Single photon emission computerized tomography with capromab pendetide plus computerized tomography image set co-registration independently predicts biochemical failure.

PURPOSE: We evaluate the usefulness of pretreatment (111)Indium capromab pendetide (ProstaScint) planar imaging (immunoscintigraphy) plus single photon emission tomography co-registration with computerized tomography scans to detect occult metastatic disease and predict for biochemical failure, in a cohort of patients with a clinical diagnosis of localized adenocarcinoma of the prostate referred for primary radiotherapy. MATERIALS AND METHODS: Patients were followed after radiotherapy for evidence of biochemical failure using 2 criteria of prostate specific antigen clinical nadir +2 ng/ml and American Society for Therapeutic Radiology and Oncology Consensus definitions. Median followup was 58.8 months (mean 64.8). Clinical risk factors defined 3 risk groups of high (51), intermediate (72) and low (116). RESULTS: Overall biochemical failure was 18.3% vs 11.8% by the 2-BFC at 8-year actuarial analysis with 58.8 months median followup. By the CN +2 definition the control date for the cohort is 34.8 months. Pretreatment SPECT/CT suggested prostate cancer metastasis (22), seminal vesicle extension (20) and organ confined disease (197). Biochemical failure in patients having extra-periprostatic metastatic prostate cancer, seminal vesicle extension and organ confined disease uptake on SPECT/CT was 43.2%, 16.0% vs 14.7% (p = 0.0006); and 33.3%, 15.0% vs 8.7% (p = 0.0017) by the 2-BFC, respectively. Cox multiple regression analysis demonstrated that a finding of extra-periprostatic metastatic prostate on SPECT/CT significantly predicted a 4.2-fold greater risk (p = 0.0012) and a 4.5-fold greater risk (p = 0.0011) of failure by the 2-BFC than organ confined disease adjusting for treatment and risk group. CONCLUSIONS: Unconfirmed findings of extra-periprostatic metastatic prostate cancer on SPECT/CT immunoscintigraphy independently and significantly predicted an increased risk of biochemical failure in patients presenting for radiotherapy with a clinical diagnosis of localized prostate cancer.

Experimental rodent models of prostatitis: limitations and potential.

Prostatitis is a polyetiological inflammation of the prostate gland in men characterized by pelvic pain, irritative voiding symptoms, and sexual dysfunction. Histologically prostatitis is characterized by poly- and mononuclear cell infiltrates (neutrophils, lymphocytes, macrophages and plasma cells) in the stromal connective tissue around the acini or ducts. Prostatitis is an important worldwide health problem in men. The pathogenesis and diagnostic criteria for the condition are obscure, with the result that the development of management programs for this condition has been hindered. Animal model(s) might be useful in elucidating mechanisms involved in the molecular pathogenesis of chronic nonbacterial prostatitis and chronic pelvic pain syndrome. Given that prostatitis might have a multifactorial etiology, several animal models with unique features may prove helpful. This review examines a number of experimental rodent models of prostatitis and evaluates their advantages and limitations.

Rapid onset of action with alfuzosin 10 mg once daily in men with benign prostatic hyperplasia: a randomized, placebo-controlled trial.

This randomized, double-blind, placebo-controlled study was conducted to investigate whether alfuzosin 10 mg once daily improves the maximum flow rate (Q(max)) and lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) after 1 week and 1 month of treatment. A total of 372 men aged > or = 50 years with symptomatic BPH received alfuzosin or placebo for 28 days. Q(max) increased significantly from baseline at day 8 with alfuzosin (P<0.001 versus placebo); this improvement was evident within 24 h after the first dose and was maintained at day 29. LUTS improved from baseline with alfuzosin at day 8 (P=0.07 versus placebo) and day 29 (P=0.003 versus placebo). Alfuzosin 10 mg once daily exhibits a rapid onset of action, with improvements in Q(max) and LUTS maintained through 1 month of treatment.

What is sexual medicine?

