The management and outcome of patients with germ-cell tumours treated in the Edinburgh Cancer Centre between 1988 and 2002.

AIMS: The aim of this retrospective analysis was to review the outcome of patients with germ-cell tumours treated in the Edinburgh Cancer Centre over the past 15 years, and to see whether there had been any changes over three 5-year cohorts. MATERIALS AND METHODS: Patients referred with gonadal and extra-gonadal primary germ-cell tumours, between 1988 and 2002, were identified from the departmental database, and survival by stage and prognostic group was analysed. RESULTS AND CONCLUSIONS: The proportion of patients with stage I seminoma has significantly increased. The good prognosis of patients with early stage disease is confirmed, with the outcome for some groups of patients being better than expected. There is a non-significant trend to improved results over the three 5-year cohorts. The outcome for patients with stage IV seminoma is worse than would be expected, but numbers are small. The poor prognosis of patients with non-seminomatous germ-cell tumours who fall into the International Germ Cell Consensus Classification (IGCCC) poor-prognostic group is confirmed. Failure of patients with metastatic non-seminomatous germ-cell tumours to achieve a complete response to initial therapy is shown to be a poor prognostic indicator.

Alfuzosin 10 mg once daily in the management of acute urinary retention: results of a double-blind placebo-controlled study.

OBJECTIVES: To study the impact of alfuzosin 10 mg once daily (OD) on the outcome of a trial without catheter (TWOC) after a first episode of acute urinary retention (AUR) related to benign prostatic hyperplasia (BPH) and the subsequent management of BPH in these patients. METHODS: A total of 360 patients underwent emergency catheterization and were blindly randomized to alfuzosin 10 mg OD or placebo for 3 days (first phase). All patients with successful TWOC, regardless of treatment, were then again blindly randomized to alfuzosin 10 mg OD or placebo for 6 months (second phase). The need for BPH surgery (primary endpoint) was assessed after 1, 3, and 6 months of treatment. RESULTS: Alfuzosin significantly increased the successful TWOC rate (146 of 236, 61.9%) compared with placebo (58 of 121, 47.9%; P = 0.012). In the second phase, 14 (17.1%) of the 82 alfuzosin-treated patients versus 20 (24.1%) of the 83 placebo-treated patients required BPH surgery, 5 (36%) of 14 versus 13 (65%) of 20 within 1 month, and 8 (57%) of 14 versus 17 (85%) of 20 within 3 months of treatment. Emergency surgery because of AUR relapse was the main cause of failure in both groups (11 [78.6%] of 14 in the alfuzosin group and 16 [80.0%] of 20 in the placebo group). Compared with placebo, alfuzosin improved the Kaplan-Meier survival rates by 9.6% (P = 0.04), 11.4% (P = 0.04), and 8.3% (P = 0.20), with surgical risk reductions of 61%, 52%, and 29% at 1, 3, and 6 months of treatment, respectively. High prostate-specific antigen values and the post-TWOC residual urine volume significantly increased the risk of AUR relapse and BPH surgery. Alfuzosin 10 mg OD was well tolerated. CONCLUSIONS: Alfuzosin 10 mg OD increased the likelihood of successful TWOC in men with a first episode of spontaneous AUR and should be continued beyond the acute phase, as it reduced the need for BPH surgery during a 6-month treatment period.

Alfuzosin once daily facilitates return to voiding in patients in acute urinary retention.

PURPOSE: We confirmed the beneficial effect of the alpha1-blocker alfuzosin for the acute management of acute urinary retention (AUR) related to benign prostate hyperplasia (BPH), and further identified factors influencing the success of a trial without catheter (TWOC). MATERIALS AND METHODS: A total of 360 patients presenting with a first episode of spontaneous AUR related to BPH underwent emergency catheterization and were then randomly and blindly assigned to receive 10 mg alfuzosin once daily or placebo at a ratio of 2:1 for 3 days. The primary efficacy criterion of this large study was the rate of successful TWOC within 24 hours after catheter removal. The influence of factors such as age, urine retention volume, fluid consumption, constipation and urinary tract infection on TWOC outcome was also assessed. RESULTS: Successful TWOC was recorded in 61.9% of the 236 patients treated with alfuzosin vs 47.9% of the 121 receiving placebo (p = 0.012). Elderly patients (65 years or older) and patients with a drained volume of 1000 ml or greater had significantly greater chances of TWOC failure (success vs failure OR 0.309, 95% CI 1.182 to 0.514 and OR 0.361, 95% CI 0.225 to 0.571, respectively). Nevertheless, even in the presence of these 2 factors 10 mg alfuzosin once daily almost doubled the likelihood of successful TWOC (OR 1.98, 95% CI 1,226 to 3,217). Alfuzosin (10 mg) once daily was well tolerated. CONCLUSIONS: Alfuzosin (10 mg) once daily significantly improved the rate of successful TWOC in patients with AUR related to BPH, even in elderly patients and those with a large drained volume who were at increased risk for TWOC failure. This should contribute to decrease the morbidity and mortality associated with emergency surgery and avoid the discomfort and potential morbidity associated with an in situ catheter.

