Differential alterations in 5alpha-reductase type 1 and type 2 levels during development and progression of prostate cancer.

BACKGROUND: In the prostate, conversion of testosterone to dihydrotestosterone (DHT), by the enzymes 5alpha-reductase types 1 and 2 (5alphaR1, 5alphaR2) is required for normal growth and probably also for development of prostate cancer (PCa). Finasteride, a 5alphaR2 inhibitor, was shown to reduce the prevalence of PCa in the Prostate Cancer Prevention Trial. However, inhibition of both 5alphaR isoenzymes causes a greater decrease in serum DHT. The aim of this study was to assess differential expression of these enzymes at various stages of PCa development. METHODS: Immunostaining for 5alphaR1 and 5alphaR2, using specific, well-validated antibodies, was evaluated in 26 benign prostatic hyperplasia (BPH) (16 for 5alphaR2), 53 primary PCa (21 for 5alphaR2), 18 prostatic intraepithelial neoplasia (PIN), 12 primary PCa treated with neoadjuvant androgen ablation, 15 locally recurrent PCa specimens, and 18 PCa metastases. RESULTS: The mean area of moderate plus high intensity staining for 5alphaR1 increased from 4.8 +/- 2.8% of total epithelial area in BPH, to 18.9 +/- 5.7% in PIN, 17.0 +/- 3.2% in primary cancer, 38.0 +/- 7.3% in recurrent cancer, and 55.8 +/- 8.5% in PCa metastases. The mean staining area for 5alphaR2 decreased from 58.8 +/- 7.2% in BPH, to 21.1 +/- 5.5% in PIN and 34.8 +/- 6.7% in primary PCa. Staining for 5alphaR2 was increased in recurrent cancer and PCa metastases compared to primary PCa, at 58.7 +/- 5.2% and 69.2 +/- 8.7%, respectively. CONCLUSIONS: 5alphaR1 immunostaining is increased and 5alphaR2 immunostaining is decreased during development of PCa. In addition, there is increased expression of both 5alphaR isozymes in recurrent and metastatic cancers, suggesting that both isozymes may be important in the development and progression of PCa.

Assessing self-help issues for patients with prostate cancer, interstitial cystitis, erectile dysfunction and urinary diversion.

OBJECTIVE: To determine the prevalence of self-help (which is widely available and can assist clinicians to educate and empower patients) for several urological diseases. PATIENTS AND METHODS: Using a structured interview, the prevalence of self-help use and awareness was assessed in patients with prostate cancer, interstitial cystitis, erectile dysfunction and urinary diversion. Patients were also asked to report levels of support and information they required and to specify how well these needs were being met. Consecutive patients (120, 30 from each group) were recruited from an outpatient urology clinic in a tertiary-care health centre. RESULTS: Patients with interstitial cystitis and erectile dysfunction reported having the greatest need but were least satisfied with the level of support and information they currently receive. Inversely, patients with prostate cancer reported having the least need and were most satisfied. Excluding brochures, the use and awareness of self-help were low in all groups but most patients claimed they would use many types of self-help if they were available. Many patients are not directed to self-help resources by their urologist or family physician. CONCLUSION: Most patients would like to use more self-help but many do not. The low percentage of patients referred to self-help by their physician probably contributes to, or causes, this problem. It is important for clinicians to encourage and refer patients to specific resources to ensure that the patient receives accurate and pertinent information. As most patients read brochures it is logical to use them to provide basic information and to direct them to other more sophisticated forms of self-help. We have used urology patients as a model but consider that many of our findings could be applied to other medical and surgical specialties.

5alpha-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium.

PURPOSE: In the prostate testosterone is converted to the more potent androgen dihydrotestosterone by the enzymes 5alpha-reductase (5alphaR) types 1 (5alphaR1) and 2 (5alphaR2). Since 5alphaR2 is the dominant prostatic enzyme, the 5alphaR2 selective inhibitor finasteride has been widely used to treat benign prostatic hyperplasia (BPH). However, inhibition of both 5alphaR enzymes provides a greater decrease in serum dihydrotestosterone. We developed a specific antibody to 5alphaR1 and assessed expression in BPH and prostate cancer (pCa) tissue. The presence of this isoenzyme in localized prostate cancer would provide a rationale for assessing the efficacy of dual inhibition for prostate cancer prevention. MATERIALS AND METHODS: A polyclonal antibody to 5alphaR1 was developed and validated using 5alphaR1 and 5alphaR2 transfected COS-1 cells. A total of 26 BPH and 53 pCa specimens were assessed for 5alphaR1 protein expression using immunocytochemical methods. Also, 29 BPH and 37 pCa specimens were assayed for 5alphaR1 and 5alphaR2 enzyme activity. RESULTS: Specificity of the 5alphaR1 antibody was confirmed using transfected COS-1 cells. Cells transfected with 5alphaR1 showed specific staining in immunocytochemistry experiments and on Western blotting of cell lysates the expected 24 kDa band was observed. High intensity immunoreactivity for 5alphaR1 was observed in the tumor epithelium of 28% of pCa specimens. No high intensity epithelial staining was observed in BPH specimens. In 19% of pCa and 7% of BPH specimens 5alphaR1 enzyme activity was detected. CONCLUSIONS: The presence of increased 5alphaR1 in some prostatic malignancies suggests that it is worthwhile to investigate the use of a dual 5alphaR inhibitor to prevent or treat early stage prostate cancer.

The role of self-help groups in educating and supporting patients with prostate cancer and interstitial cystitis.

