 79% of Swiss urologists consider CSPS to be infectious or post-infectious in nature. Furthermore, a history of vasectomy, psychosomatic disorders, chronic prostatitis, neuromuscular disorders, a history of inguinal surgery, and idiopathic aetiology were mentioned in decreasing order. The most commonly used examinations are urinalysis in 96% and ultrasound in 93%. Additional assessments include blood sampling, duplex ultrasound, assessment for coexisting chronic prostatitis, and referral to an Orthopaedist, Rheumatologist or Psychiatrist. The predominant medication prescribed for CSPS is a non-steroidal anti-inflammatory agent given for a mean of 15.5 days. An antibiotic trial is prescribed by 82% for a mean of 20.5 days. 74% consider epididymectomy the treatment option of choice in recurrence. Inguinal orchiectomy is performed by 7%, microsurgical spermatic cord denervation is performed by 6% of surgeons. Mean estimated recurrence rate after conservative treatment is 48% and thus higher than after epididymectomy with 18%. CONCLUSIONS: Chronic pain located in the scrotum is a common clinical condition in Switzerland. Most urologists consider an infection or post-infectious alterations as the predominant aetiology for CSPS. Consequently, an antibiotic trial in combination with an anti-inflammatory agent is prescribed as first-line therapy. Recurrence rates for conservative treatment are estimated high which is in contradiction to the presumed aetiology. Therefore, further evaluation of this poorly described disease complex is required.

Pain and its treatment in urology.

Although untreated/undertreated pain leads to a variety of somatic, psychological and socioeconomic harm, the knowledge of its physiology, diagnosis and adequate treatment is generally low among urologists. This review has the primary goal to sensitize us urologists to this underrated topic.

Effect of radical prostatectomy on urethral blood flow.

OBJECTIVES: To study the effect of radical retropubic prostatectomy on urethral microcirculatory blood perfusion and urinary continence. Urinary stress incontinence after radical prostatectomy depends mainly on intrinsic distal sphincter integrity. METHODS: Urethral laser Doppler flowmetry was performed in 37 patients before and in 23 patients after (mean 15 months, range 2 to 23) radical prostatectomy for clinically localized prostate cancer. An endoscopic laser Doppler flow probe with a diameter of 1.8 mm was introduced through the working channel of a cystoscope and gently applied to the urethral mucosa at an intravesical pressure of 30 cm H(2)O. Blood flow was expressed simultaneously as a digital reading on the flowmeter (milliliters blood per minute per 100 gram tissue). The mean arterial blood pressure was monitored noninvasively. The Mann-Whitney U test was used for statistical analysis. RESULTS: Membranous urethral blood flow significantly decreased after radical prostatectomy from 18.8 +/- 7.9 mL/min per 100 gram tissue to 11.9 +/- 7.7 mL/min per 100 gram tissue (P = 0.04). However, the difference in the blood flow did not statistically differentiate continent patients from patients with urinary stress incontinence (P = 0.47). No correlation between urethral microcirculation and mean arterial blood pressure could be detected. CONCLUSIONS: Retropubic radical prostatectomy decreases membranous urethral microcirculation. However, this loss of vascularization does not have a major effect on distal sphincter function and continence after radical prostatectomy.

Impact of prostatitis NIH IIIB (prostatodynia) on ejaculate parameters.

OBJECTIVES: Prostatitis NIH IIIB is defined by chronic pelvic pain without evidence of inflammation in prostate secretions or ejaculate. The relations between chronic prostatitis and fertility are discussed controversially. In this context, we analysed fertility data of a well defined collective of patients with prostatitis NIH IIIB. METHODS: We analysed prospective fertility data of a group of 30 patients with chronic prostatitis NIH IIIB and compared these data with the duration of symptoms as well as with an age-matched control group. RESULTS: The prostatitis group and the control group differed significantly in terms of ejaculate volume, motility and fructose concentration. The remaining parameters did not differ significantly. An azoospermia was present in 3 patients of the prostatitis group versus none of the control group. The duration of symptoms did not correlate with the sperm parameters (sperm density, motility and morphology). CONCLUSIONS: Patients with prostatitis NIH IIIB have changes in their ejaculate with a reduction of motility and a reduced fructose concentration. This supports a somatic aetiology of the chronic pelvic pain syndrome.

Long-term experience with surgical and conservative treatment of penile fracture.