Nesbit procedure for disabling Peyronie's curvature: a median follow-up of 84 months.

OBJECTIVES: To assess patient satisfaction with cosmetic and functional results after surgical correction for symptomatic penile curvature with the Nesbit procedure using postal questionnaire follow-up. METHODS: From 1991, 57 patients underwent surgery for a penile bend of greater than 30 degrees that was interfering with sexual function. Fifteen patients had mild to moderate erectile dysfunction on the preoperative assessment. In all patients, correction of curvature was performed by the Nesbit procedure after adequate preoperative counseling and informed consent. All patients were sent a questionnaire, and 42 men (76.4%) responded. The confidentiality of records was maintained at all times. RESULTS: Our study shows that 38 patients (90.5%) had either a straighter penis (n = 26) or minor degrees of curvature of less than 30 degrees (n = 12); only 4 patients had severe curvature. Seven patients complained of some bumpy and narrowed areas, and nine noticed reduced sensory changes. Twenty-one patients complained of penile shortening but 16 reported that this did not affect their sexual performance. Overall, 32 patients were fairly satisfied with the operation-10 (23.8%) of 42 men reported dissatisfaction because of multiple factors. Of these, 6 patients had responded that they would not have undergone the procedure if they were able to turn the clock back. CONCLUSIONS: Our long-term results after the Nesbit procedure are longer than that reported in any other series. Our results compare favorably with the short-term results of the modified Nesbit procedure, but simple/modified plication surgery results have not been so encouraging.

Mutations at the mitochondrial DNA polymerase (POLG) locus associated with male infertility.

Human mitochondrial DNA polymerase, encoded by POLG, contains a polyglutamine tract encoded by a CAG microsatellite repeat. Analysis of POLG genotypes in different populations identified an association between absence of the common, ten-repeat allele and male infertility typified by a range of sperm quality defects but excluding azoospermia.

Efficacy of sildenafil citrate for the treatment of erectile dysfunction in men taking serotonin reuptake inhibitors.

OBJECTIVE: This study was an evaluation of whether sildenafil citrate is effective for the treatment of erectile dysfunction in men taking concomitant serotonin-reuptake-inhibiting antidepressants. METHOD: A retrospective subanalysis of combined data from 10 phase II/III double-blind, placebo-controlled, fixed- and flexible-dose trials (12-26 weeks) identified a group of men with erectile dysfunction receiving 5 to 200 mg/day of sildenafil (N=65) or placebo (N=33) and concomitant serotonin-reuptake-inhibiting antidepressants. Efficacy was measured by responses to questions from the International Index of Erectile Function on ability to achieve erection, ability to maintain erection, ejaculation frequency, orgasm frequency, and sexual desire. RESULTS: Patients with erectile dysfunction receiving sildenafil and concomitant serotonergic antidepressants had significantly greater improvements in ability to achieve and maintain an erection, frequency of ejaculation, and orgasm frequency than did patients receiving placebo, without increased sexual desire. CONCLUSIONS: Sildenafil significantly improved erectile dysfunction in patients taking concomitant serotonergic antidepressants.

Postvoid residual urine in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: pooled analysis of eleven controlled studies with alfuzosin.

OBJECTIVES: A pooled analysis was conducted in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia to examine the relationship between the postvoid residual urine (PVR) volume and various clinical characteristics and to assess the effect of alfuzosin, a clinically uroselective alpha(1)-blocker, on PVR volume and any other associated outcome. METHODS: Nine hundred fifty-three patients, 42 to 89 years old, with a baseline PVR volume between 50 and 350 mL (mean 106 mL) were enrolled in 11 double-blind controlled studies and received either alfuzosin (n = 607) or placebo (n = 346) for 1 to 6 months. The relationships between the baseline PVR volume measured by transabdominal ultrasound and age, symptoms, maximum flow rate (Qmax), estimated bladder capacity, and prostate-specific antigen level were assessed. The changes in the PVR volume with treatment were evaluated in all available patients at three endpoints (1, 3, and 6 months). RESULTS: At baseline, a PVR volume of 100 mL or greater was observed in 60%, 47%, and 39% of patients with a Qmax less than 8, 8 to 11, and greater than 11 mL/s, respectively (P = 0.001). The bladder capacity was also significantly related to the Qmax (P = 0.0001). No relationship was found between PVR volume and age, symptoms, or prostate-specific antigen level. The changes in the PVR volume with treatment were related to the baseline PVR volume. However, at all endpoints and whatever the baseline PVR volume, the decreases in the PVR volume were significantly (P <0.01) greater with alfuzosin than with placebo. Acute urinary retention occurred in 7 patients (2 [0.3%] of 607 patients taking alfuzosin and 5 [1.4%] of 346 patients taking placebo); 6 of these 7 patients had a baseline PVR volume greater than 100 mL. CONCLUSIONS: In this population of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, the PVR olume and bladder capacity were related to the baseline Qmax. Alfuzosin significantly reduced the PVR volume compared with placebo, and this effect was more marked in patients with a high PVR volume at baseline. Acute urinary retention occurred mainly in patients with a PVR volume greater than 100 mL and was less frequent in patients taking alfuzosin than in those taking placebo.

