A pain in the neck -- an unexpected complication of transrectal ultrasound and biopsy.

In the UK, over 26 000 cases of prostate cancer are diagnosed annually, with many more patients undergoing investigation. Prostate-specific antigen (PSA) testing and its interpretation has always been controversial. Many patients undergo PSA-driven biopsies, which can cause significant morbidity. We report an unusual but severe complication following transrectal ultrasound and biopsy.

Gyrus bipolar electrovaporization vs transurethral resection of the prostate: a randomized prospective single-blind trial with 1 y follow-up.

The Gyrus system uses bipolar electrocautery with saline irrigation to vaporize prostatic tissue and is compared to transurethral resection of the prostate (TURP) in a randomized prospective study with 1 y follow-up. Outcomes measured were fluid absorption, blood loss, period of catheterization, hospital stay, symptom scores, quality of life, flow rates, and post-void residual volumes at 3, 6, and 12 months. All measured parameters were similar, although re-catheterization rates were higher (30% vs 5%) in the Gyrus group. Clot evacuation rates were higher in the TURP group (19% vs 0%). The Gyrus device is safe and produces results that are similar to TURP at 1 y.

Molecular markers for predicting prostate cancer stage and survival.

OBJECTIVE: To assess several molecular markers (detected by immunohistochemistry, IHC) to determine whether they can be used to improve the prognostic value of histological grade alone in predicting the behaviour of prostate cancer. PATIENTS AND METHODS: Tumour tissue was retrieved from 156 men in whom tumour grade, stage and survival were known. The outcome measures were: (i) local stage (T-stage, organ-confined vs extraprostatic); (ii) metastatic status (M-stage, bone metastasis vs no bone metastasis); and (iii) survival. The IHC markers used were chosen to provide a broad representation of various aspects of tumour biology, i.e. the androgen receptor (AR) and oestrogen receptor (ER), adhesion molecules (E-cadherin), proliferation markers (MIB-1), tumour-suppressor genes (TP53 and the retinoblastoma gene product, Rb) and other novel cancer-related proteins (cyclin D1 and the breast cancer susceptibility gene product, BRCA2). All factors were assessed using logistic regression and Cox proportional-hazards survival models for predictive value, after adjusting for effects. RESULTS: MIB-1, ER, cyclin D1 and E-cadherin all showed close statistically significant univariate associations with histological grade. Univariate analysis also identified close statistically significant associations between T-stage and both MIB-1 and E-cadherin. Likewise, there were close univariate associations for both M-stage and survival, and MIB-1, cyclin D1 and ER. Logistic regression modelling identified MIB-1, cyclin D1 and ER as statistically significant predictors of M-stage and, once MIB-1 was entered into the model, the effects of grade no longer made a significant contribution. MIB-1 was a significant predictor for T-stage, but the effects of grade remained significant in this model. Cox proportional-hazards modelling identified MIB-1, cyclin D1 and ER as being statistically significant predictors of survival, after adjusting for grade. After adjusting for both grade and MIB-1, the effects of cyclin D1 and ER were no longer statistically significant. Excess MIB-1, cyclin D1 or ER expression tended to be present within the most poorly differentiated and advanced-stage lesions; this provides an inherent instability to the models described. TP53, Rb, AR and BRCA2 were of limited prognostic value. CONCLUSIONS: MIB-1, ER and cyclin D1 provide prognostic information that is clearly independent of grade. However, their true clinical value is probably limited because they are expressed mainly in the most advanced lesions. Nevertheless, MIB-1 expression is of sufficient value to warrant inclusion in future prognostic models. Furthermore, the expression of cyclin D1 and ER may reflect aspects of tumour biology that individually are worthy of further investigation. However, none of the IHC markers used in this study can be recommended for use in routine histological preparations.

The frequency of germ-line mutations in the breast cancer predisposition genes BRCA1 and BRCA2 in familial prostate cancer. The Cancer Research Campaign/British Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators.

Predisposition to prostate cancer has a genetic component, and there are reports of familial clustering of breast and prostate cancer. Two highly penetrant genes that predispose individuals to breast cancer (BRCA1 and BRCA2) are known to confer an increased risk of prostate cancer of about 3-fold and 7-fold, respectively, in breast cancer families. Blood DNA from affected individuals in 38 prostate cancer clusters was analyzed for germ-line mutations in BRCA1 and BRCA2 to assess the contribution of each of these genes to familial prostate cancer. Seventeen DNA samples were each from an affected individual in families with three or more cases of prostate cancer at any age; 20 samples were from one of affected sibling pairs where one was < or = 67 years at diagnosis. No germ-line mutations were found in BRCA1. Two germ-line mutations in BRCA2 were found, and both were seen in individuals whose age at diagnosis was very young (< or = 56 years) and who were members of an affected sibling pair. One is a 4-bp deletion at base 6710 (exon 11) in a man who had prostate cancer at 54 years, and the other is a 2-bp deletion at base 5531 (exon 11) in a man who had prostate cancer at 56 years. In both cases, the wild-type allele was lost in the patient's prostate tumor at the BRCA2 locus. However, intriguingly, in neither case did the affected brother also carry the mutation. Germ-line mutations in BRCA2 may therefore account for about 5% of prostate cancer in familial clusters.

