Should Finasteride Be Routinely Given Preoperatively for TURP?

Objective. The aim of the review was to compare the use of finasteride to placebo in patients undergoing TURP procedures. Material & Methods. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966-November 2011), EMBASE (1980-November 2011), CINAHL, Clinicaltrials.gov, Google Scholar, reference lists of articles, and abstracts from conference proceedings without language restriction for studies comparing finasteride to placebo patients needing TURPs. Results. Four randomised controlled trials were included comparing finasteride to a placebo. A meta-analysis was not conducted due to the disparity present in the results between the studies. Three of the studies found that finasteride could reduce either intra- or postoperative bleeding after TURP. One study found finasteride to significantly lower the microvessel density (MVD) and vascular endothelial growth factor (VEGF). None of the studies reported any long-term complications related to either the medication or the procedure. Conclusion. finasteride reduces bleeding either during or after TURP.

Fluorescence in-situ hybridisation on biopsies from clam ileocystoplasties and on a clam cancer.

The incidence of carcinoma following an enterocystoplasty increases with time and is a major concern after such procedures. The aim of this study was to investigate genetic instability (in the form of numerical chromosomal aberrations) at the enterovesical anastomosis in patients who had undergone a clam ileocystoplasty using fluorescent in-situ hybridisation (FISH). Fluorescent in-situ hybridisation was performed on touch preparation samples prepared from fresh endoscopic biopsies obtained from the enterovesical anastomosis and native bladder remnant (control specimens) of 15 patients who had undergone a clam ileocystoplasty. Fluorescent in-situ hybridisation was also performed on one squamous cell cancer specimen. Significant aneusomic changes were found at the enterovesical anastomosis in all 15 patients. Alterations in chromosome 18 copy number were the most frequent abnormal finding (trisomy 18, n=8; monosomy 18, n=7). Nine patients were monosomic for chromosome 9. Isolated monosomy 8 and trisomy 8 were each found in one patient. The control specimens were all normal. An unusually high incidence of polysomic cells was found in the clam tumour specimen, reflecting the aggressive nature of this cancer. Chromosomal numerical abnormalities occur at the enterovesical anastomosis following a clam ileocystoplasty and chromosome 18 appears to be a particularly good marker of genetic instability. The results of this study indicate that morphologically normal tissue obtained from the enterovesical anastomosis displays evidence of chromosomal instability that may predispose to tumour formation. However, further prospective, blinded, longitudinal studies are required to establish whether predetermined FISH signal patterns in enterocystoplasty cells in urine or obtained by biopsy predict the presence or absence of tumour.

Hepatocyte growth factor/scatter factor and prostate cancer: a review.

Men who die from prostate cancer do so from uncontrolled metastatic disease. A better understanding of the mechanisms involved in the progression and metastasis of prostate cancer may lead to novel therapeutic approaches to prevent its natural progression. Hepatocyte Growth Factor / Scatter factor (HGF/SF) has been demonstrated to elicit a number of key functions in numerous tissues that are important in the progression, invasion and metastasis of cancer. Studies have demonstrated that the activity of HGF/SF and its receptor c-Met are linked to disease progression in numerous cancers. However, research into these functions, which include activities as a mitogen, a motogen and an anti-apoptotic and angiogenic factor in prostate cancer are limited. This article reviews the published evidence of the roles HGF/SF plays in prostate cancer progression and highlights the clinical and therapeutic potential of research into this pleiomorphic cytokine.

Analysis of the prognostic implications of different tumour margin types in renal cell carcinoma.

AIMS: Invasion of perinephric tissues is part of the Union Internationale Contre le Cancer (UICC) (1997) T staging criteria for renal cell carcinoma (RCC) and appears to confer a worse prognosis. However, there are no established histological criteria to determine if this has occurred and histopathologists differ in their interpretation of the tumour margin. The purpose of this study was to determine histological criteria for invasion of perinephric tissues that may be used in staging. METHODS AND RESULTS: We assessed the prognostic implications of different margin types in 176 cases of RCC with good follow-up data. The tumour margin type in each cases was classified as follows: fibrous tumour capsule; rim of kidney; fibrous capsule with 'collar stud' invasion; pushing margin, no capsule; and tumour cell invasion of fat. The margin types were used in univariate and multivariate survival analysis to determine which had most impact on disease-free survival. In Cox regression analysis with all other influential covariates cellular invasion of fat was the only margin type that had any prognostic impact, conferring a 2.9 relative hazard compared with tumours with a fibrous capsule (P = 0.007). CONCLUSIONS: For staging purposes the designation of a tumour as invading perinephric tissues should be limited to those cases that have tumour cells invading the perinephric fat.