PURPOSE: Immediate surgical repair is widely accepted as the therapy of choice in penile fracture. As recent reports show, good results can also be achieved in some patients with conservative management. It is unclear which patients will truly benefit from an operation. We retrospectively compared the long-term outcomes of surgical and conservative treatment in patients with penile fracture. MATERIALS AND METHODS: In 22 years we treated 29 patients with penile fracture. A total of 12 patients were treated with immediate surgical repair and 17 patients were treated conservatively. Patient charts were reviewed and all patients had followup by interview with an additional clinical evaluation if the result was not completely satisfactory. Outcome was rated good, moderate or poor. RESULTS: Mean followup was 67 months. There was no statistical difference between patients in the surgery group and patients in the conservative group in regard to length of followup, age at presentation or length of hospital stay. In the surgery group and the conservative group 11 (92%) and 10 (59%) patients showed good outcome, respectively. Poor outcome was seen in 3 patients from the conservative group. CONCLUSIONS: Overall, immediate surgery yields excellent results and is superior to nonoperative treatment in the management of penile fracture. However, conservative therapy restricted to uncomplicated cases can lead to an equally good outcome.

Evidence of gap junctions in the stable nonobstructed human bladder.

PURPOSE: Gap junctions are thought to synchronize muscle cell actions by promoting intercellular communications. Since it is still a matter of debate whether smooth muscle cells in the bladder are electrically coupled, we investigated the occurrence of gap junctions and the gap junction forming protein connexin 45 in normal human detrusor. MATERIALS AND METHODS: Detrusor smooth muscle was obtained during radical cystectomy in 6 patients. For transmission electron microscopy studies samples were high pressure frozen and cryo-fixed. Additional frozen samples were processed for freeze fracture/freeze fracture immunolabeling analyses or for reverse transcriptase-polymerase chain reaction using primers for connexin 45. Furthermore, a set of samples was fixed with Bouin's solution, embedded in paraffin and used for immunohistochemistry with a polyclonal antibody against connexin 45 as well as for in situ hybridization studies with digoxigenin labeled connexin 45 riboprobes. RESULTS: Ultrastructural and freeze fracture studies showed gap junctions at detrusor smooth muscle cells. However, these gap junctions appeared to be small and irregularly shaped. Reverse transcriptase-polymerase chain reaction and in situ hybridization showed that connexin 45 mRNA was expressed in the detrusor muscularis. Furthermore, we detected prominent connexin 45 immunoreactions at detrusor smooth muscle cells. Freeze fracture immunolabeling techniques revealed connexin 45 signals at small gap junctional plaques. CONCLUSIONS: To our knowledge this study is the first to provide morphological, molecular biological and immunohistochemical evidence that smooth muscle cells of stable human detrusor are electrically coupled through gap junctions. These results may contribute to new concepts in the understanding of bladder physiology.

Urethral evoked sympathetic skin responses and viscerosensory evoked potentials as diagnostic tools to evaluate urogenital autonomic afferent innervation in spinal cord injured patients.

PURPOSE: In most spinal cord injured (SCI) patients the objective assessment of afferent neuronal pathways from the lower urinary tract and the recording of a disturbed urethral sensation and/or desire to void are still difficult. Viscerosensory evoked potentials (VSEPs) might be helpful, but they remain technically difficult to obtain and interpretation is delicate. As a new approach, sympathetic skin response (SSR) of the hand and foot were recorded after electrical stimulation of the posterior urethral mucosa. This technique should allow assessment of the integrity or deterioration of the autonomic afferent pathway. MATERIALS AND METHODS: A total of 20 males and 8 females with SCI somatosensory incomplete 15, somatosensory complete 13 and 6 healthy male volunteers were prospectively examined. During urodynamic examination electrical stimulation (single square pulses of 0.2 ms, 2 to 3-fold sensory threshold, 60 mA in complete SCI patients) of the posterior urethra/bladder neck was performed using a bipolar electrode inserted into a microtip pressure catheter. SSR recordings of the right palm and sole were simultaneously taken using surface electrodes and were analyzed by an electromyography unit. Patient reports on evoked urethral sensations at individual sensory thresholds were simultaneously noted. Additionally, well-known electrophysiological measurements such as pudendal sensory evoked potential and urethral VSEP were recorded to check clinical assessed somatosensory and viscerosensory status, and to compare SSR results with these conventional methods. RESULTS: Electrical stimulation of the posterior urethra evoked clear urethral sensation and SSRs in normal subjects. In 14 of 15 sensory incomplete SCI patients with disturbed urethral sensation SSRs could be recorded as well. Electrically evoked urethral sensations resembled the subjective desire to void at full bladder reported by controls and patients. In 13 sensory complete SCI patients with loss of any urethral sensation SSRs could not be recorded even at maximal electrical stimulation strength. All subjects with electrically induced urethral sensation had positive evoked (supralesional) SSRs of the hand. However, none of the patients with absent urethral sensation presented SSRs. Simultaneously recorded VSEPs could not be recorded clearly in 5 patients and 2 control subjects, whereas SSRs delivered clear results in all controls and patients, matching their reports. CONCLUSIONS: SSR recordings above a spinal lesion level after urethral electrostimulation might provide a useful and technically simple objective diagnostic tool to assess integrity of autonomic (visceral) afferent nerves from the lower urinary tract. Somatosensory deficits are not always paralleled by viscerosensory loss and vice versa. In this study SSRs were superior to VSEPs, the latter being more difficult to record. The subjective sensations reported by subjects during stimulation could be confirmed in an objective way in 100% of cases by positive/negative SSR findings.