Sexual medicine is unique in that it permeates throughout various medical specialties, without having its own defined borders. Urology, gynecology, primary care, endocrinology and cardiology are connected to sexual medicine to varying degrees. Should sexual medicine be a requisite part of the aforementioned teaching programs? Dr Martin Resnick, Lester Persky Professor and Chairman, Department of Urology, Case Western Reserve University, provides a perspective on this topic.

Prostate cancer and consistency of reporting sexual histories in men over age 50.

We conducted an in-person interview to examine the reliability of reported sexual histories among men over age 50 y with and without prostate cancer. Marriage and cohabitation were used as memory cues to recall sexual activity. High correlations on test-retest for questions evaluating sexual histories suggest reliable answers for most factors, and specifically for age at first sexual activity, and lifetime number of sexual partners. Low correlations were seen for ill-defined and socially undesirable items. These data suggest that men consistently report most measures of sexual activity when using marriage and cohabitation as memory cues to recall sexual histories.

Vasectomy and the risk of prostate cancer: a meta-analysis examining vasectomy status, age at vasectomy, and time since vasectomy.

The aim of this study was to conduct a quantitative review of prostate cancer studies to pool relative risk (RR) estimates on the association between prostate cancer and vasectomy, in an attempt to determine whether there is an association, and if so, its magnitude. Random-effects models were examined along with a linear model for time since vasectomy. The pooled RR estimate was 1.37 (95% CI=1.15-1.62) based on five cohort studies and 17 case-control studies. The RR estimate varied by study design with the lowest risk for population-based case-control studies. No difference was seen in risk by age at vasectomy. A linear trend based on the 16 studies reporting time since vasectomy suggested an 10% increase for each additional 10 y or a RR of 1.32 (95% CI=1.17-1.50) for 30 y since vasectomy. When null effects were assumed for the six studies not reporting information, the linear RR for the 22 studies was 1.07 (1.03-1.11) and 1.23 (1.11-1.37) for 10 and 30 y since vasectomy, respectively. These results suggest that men with a prior vasectomy may be at an increased risk of prostate cancer, however, the increase may not be causal since potential bias cannot be discounted. The overall association was small and therefore could be explained by bias. The latency effect shown here for time since vasectomy should be examined further.

Levels of urinary inter-alpha-trypsin inhibitor trimer as a function of age and sex-hormone status in males and females not forming stones.

OBJECTIVES: To determine if levels of inter-alpha-trypsin inhibitor (I alpha TI)-trimer differ in normal individuals based on age, gender or hormonal status, as the regulation of calcium oxalate (CaOx) crystallization inhibitors, e.g. by sex steroids, could be a mechanism contributing to the differences in CaOx urolithiasis between the sexes. SUBJECTS AND METHODS: Voided urine samples were collected from normal males and females. In Experiment 1 samples were grouped by gender and age, i.e. paediatric (PED) < or = 10 years, male (M) 21, female (F) 14; young adult (YGAD) 20-30 years, M 23, F 18; adults (AD), 35-50 year, M 25, F 13; adults aged > or = 60 years (> 60), M 24, F 16 (totals, M 93, F 61). In Experiment 2 samples were grouped by gender, age and hormonal status, i.e. PED, M 24, F 17; AD, M 24, F 22; > 60 and not on hormonal therapy, M 23, F 30; M > 60 and on androgen deprivation therapy (ANDEP) 18; and F > 60 on oestrogen supplementation, F+EST, 18 (total M 89, F 85). Levels of urinary I alpha TI-trimer were determined by immunoblotting and enhanced chemiluminescence, and relative densities of the bands determined. RESULTS: In both experiments the relative levels of I alpha TI-trimer were 2-7 times higher in M-PED than in all other groups of males (P < or = 0.007). Among adult males, I alpha TI-trimer levels were similar in all groups, including ANDEP (P > or = 0.9). There were no differences in the relative levels of I alpha TI-trimer among any of the groups of females, regardless of age or hormonal status (P > or = 0.7). CONCLUSIONS: In males a decrease in I alpha TI-trimer was associated with the onset of adulthood and entry into the 'stone-forming years'. Females did not show this decrease, and neither sex showed an increase in I alpha TI-trimer in the > 60 group, when the incidence of CaOx urolithiasis is supposedly declining. While changes in urinary I alpha TI-trimer levels in males may reflect maturational changes in the kidney, overall these data do not support the hypothesis that the age-related changes in the incidence of urolithiasis are paralleled by changes in the expression I alpha TI-trimer. Additionally, the sex steroids do not appear to acutely regulate the expression of I alpha TI-trimer in adults, making differences in I alpha TI-trimer levels unlikely to be the reason for the disparity in the incidence of CaOx urolithiasis between the sexes.