Contribution of grade, vascular invasion and age to outcome in clinically localized renal cell carcinoma.

OBJECTIVE: To determine the relative prognostic importance of microvascular invasion in apparently localized renal cell carcinoma (RCC). PATIENTS AND METHODS: A retrospective clinical and pathological review was conducted of 176 consecutive patients identified from pathology records who had a nephrectomy for RCC with a median follow-up of 44 months. Vascular invasion was recorded and categorized by the level of microvascular invasion (MVI), renal vein invasion (RVI) and inferior vena cava invasion (IVCI). Tumour type, grade and size were also assessed. These variables were assessed by univariate and multivariate analysis to determine their effect on disease-free survival. RESULTS: In the univariate analysis tumour size, grade, vascular invasion and young age each predicted reduced disease-free survival. On multivariate analysis for all 176 patients, grade, vascular invasion and young age were the significant independent predictors of reduced disease-free survival. In a subgroup of 149 patients from whom those with very high risk determinants were excluded (those with grade 4 tumours and/or IVCI) most of the risk of metastasis could be accounted for by vascular invasion and young age alone (MVI vs no vascular invasion, hazard ratio 3.18, 95% confidence interval 1.29-7.84; RVI vs no vascular invasion 2.41, 0.989-5.89; and age per year 0.963, 0.94-0.992). CONCLUSIONS: Grade, vascular invasion and young age are the main independent predictors of relapse in clinically localized RCC after nephrectomy. For most patients, who do not have very high risk indicators, the main adverse predictors are vascular invasion and young age. These findings are important when selecting patients for trials of adjuvant therapy and have implications for pathological staging.

Venous thromboembolic prophylaxis for transurethral prostatectomy: practice among British urologists.

Venous thromboembolism (VTE) is an occasional cause of death after transurethral prostatectomy but there are no established guidelines for its prevention in relation to this operation. We assessed practice in the UK by mailing a questionnaire to 460 consultant members of the British Association of Urological Surgeons. 362 (79%) completed questionnaires were received. 280 of 362 (77%) respondents routinely used VTE prophylaxis with transurethral prostatectomy; 82 (23%) did not. 230 of the 280 urologists who took precautions used mechanical methods; 50 used low dose heparin, either with stockings or alone. This survey indicates that, despite a lack of clear evidence, most British urologists favour some form of precaution against VTE in patients undergoing transurethral prostatectomy.

The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer.

Sex hormones appear to play a pivotal role in determining cardiovascular risk. Androgen deprivation therapy for males with prostate cancer results in a hypogonadal state that may have important, but as yet undetermined, effects on the vasculature. We studied the effects of androgen deprivation therapy on large artery stiffness in 22 prostate cancer patients (mean age, 67 +/- 8 yr) over a 6-month period. Arterial stiffness was assessed using pulse-wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and the augmentation index, a measure of large artery stiffness. Body compositional changes were assessed using bioelectrical impedance analysis. Fasting lipids, glucose, insulin, testosterone, and estradiol were measured. After a 3-month treatment period, the augmentation index increased from 24 +/- 6% (mean +/- SD) at baseline to 29 +/- 9% (P = 0.003) despite no change in peripheral blood pressure. Timing of wave reflection was reduced from 137 +/- 7 to 129 +/- 10 msec (P = 0.003). Fat mass increased from 20.2 +/- 9.4 to 21.9 +/- 9.6 kg (P = 0.008), whereas lean body mass decreased from 63.2 +/- 6.8 to 61.5 +/- 6.0 kg (P = 0.016). There were no changes in lipids or glucose during treatment. Median serum insulin rose from 11.8 (range, 5.6-49.1) to 15.1 (range, 7.3-83.2) mU/liter at 1 month (P = 0.021) and to 19.3 (range, 0-85.0 mU/liter by 3 months (P = 0.020). There was a correlation between the changes in fat mass and insulin concentration over the 3-month period (r = 0.56; P = 0.013). In a subgroup of patients whose treatment was discontinued after 3 months, the augmentation index decreased from 31 +/- 7% at 3 months to 29 +/- 5% by 6 months, in contrast to patients receiving continuing treatment in whom the augmentation index remained elevated at 6 months compared with baseline (P = 0.043). These data indicate that induced hypogonadism in males with prostate cancer results in a rise in the augmentation of central arterial pressure, suggesting large artery stiffening. Adverse body compositional changes associated with rising insulin concentrations suggest reduced insulin sensitivity. These adverse hemodynamic and metabolic effects may increase cardiovascular risk in this patient group.