Assessment of the efficacy and safety of Viagra (sildenafil citrate) in men with erectile dysfunction during long-term treatment.

Long-term efficacy and safety of sildenafil was assessed in 1008 patients with erectile dysfunction (ED) enrolled in four flexible-dose (25 - 100 mg), open-label, 36- or 52-week extension studies. After 36 and 52 weeks, 92% and 89% of patients felt that treatment with sildenafil had improved their erections. Responses to a Sexual Function Questionnaire indicated that 52 weeks of sildenafil treatment resulted in clinically significant improvements in the duration and firmness of erections, overall satisfaction with sex life, and the frequency of stimulated erections. Commonly reported adverse events (AEs) were headache, flushing, dyspepsia, and rhinitis, which were generally mild to moderate. Reports of abnormal vision were consistent with previous clinical trials. The occurrence of treatment-related cardiovascular AEs, such as hypertension, tachycardia, and palpitation, was <1%. Discontinuations due to treatment-related AEs were low (2%). Long-term therapy does not diminish the efficacy of sildenafil in patients with ED and remains well tolerated.

Efficacy of PSA in the detection of carcinoma of the prostate in patients presenting with acute urinary retention.

OBJECTIVES: A temporary elevation in serum-prostate specific antigen (PSA) levels has been reported in association with acute urinary retention. In spite of this, it is not uncommon for clinicians to assay PSA at the time a patient presents with acute urinary retention. We sought to evaluate whether this practice can be justified. PATIENTS AND METHOD: Fifty-four patients, aged between 55 and 89 years, who presented to a single institution with acute urinary retention were studied. A PSA assay was performed on admission and a record made of the prostatic size as assessed by digital rectal examination. All patients underwent a trial without catheter, those that failed to void underwent prostatic surgery whilst all others were followed up as outpatients. RESULTS: Five patients were found to have prostatic carcinoma, three following transurethral resection of the prostate (TURP) and two following needle biopsy, performed because of persistent elevation of the PSA. A significant elevation in the PSA was associated with acute urinary retention, with only 15 (28%) patients having a PSA of 4.0 ng/ml or less. This elevation reduced the sensitivity of PSA in detecting carcinoma of the prostate; even with a cut-off of 20 ng/ml, the positive predictive value of the test was only 21%. CONCLUSIONS: A PSA assay should not be performed at the time of presentation with acute urinary retention as it may lead to unnecessary investigations and anxiety for the patient. For those in whom a PSA assay is desirable a delay of 2 weeks should be allowed prior to sampling, as the half-life of PSA is known to be 2-3 days.

Y-chromosomal DNA haplotypes in infertile European males carrying Y-microdeletions.

We have determined Y-chromosomal DNA haplotypes in 73 infertile European males carrying Y microdeletions and compared them with the haplotypes of 299 infertile males lacking microdeletions. Chromosomes were typed with a set of 11 binary Y markers, which identified 8 haplogroups in the sample. Haplogroup frequencies were compared between 3 microdeletion classes and the non-deleted infertile males. Deletions arise on many different haplotypic backgrounds. No statistically significant differences in frequency were seen, although the small number of AZFa deletions lay predominantly on one branch of the Y haplotype tree.

Genetically determined male infertility and assisted reproduction techniques.

This is a review of the common chromosome and genetic disorders associated with male infertility that need to be considered by the clinician and the couple in the context of treatment. Until recently the most relevant disorders have been those inherited from parents, however, with the advent of technologies enabling recovery of sperm from the testicle in men with severely damaged spermatogenesis there is increased interest in those genetic abnormalities that may occur in mitosis and meioses. It is likely that over the next ten years there will be increasing focus on this aspect of male fertility genetic disorders. This article needs to be read in conjunction with the specific in depth reviews in this journal edition.

Genetics and male infertility.