The technique of radical perineal prostatectomy.

The resurgence of the radical perineal prostatectomy for the treatment of localized prostate cancer has been facilitated by the current emphasis on reducing medical costs, the identification of more cases of localized disease, the selected use of lymphadenectomy, and the use of laparoscopic techniques to perform node sampling. This technique provides a cost-effective, low-morbidity, and efficacious means of treating localized prostate cancer.

Perfusion-modulated MR imaging-guided radiofrequency ablation of the kidney in a porcine model.

OBJECTIVE: This study was performed to test the hypothesis that temporary renal ischemia will result in increased thermal lesion size during radiofrequency thermal ablation in the kidney. MATERIALS AND METHODS: Twelve kidneys were treated in six pigs that were placed under general anesthesia in the MR suite, using a 0.2-T open C-shaped MR imaging system. A 4-cm-long, 14-mm-diameter balloon catheter was placed into the aorta using a transfemoral approach, and the balloon was positioned proximal to the renal arteries via guidance with MR imaging. A 2-cm exposed-tip MR-compatible 17-gauge radiofrequency electrode was placed into one kidney under MR fluoroscopy using fast imaging with steady-state free precession (FISP) sequences. Thermal ablation was performed with the electrode tip temperature maintained at 90 +/- 2 degrees C for 10 min. This procedure was repeated in the contralateral kidney. The balloon was inflated during one ablation. Postablation images were obtained, the pigs were sacrificed, and both kidneys of each animal were harvested for pathologic correlation. RESULTS: Technical success was achieved in all animals. The lesion measured 14.2 +/- 2.2 mm (mean +/- standard deviation) for the ischemic kidney versus 8.0 +/- 2.6 mm in the normally perfused kidney (p = 0.00002). No significant complications were noted. In all images, thermal lesions displayed low signal intensity with a sharp rim of high signal intensity best visualized using short tau inversion recovery (STIR) sequences with a mean accuracy of 1.3 +/- 1.2 mm when compared with pathologic findings and a mean contrast-to-noise ratio of 4.9 +/- 2.5. CONCLUSION: We accept the hypothesis that temporary renal ischemia leads to a significantly increased radiofrequency ablation lesion size. We conclude that catheter-based balloon perfusion reduction is feasible, that the procedure does not lead to major complications, and that it can be performed using MR imaging as the sole imaging modality.

Urological medical malpractice.