Somatostatin analogs in oncology: a look to the future.

In the past 15 years considerable advances have been made in our understanding of the molecular pharmacology of the mechanisms whereby somatostatin and its analogs mediate their direct and indirect antineoplastic effects. However, some important issues remain to be resolved, in particular the functional roles of the individual somatostatin receptors (SSTR-1-5) in tumor tissue and up- or downregulation of the hSSTRs with prolonged administration of somatostatin analogs. Answers to these questions are essential before we can maximize the therapeutic efficacy of somatostatin analogs in cancer. For example, is continuous administration more or less effective than intermittent therapy? The role of somatostatin analogs in the management of acromegaly and to a lesser extent neuroendocrine tumors is firmly established. The development of depot preparations of all 3 somatostatin analogs currently available for clinical use will undoubtedly improve both patient compliance and quality of life in patients with these conditions. There are only likely to be minor differences in the therapeutic efficacy of octreotide, lanreotide and vapreotide since all three analogs exert the majority of their antineoplastic effects via hSSTR-2 and hSSTR-5 and at the end of the day, price may well dictate which of these drugs oncologists use to provide symptomatic palliation of acromegaly and neuroendocrine tumors. Apart from some notable exceptions, somatostatin analog therapy has proven to be very disappointing in the management of advanced malignancy. Improvements in the management of solid tumors are likely to come only from combination therapy of somatostatin analogs with cytotoxic agents or other hormones in both advanced malignancy and in the adjuvant setting. Clinical trials with clear-cut objective outcome measures and health-related quality of life assessment are needed to evaluate the therapeutic efficacy of combination treatment in advanced malignancy and as an adjuvant to surgery. Particular attention needs to be paid to possible adverse effects of somatostatin analog therapy on the immune response to cancer. Further studies are required to establish whether the adverse effects of somatostatin analog therapy alone or in combination with cytotoxics or other hormones can be reversed with appropriate immunomodulatory treatment. Targeted somatostatin analog radiotherapy and chemotherapy are currently being investigated and the results of these studies are awaited with interest. Novel approaches using combinations of somatostatin analogs with antiangiogenic drugs or gene therapy are of particular interest and may provide important advances in the management of cancer in the not too distant future.

Role of transurethral biopsy sampling of the prostate to diagnose prostate cancer in men undergoing surgical intervention for benign prostatic hyperplasia.

PURPOSE: Newer minimally invasive surgical procedures are being used to treat men with significant benign prostatic hyperplasia (BPH). These modalities do not allow retrieval of prostate tissue for histologic review. The goal of our study was to assess the value of transurethral biopsies in detecting prostate cancer in men who would undergo surgical intervention for BPH. MATERIALS AND METHODS: Between September 1997 and January 1999, 422 men undergoing transurethral resection of the prostate (TURP) had transurethral biopsies obtained before completing the TURP. Pathology reports as well as prostate-specific antigen (PSA) results were reviewed and analyzed to determine when cancer was present. RESULTS: Pathological examination revealed that cancer was found in 53 men (12.5%). The transurethral biopsies detected cancer in 32 of 53 (60.4%). No cancers were found in the transurethral biopsy specimen only. Of the 21 cancers missed by transurethral biopsy, 7 were stage T1b. PSA level >10 ng/mL increased the likelihood of finding cancer. CONCLUSIONS: Transurethral biopsy sampling is unreliable for detecting prostate cancer in men with clinically significant BPH. Significant cancers are missed if transurethral biopsies are used to determine the presence of carcinoma before minimally invasive surgical therapy for BPH.