This article reviews chromosomal and genetic disorders in the context of male fertility. Particular emphasis is on those disorders, which are encountered, in clinical practice including Klinefelter's syndrome, Kallman's syndrome, Androgen insensitivity, Y microdeletions, Y fertility gene deletions, and cystic fibrosis gene mutations. These disorders are discussed in relation to the aetiology of male fertility and also risks to children who are born of fathers with these disorders. A list of fathers' categories is proposed for outcome studies for children born after IVF-ICSI. Finally a question is proposed to catalyse debate about germ line therapy.

Day-case local anaesthetic radiofrequency thermal ablation of benign prostatic hyperplasia: a four-year follow-up.

OBJECTIVE: This study reports long-term (median 4 years) clinical effectiveness, safety and patient acceptance of transurethral ablation prostatectomy (TURAPY) for symptomatic benign prostatic enlargement (BPE) using a radiofrequency technique. MATERIAL AND METHODS: 25 men were treated as day-case procedures under local anaesthesia for 1 h. The age range was 55-88 years (mean age 65.5 years) and all were suffering from symptomatic BPE with urinary flow rates of 12 ml/s or less. The treatment was carried out with a computer-based device using a special heating element mounted on a Foley-like catheter for prostatic ablation and the temperatures were monitored continuously in the prostatic region, sphincteric area and rectum for safety purposes. RESULTS: TURAPY was carried out in all patients with temperatures ranging from 70 to 82 degrees C depending on the tolerance of the patient. The post-treatment mortality was nil and only 19 patients complained of mild dysuria, passing of some debris and/or minor bleeding on voiding which settled spontaneously in 2-3 weeks, except in two patients who had proven urinary infection requiring antibiotic therapy. At 4 years the International Prostate Symptom Score (I-PSS) improved from a mean value of 16.0 to 7.2 (p < 0.01) with quality-of-life score falling from 4 to 1.9 (p < 0.05); mean flow rate increased from 8.5 to 11.7 ml/s and mean residual volume decreased from 185.04 to 52.8 ml (p < 0.05). Post-treatment pressure flow studies in 14 patients showed normal pressure voiding in one, with four being in an equivocal range, but the rest were obstructed. Prostate ultrasound scanning before and after treatment in 15 patients showed a mean reduction of volume of 16.7 ml suggesting cavitation of prostate following TURAPY. CONCLUSIONS: TURAPY provides lasting subjective but modest objective benefits in symptomatic BPE patients. It is worthy of consideration in elderly patients, or in those who are unfit for surgery or who do not wish to undergo surgery. It is a safe procedure with little transient morbidity but no mortality.

Genetic basis of male fertility.

We are in the age of genetic discovery. Now the human genome has been completely sequenced1, there will be increasing understanding and ability to manipulate biochemical pathways downstream of genes. At the same time, further development of in vitro fertilization (IVF) and intracytoplasmic sperm injection(ICSI) will enable procreation in situations that were formerly impossible and when there may be an increased possibility of genetic abnormality. Furthermore, preimplantation diagnosis will enable defects to be diagnosed and will give the opportunity for the couple to decide whether to continue with treatment towards a pregnancy or not. Thus, there is a need for clinicians to have a good knowledge of the gentics and hereditary aspects of male (and indeed female) infertility and for couples to have access to correct information and expert counselling. Also, there are ethical implications of these scientific and clinical advances for the future child, the individual, the couple and society. There is increasing public unease about this new science of reproduction and, in the UK, there is regulation by law; thus, there is a need for clinicians and scientists to give accurate information in everday language to the public.

Changes of serum prostate-specific antigen following high energy thick loop prostatectomy.

We evaluated the effect of the high electrocuting energy used with the thick loop, in transurethral vaporization resection of the prostate (TUVRP), on serum prostate-specific antigen (PSA). Forty-eight patients with benign protatic hyperplasia (BPH) were included in this prospective single arm sequential study. All patients had TUVRP using the 'Wing' thick resection electrode (Richard Wolf, Germany). Serum PSA was measured before, 1 day and 6 weeks in the morning post TUVRP. PSA values were correlated to preoperative prostate size and to prostatic resection weight. Serum PSA values (mean +/- SD) were 6.29+/-4.4 ng/ml, 14.9+/-11.1 and 2.3+/-1.9 before, 1 day and 6 weeks post TUVRP respectively. The mean increase in the PSA at 1 day over baseline value was 2.72, this was statistically significant (p < or = 0.0001). The PSA level returned to less than pre TUVRP value in all but 3 patients by 6 weeks. The PSA value 1 day post TUVRP correlated well with the pre PSA level, prostate size and prostatic resection weight (r = 0.58, r = 0.38 and r = 0.44 respectively) however, the PSA level at 6 weeks correlated only to pre TUVRP values (r = 0.53). We conclude that that serum PSA is not reliable within 6 weeks of TUVRP. The reversible increase in serum PSA value is similar to other forms of prostatectomy which, suggests that the increased level of electrosurgical energy that is used in TUVRP does not have an added adverse effect on the PSA levels.