A new high frequency electrostimulation device to treat chronic prostatitis.

PURPOSE: We prospectively observed a possible benefit from urethro-anal high frequency electrostimulation in patients with noninflammatory chronic pelvic pain syndrome (Cat IIIB CPPS) as a new treatment option. MATERIALS AND METHODS: A total of 88 patients with a referral diagnosis of chronic prostatitis underwent fractionated urinary cultures, including expressed prostate secretion and ejaculate analysis twice. Of this group 14 men with Cat IIIB CPPS elected electrostimulation. A urethro-anal stimulation device was applied twice weekly for 30 minutes during 5 weeks at a defined voltage of 6 V, a defined frequency of between 450 and 500 Hz, and a variable self-regulated current of between 1 and 10 mA. National Institutes of Health prostatitis symptom score and quality of life index were determined before and after the treatment. RESULTS: All patients tolerated stimulation and completed the treatment course. No urethral or anal complications occurred. Generally, the patients reported a distinct perineal feeling and the pain syndrome improved in 83%. The mean total National Institutes of Health prostatitis symptom score significantly decreased from 29 (range 20 to 37) to 14 (range 8 to 24) points (p = 0.002). Mean pain decreased from 15 (range 12 to 20) to 7 (range 4 to 13) points (p = 0.002). Micturition complaints decreased from 2.5 (range 0 to 9) to 1 (range 0 to 8) points (p = 0.007) and quality of life improved from 9.5 (range 8 to 12) to 5.5 (range 3 to 10) (p = 0.003). CONCLUSIONS: To date the new high frequency urethro-anal afferent electrostimulation device seems to have an important benefit in patients with Cat IIIB CPPS. The device is technically simple and it can be self-administered. Therefore, it may become a new ambulatory treatment option for patients with chronic pelvic pain syndrome.

Occurrence and localization of uroguanylin in the aging human prostate.

Uroguanylin, a peptide hormone highly expressed in the gastrointestinal tract, is implicated in the regulation of epithelial salt and water transport processes. Since little is known about a possible role of uroguanylin in the reproductive system, we investigated for the first time the occurrence of this peptide in the human prostate using specimens of benign prostatic hyperplasia. Northern blot analyses detected a single uroguanylin transcript of approximately 600 bp in prostate RNA. The uroguanylin expression was further investigated by reverse transcriptase polymerase chain reaction of prostate RNA with uroguanylin-specific primers. Sequencing of the fragments obtained indicated the presence of a uroguanylin molecule with a sequence identical to its intestinal counterpart. Furthermore, in situ hybridization and immunohistochemistry revealed that uroguanylin mRNA and peptide are confined to epithelial cells of the prostate glands. Comparison with the distribution pattern of immunoreactivity for prostate-specific antigen (PSA) showed a high degree of colocalization of uroguanylin- and PSA-immunoreactive cells. In addition, by western blotting techniques we detected the presence of high molecular weight uroguanylin-immunoreactive material in prostatic fluid. In conclusion, our study indicates that the human prostate glands synthesize and secrete (pro-)uroguanylin. We hypothesize that this hormone may play a novel role in the male reproductive tract.