Hepatosplanchnic haemodynamics and renal blood flow and function in rats with liver failure.

BACKGROUND: Massive liver necrosis, characteristic of acute liver failure, may affect hepatosplanchnic haemodynamics, and contribute to the alterations in renal haemodynamics and function. AIMS: To investigate the relation between hepatosplanchnic haemodynamics, including portal systemic shunting, and renal blood flow and function in rats with acute liver failure. METHODS: Liver failure was induced in male Wistar rats by intraperitoneal injection of 1.1 g/kg of D(+)-galactosamine hydrochloride. The parameters assessed included; systemic, hepatosplanchnic, and renal blood flow (57Co microsphere method); portal-systemic shunting and intrarenal shunting (consecutive intrasplenic, intraportal, or renal arterial injections of 99mTc methylene diphosphonate and 99mTc albumin microspheres); arterial blood pressure and portal pressure; renal function; and liver function (liver function tests and 14C aminopyrine breath test). RESULTS: Progressive liver dysfunction was accompanied by the development of a hyperdynamic circulation, a highly significant decrease in renal blood flow and function, and an increase in intrarenal shunting 36, 42, and 48 hours after administration of D-galactosamine. The alterations in renal blood flow and function were accompanied by significant increases in portal pressure, portal venous inflow, and intrahepatic portal systemic shunting in galactosamine treated rats compared with controls. There was a significant correlation between changes in renal blood flow and changes in portal pressure, intrahepatic portal systemic shunting, and deterioration in liver function (r = 0.8, p < 0.0001). CONCLUSIONS: The results of this study suggest that both increased intrahepatic portal systemic shunting and hepatocyte impairment may contribute to alterations in renal haemodynamics and function.

Substitution cystoplasty for intractable interstitial cystitis.

OBJECTIVE: To assess the results of substitution cystoplasty for the treatment of intractable interstitial cystitis (IC). PATIENTS AND METHODS: Thirty-two patients (29 women and three men; mean age 58 years, range 24-74) with intractable IC resistant to conservative therapy who had undergone substitution cystoplasty between 1983 and 1992 were reviewed. Their bladder capacities were measured pre-operatively and related to the outcome of treatment. RESULTS: All but two of the 22 women with a bladder capacity of < 250 mL under anaesthetic were improved (five) or cured (15) of their symptoms. The results in women with larger bladder capacities were much less reliable, with only two of seven being cured of their symptoms. The three men all had a good result. Those who had undergone supratrigonal cystectomy were more likely to void spontaneously, but four patients developed pyelonephritis from associated reflux. Subtotal cystectomy reduced the likelihood of reflux and, although there were too few patients for statistical significance, probably increased the chance of cure at the expense of increasing the need for intermittent self-catheterization (ISC). CONCLUSIONS: Pre-operative bladder capacity under anaesthetic is the most reliable predictor of outcome of substitution cystoplasty for treating intractable IC in women. It is contra-indicated if bladder capacity is > 250 mL. Supratrigonal cystectomy is a quick and easy operation and is preferable in the older patient. Subtotal cystectomy with reimplantation of the ureters is preferable in the younger patient, even though it may increase the need for ISC.

Radiotherapy for palliation of locally advanced prostatic carcinoma.

Some patients present with distressing symptoms due to locally advanced prostatic carcinoma which may be refractory to hormonal manipulation and/or surgical treatment. Over an 8-year period 26 patients received local palliative radiotherapy for recurrent bleeding and lower urinary outflow tract obstruction. All were treated with conventional external beam radiotherapy and all but 2 obtained useful palliation of symptoms, especially those with recurrent bleeding. We also found that radiotherapy could be given to the majority of patients on an out-patient basis in 2 or 3 fractions. This was well tolerated and there were few side effects.

Changes in seminal quality following oral zinc therapy.

33 subfertile men with idiopathic asthenozoospermia and/or oligozoospermia were treated with oral zinc sulphate. After treatment a significant improvement in the percentage progressive and total sperm motility was noted accompanied by a significant increase in seminal fluid zinc levels.