PURPOSE: Like all other medical and surgical practitioners, urologists are occasionally confronted with the unpleasant realization that they are being sued for medical malpractice. These suits are generated through any number of acts or failures to act during innumerable circumstances. We reviewed all urological claims presented to 1 representative insurance company and delineated the types of acts, settings, expenses and disposition of these claims. This review was performed to understand better the claims confronting urologists and provide future guidance to urologists in the medical malpractice setting. METHODS AND MATERIALS: Working with The St. Paul Companies 259 medical malpractice claims against urologists consecutively closed from 1995 to 1999 were reviewed. Claims were defined as urological malpractice when the insured-defendant in a malpractice claim was a urologist. Each claim was reviewed in terms of disposition, patient age, geographic location, office-hospital setting, purported negligent act, procedure if applicable, litigation status and expenses incurred. Data ascertained were then compared to national practice statistics provided by the American Urological Association (AUA) and American Medical Association. In addition, a literature search with the key words urology and malpractice was performed. Related pertinent documents were reviewed and incorporated into this analysis. RESULTS: We reviewed 259 urological medical malpractice claims closed between 1995 and 1999. During this period The St. Paul Companies insured various numbers of private practice urologists. In the years ending 1995 to 1999, 489, 492, 438, 377 and 426 individual urologists, respectively, were insured with respective premiums paid in the amounts of $6.27, $6.23, $5.80, $5.15 and $3.87 million. Claims were analyzed by AUA section. The greatest incidence of claims occurred in the Southeastern section, followed by the North Central, South Central, Mid-Atlantic, New England, Western and New York sections. According to AUA statistics the greatest number of practicing urologists are in the Southeastern section, followed by the Western, North Central, South Central, Mid-Atlantic, New York, New England and Northeastern sections. When analyzing average expenses, the New England section had the most costly claims, followed by the Mid-Atlantic, North Central, Southeastern, South Central, Western and New York sections with respective mean expenses of $266,887, $145,031, $47,667, $41,843, $38,365, $30,037 and $1,065 per claim, respectively. The greatest percent of claims arose from the categories of inpatient, adult and surgical procedures. Endourological procedures resulted in the greatest incidence of surgical claims. However, claims related to prostatectomy involved the most expensive claims with a mean cost of $185,345. Of the surgical procedures incidents defined as postoperative complications were the most common acts of negligence generating a malpractice claim. The majority of malpractice claims were filed in court but subsequently voluntarily dismissed by the plaintiff. CONCLUSIONS: Medical malpractice persists as an issue confronting urologists. Urologists must strive to maintain open, honest, in-depth communications with their patients when occurrences with potential malpractice overtones arise.

Radioimmunoguided imaging of prostate cancer foci with histopathological correlation.

PURPOSE: We have previously presented a technique that fuses ProstaScint and pelvic CT images for the purpose of designing brachytherapy that targets areas at high risk for treatment failure. We now correlate areas of increased intensity seen on ProstaScint-CT fusion images to biopsy results in a series of 7 patients to evaluate the accuracy of this technique in localizing intraprostatic disease. METHODS AND MATERIALS: The 7 patients included in this study were evaluated between June 1998 and March 29, 1999 at Metrohealth Medical Center and University Hospitals of Cleveland in Cleveland, Ohio. ProstaScint and CT scans of each patient were obtained before transperineal biopsy and seed implantation. Each patient's prostate gland was biopsied at 12 separate sites determined independently of Prostascint-CT scan results. RESULTS: When correlated with biopsy results, our method yielded an overall accuracy of 80%: with a sensitivity of 79%, a specificity of 80%, a positive predictive value of 68%, and a negative predictive value of 88%. CONCLUSION: The image fusion of the pelvic CT scan and ProstaScint scan helped identify foci of adenocarcinoma within the prostate that correlated well with biopsy results. These data may be useful to escalate doses in regions containing tumor by either high-dose rate or low-dose rate brachytherapy, as well as by external beam techniques such as intensity modulated radiotherapy (IMRT).

Expression of proteins that inhibit calcium oxalate crystallization in vitro in the urine of normal and stone-forming individuals.

The factors precipitating clinically active calcium oxalate (CaOx) urolithiasis are not known. This study examined the relationships between urinary proteins that inhibit CaOx crystallization in vitro and the incidence of CaOx urolithiasis. The first hypothesis is that levels of urinary CaOx crystallization inhibitors differ between clinically active stone formers (SFs) and normal individuals. The second hypothesis is that lower levels of urinary CaOx crystallization inhibitors contribute to the two- to threefold greater incidence of CaOx urolithiasis in males compared with females. These hypotheses were derived from previous observations on the expression of urinary inter-alpha-trypsin inhibitor trimer (IalphaTI-trimer) in normal and stone-forming individuals. The proteins of void urine samples from normal volunteers (24 males, 19 females) and CaOx-SFs (26 males, 16 females) were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoreactive IalphaTI-trimer, osteopontin, and prothrombin were detected by immunoblot plus enhanced chemiluminescence; the relative densities of the bands were then determined. With the exception of IalphaTI-trimer (P:

Feasibility and acute toxicities of radioimmunoguided prostate brachytherapy.