Allelic imbalance in familial and sporadic prostate cancer at the putative human prostate cancer susceptibility locus, HPC1. CRC/BPG UK Familial Prostate Cancer Study Collaborators. Cancer Research Campaign/British Prostate Group.

A recent report has provided strong evidence for a major prostate cancer susceptibility locus (HPC1) on chromosome 1q24-25 (Smith et al, 1996). Most inherited cancer susceptibility genes function as tumour-suppressor genes (TSGs). Allelic loss or imbalance in tumour tissue is often the hallmark of a TSG. Studies of allelic loss have not previously implicated the chromosomal region 1q24-25 in prostate cancer. However, analysis of tumour DNA from cases in prostate cancer families has not been reported. In this study, we have evaluated DNA from tissue obtained from small families [3-5 affected members (n = 17)], sibling pairs (n = 15) and sporadic (n = 40) prostate tumours using the three markers from Smith et al (1996) that defined the maximum multipoint linkage lod score. Although widely spaced (12-50 cM), each marker showed evidence of allelic imbalance in only approximately 7.5% of informative tumours. There was no difference between the familial and sporadic cases. We conclude that the incidence of allelic imbalance at HPC1 is low in both sporadic tumours and small prostate cancer families. In this group of patients, HPC1 is unlikely to be acting as a TSG in the development of prostate cancer.

Immunotherapy of advanced prostate cancer: a phase I/II trial using Mycobacterium vaccae (SRL172).

OBJECTIVE: To assess whether a new heat-killed Mycobacterium vaccae preparation (SRL172), which enhances cell-mediated immunity and has been proposed for use as an immunotherapeutic agent against cancer, is safe in patients with advanced hormone-refractory prostate cancer, can stimulate desirable cytokine changes in these patients and modulate the progression of the disease. PATIENTS AND METHODS: Ten patients were given SRL172 intradermally at regular intervals. The serum prostate specific antigen (PSA) level was used as a surrogate marker of response. The proportion of peripheral blood mononuclear cells (PBMC) secreting interleukin 2 (IL2), interferon gamma (IFNgamma) and interleukin 4 (IL4) was measured by flow cytometry (FACS) before and after vaccination to assess whether the treatment induced a Th2 (predominantly humoral) to Th1 (predominantly cell-mediated) switch. RESULTS: There were no significant adverse events. In five patients the serum PSA declined during the trial and in two of these there was no concomitant change of therapy apart from vaccination with SRL172. Before vaccination with SRL172 patients had a low proportion of PBMC producing IFNgamma and IL2 (all 10) and a higher proportion secreting IL4 (all three tested), suggesting a predominantly Th2 cytokine profile. After vaccination the proportion of IL4 secreting PBMC fell in all three patients tested. The proportion of IL2 secreting PBMC increased in three patients whose PSA fell. The proportion of IFNgamma-secreting cells remained depressed in nine of 10 patients. CONCLUSION: Two patients with advanced hormone-refractory prostate cancer had a PSA response to the vaccination with SRL172. The proportion of PBMC secreting IL2 is a potential marker of response to immunotherapy.

Immunohistochemical expression of BRCA2 protein and allelic loss at the BRCA2 locus in prostate cancer. CRC/BPG UK Familial Prostate Cancer Study Collaborators.

Many epidemiological studies have reported an association between breast and prostate cancer. BRCA2 functions as a tumour-suppressor gene in about 35% of large familial breast-cancer clusters; its role in the pathogenesis of sporadic breast cancer is less clear. We have evaluated immunohistochemical expression of BRCA2 protein and allelic loss of markers at the BRCA2 locus in tissue derived both from sporadic and from familial cases of prostate cancer. Immunohistochemical analysis was performed in 167 paraffin-embedded archival specimens. Normal prostate and 75% (120/160) of prostate-cancer tissue did not express BRCA2 protein. However, 25% (40/160) of cancer cases did express patchy staining; of these, 17% (2711 60) expressed positive nuclear staining in normal glandular tissue adjacent to tumour (either in addition to, or, independent of tumour). Allelic loss is the hallmark of a tumour-suppressor gene. Markers flanking (D13S267, D13S260) and within (D13S171) the BRCA2 gene indicated allelic loss in at least one locus in 23% (17/73) of tumours analyzed. There was no difference in the rates of allelic loss between sporadic and familial tumours, nor was there any association between immunohistochemical staining and allelic loss. Although immunohistochemical staining provided no useful prognostic information, allelic loss at BRCA2 was shown in univariate analysis to be associated with poorer survival (log-rank test, p = 0.046).

Francois de LaPeyronie (1978-1747): the man and the disease he described.

The evaluation of the treatments for Peyronie's disease is difficult; the natural history is such that the plaque may resolve spontaneously [82]. In 1973, Alec Badenoch made this comment and noted that no treatment had then been evaluated in a controlled clinical study [83]. The origin of the eponym is vague and the disease remains an enigma. To this day, the treatment can be difficult. It is not surprising that so many treatments have been tried and so much dogma written. Indeed, in 1903, William Johnson Walsham, the famous surgeon from St Bartholomew's Hospital in London, and author of the standard surgical text book of the day, wrote; "... if treatment of the plaque with iodides is unsuccessful ... or if the induration progresses ... then the whole penis must be promptly amputated!' [44]. We no longer believe this dictuml.

The aetiology and management of erectile, ejaculatory, and fertility problems in men with diabetes mellitus.

Erectile impotence is more common in the diabetic than the general population, occurs at a younger age, and is often associated with ejaculatory problems. For these, and possibly for other more subtle reasons, fertility may be a problem for men with diabetes. The symptoms of erectile and ejaculatory dysfunction are frequently not discussed between patient and doctor. Psychological factors are important but the vast majority of diabetic patients have an organic basis for their impotence. Both neurogenic and vascular factors are important in the pathogenesis of erectile failure. Autonomic neuropathy is almost certainly the cause of the ejaculatory failure that may be present in up to 40% of men with diabetes. The final biochemical mediator of erection within the penile erectile tissue is nitric oxide and a key enzyme in its degradation is phosphodiesterase (type V). Drugs that affect the metabolism of this enzyme are being developed to treat erectile failure. At present, the self injection of intra-cavernosal erectogenic agents (such as prostaglandin E1) provide the main form of therapy for erectile failure. Vacuum devices are a simple alternative and venous ligation surgery may be effective for a properly selected cohort of patients. Prosthetic implants are a final option for patients in whom all else has failed. Fertility problems, particularly when associated with ejaculatory failure can be overcome with modern assisted reproductive techniques. Nowadays, these will frequently involve gamete micro-manipulation.

Reproducibility of uroflow measurement: experience during a double-blind, placebo-controlled study of doxazosin in benign prostatic hyperplasia.

OBJECTIVES: To evaluate the interindividual and intraindividual variation of uroflow measurements in men with benign prostatic hyperplasia (BPH). METHODS: A total of 147 men with clinical evidence of BPH underwent two uroflow measurements at each of two screening visits prior to recruitment into a placebo-controlled study of doxazosin in the treatment of BPH. The maximum and mean flow rates were determined on each occasion. Differences in the mean value of both parameters for the cohort were examined. The intraindividual variability was evaluated using intraclass correlation coefficients and differences in maximum uroflow at each visit were examined. RESULTS: Uroflow measurements for the cohort were reproducible and there was no clinically significant difference in maximum and mean flow rate on each occasion. However, the intraclass correlation coefficients for the mean and maximum flow rate varied between 0.70 and 0.82, indicating that intraindividual variation accounted for a substantial component of the total variation in uroflow observed among these patients. For many individuals, test-retest differences were clinically relevant. CONCLUSIONS: For a group of patients, maximum and mean uroflow measurements are reproducible. However, for an individual, these parameters are subject to clinically significant variation and a single measurement may not be representative. This may be important when considering the need for therapeutic intervention.

The day-to-day variation (test-retest reliability) of residual urine measurement.

OBJECTIVE: To determine the variation in repeated measurements of post-void residual urine volume (PVR), determined by transabdominal ultrasonography (TAUS), within an individual over time (test-retest reliability). PATIENTS AND METHODS: Forty men with symptomatic benign prostatic hyperplasia and awaiting transurethral resection of the prostate were studied over 3 months. Each underwent TAUS to determine both pre- and post-micturition residual volumes on six occasions within the study period. RESULTS: Although one-third of the patients had approximately constant residual volumes (variation in range < 120 mL), two-thirds had wide intra-individual variations over time (variation in range 150-670 mL). The values were log transformed to give a normal distribution and subjected to analysis of variance; there was a wide variation between and also within individuals. The larger the mean PVR, the larger was the overall variation in time. For those with a mean PVR of < 100 mL, the variation was less marked and these patients showed a more consistent test-retest repeatability. CONCLUSIONS: Although the PVR determined by TAUS may be useful to indicate aspects of bladder dysfunction or outlet obstruction, the wide variation in repeated measurements in the same individual limits its use for any clinical purpose that requires repeated assessment, e.g. in monitoring the response to treatment. There is poor test-retest reliability and PVRs cannot be determined reliably from a single measurement.