PURPOSE: We present a technique that fuses pelvic CT scans and ProstaScint images to localize areas of disease within the prostate gland to customize prostate implants. Additionally, the acute toxicity results from the first 43 patients treated with this technique are reviewed. METHODS AND MATERIALS: Between 2/97 and 8/98, 43 patients with clinical stage II prostate adenocarcinoma received ultrasound-guided transperineal implantation of I-125 or Pd-103 seeds. The median patient age was 70 years (range 49-79). Prior to treatment, the median Gleason score and prostate-specific antigen (PSA) were 6 (range 3-8) and 7.5 (range 1.8-16.6 ng/mL), respectively. The median follow-up was 10 months (range 2.9-20.4 months). RESULTS: The median PSA value at 10 months is 0.7 ng/mL. Significant acute complications within the first month following implantation included 13 Grade I urinary symptoms, 24 Grade II urinary symptoms, 6 Grade III symptoms, and no Grade IV complications. Beyond 4 months, complications included 12 Grade I urinary symptoms, 17 Grade II urinary symptoms, 1 Grade III, and 1 Grade IV complications. CONCLUSIONS: The image fusion of the pelvic CT scan and ProstaScint scans helped identify regions within the prostate at high risk of local failure, which were targeted with additional seeds during implantation.

Neoadjuvant hormonal ablative therapy before radical prostatectomy: a review. Is it indicated?

PURPOSE: Neoadjuvant hormonal ablation therapy has been used to decrease the rate of positive surgical margins in patients treated with radical prostatectomy. We reviewed the available literature to determine whether this therapy is indicated and beneficial. MATERIALS AND METHODS: We performed a MEDLINE key word search and assessed randomized prospective articles. Data were analyzed for the rate of positive surgical margins, seminal vesicle invasion and lymph node metastasis as well as surgical characteristics, including operative time, blood loss, hospital stay, rate of complications and difficulty of surgical dissection. In addition, these data were evaluated for prostate specific antigen-free survival. RESULTS: Neoadjuvant hormonal therapy decreased the rate of positive margins in 6 of the 7 randomized prospective studies. In none of 4 randomized prospective series was there an improved rate of seminal vesicle invasion with neoadjuvant hormonal therapy. Of 4 studies 3 showed no improvement in the rate of lymph node metastasis after neoadjuvant hormonal therapy compared with that in controls. Similarly there was no improvement in prostate specific antigen-free survival and no significant difference in operative time, operative blood loss, transfusion or hospital stay in patients treated with neoadjuvant hormonal therapy and controls. In addition, in 2 of 3 studies there was no difference in the complication rate. CONCLUSIONS: Analysis of the available literature revealed no significant improvement in outcome to support the routine administration of neoadjuvant hormonal therapy before prostatectomy.

Replication linkage study for prostate cancer susceptibility genes.

BACKGROUND: Since the publication of the first genome screen for prostate cancer (CaP) 5 years ago, over a dozen linkage studies have appeared. Most attention has been directed to chromosome 1, where two separate regions have been identified as harboring a prostate cancer susceptibility locus: HPC1 in the 1q24-25 interval and PCaP in the 1q42.2-43 interval. Linkage analysis of chromosome 16 has also provided evidence of harboring two loci predisposing to CaP. METHODS: We report on a replication linkage study of chromosomes 1 and 16 in 45 new and 4 expanded multiplex CaP families. Multipoint Z-scores were obtained for 30 highly polymorphic short-sequence tandem repeat markers spanning chromosome 1, and 22 markers spanning chromosome 16. RESULTS: The replication sample gave no evidence for a CaP susceptibility locus in the 1q24-25 interval and equivocal evidence for such a locus at 1q42.2-43. With respect to chromosome 16, positive Z-scores were obtained over a contiguous interval covering the entire p arm and the proximal half of the q arm. CONCLUSIONS: The linkage analysis of our replication sample does not support the existence of HPC1, and the evidence for the existence of PCaP remains equivocal. Evidence of a susceptibility locus on 16p remains strong, but the evidence for a susceptibility locus on 16q is weakened.