OBJECTIVES: To identify and compare the needs of patients with prostate cancer or interstitial cystitis (IC), and to evaluate the role of self-help groups (SHGs) in meeting those needs, as SHGs are thought to be an important source of information and social support for such patients. METHODS: The authors attended SHG meetings for prostate cancer and IC from September 2000 to May 2001. Issues related to SHGs were addressed by combining their experiences with those published previously. RESULTS: Patients with prostate cancer appear to use SHGs primarily as a medium for advocacy and information sharing about the disease, whereas patients with IC seem to use SHGs for social support and coping skills. Patients perceive SHGs as being useful, but many do not attend these meetings. Urologists' attitudes toward SHGs are identified as a potential factor contributing to the under-use of SHGs by both groups of patients. CONCLUSIONS: The inherent differences in disease and patient characteristics result in both groups of patients using SHGs for different reasons. The differences in therapeutic objectives are reflected in the format and content of SHG meetings. Issues related to not participating in SHGs and areas of future research are discussed.

Optimal prevention and management of proximal ureteral stent migration and remigration.

PURPOSE: We evaluated issues associated with proximal ureteral stent migration and remigration, including causes and management, and the predictability of ureteral length. MATERIALS AND METHODS: All proximal ureteral stent migrations that occurred from January 1997 to March 2000 were reviewed. Characteristics and treatment of the 33 patients with proximal ureteral stent migration were compared with those of 66 randomly selected controls who did not have stent migration. We also analyzed a subgroup of 6 cases of remigration. RESULTS: Of the ureteral stents 2% migrated proximally. Mean height was greater in patients with versus without a migrated stent (p = 0.028). The stent-to-ureter length ratio was lower in the migrated than in the nonmigrated group (p <0.0001). Patient height and side of migration were significant predictors of ureteral length (R2 = 0.3511, p <0.0001 and 0.0007, respectively). Of the patients who required continued ureteral stenting migrated stent management included placement of a longer stent in 9 (group 1) and a stent of equal length in 4 (group 2), and repositioning of the original stent in 4 (group 3). There was no remigration in group 1. However, migration recurred in 2 patients in group 2 (50%) and in all 4 in group 3 (100%). CONCLUSIONS: Proximal migration occurs when a stent is too short for the ureter. We recommend that ureteral length should be measured directly from an x-ray to select the optimal stent length. If it is necessary to continue stenting a ureter after migration has been detected, a longer stent should be placed.

Biomechanical and psychosocial risk factors for low back pain at work.

OBJECTIVES: This study determined whether the physical and psychosocial demands of work are associated with low back pain. METHODS: A case-control approach was used. Case subjects (n = 137) reported a new episode of low back pain to their employer, a large automobile manufacturing complex. Control subjects were randomly selected from the study base as cases accrued (n = 179) or were matched to cases by exact job (n = 65). Individual, clinical, and psychosocial variables were assessed by interview. Physical demands were assessed with direct workplace measurements of subjects at their usual jobs. The analysis used multiple logistic regression adjusted for individual characteristics. RESULTS: Self-reported risk factors included a physically demanding job, a poor workplace social environment, inconsistency between job and education level, better job satisfaction, and better coworker support. Low job control showed a borderline association. Physical-measure risk factors included peak lumbar shear force, peak load handled, and cumulative lumbar disc compression. Low body mass index and prior low back pain compensation claims were the only significant individual characteristics. CONCLUSIONS: This study identified specific physical and psychosocial demands of work as independent risk factors for low back pain.

Metabolic evaluation of stone disease patients: a practical approach.

The high success rates of extracorporeal shockwave lithotripsy and endourological techniques, together with their ease of use, in the treatment of urinary stones often overshadow the importance of the metabolic component of stone disease. It is my opinion that the prevention of further stones complements management of the acute episode. This review summarizes a variety of approaches to the measurement and manipulation of individual risk factors in recurrent urinary stone disease.

Primary extranodal lymphoma of the scrotum.

Primary extranodal lymphomatous involvement of the skin or genitourinary tract is rare. We report a case of primary scrotal diffuse large cell non-Hodgkin's lymphoma in a 78 year-old male.

Prostate cancer in a hypogonadal male receiving androgen supplementation.

Although androgen supplementation is clearly indicated in most hypogonadal males, it is also gaining popularity in the health management of the aging male without clearly low testosterone levels as the concept of male menopause becomes more accepted and recognized. The benefits include improved energy, sexual function and bone strength. A potential downside of exogenous androgen is the provocation of an underlying prostate cancer, which now represents the most common type of cancer and the second most common cause of cancer death among men in Canada. This problem is illustrated in our case of prostate cancer in a hypogonadal male on androgen supplementation. We recommend that serum PSA and digital rectal examination (DRE) be performed prior to the initiation of and regularly throughout the course of androgen supplementation. Changes in either should be investigated appropriately and termination of androgen supplementation should be considered an important component of management of prostate cancer in these patients.

Effects of dietary fat on the urinary risk factors of calcium stone disease.

OBJECTIVES: To assess the association between dietary fat and various urinary risk factors of calcium stone disease in a group of calcium stoneformers attending an outpatient stone clinic. METHODS: Mean daily fat intake from self-recorded 4-day dietary food records and mean 24-hour urinary risk factors from two separate collections were evaluated in 476 patients selected randomly from an adult population attending an outpatient stone clinic for the first time. RESULTS: Mean daily total fat intake for men and women was significantly different at 105.6 and 78.1 g, respectively. Examination of the relationship between total fat intake and 24-hour urinary volume, pH, and excretions of magnesium, citrate, oxalate, calcium, and uric acid revealed no significant regressions in men and only a weak association between fat intake and urinary uric acid in women. CONCLUSIONS: Dietary fat does not have a significant effect on the urinary risk factors of calcium stone disease.

The dietary habits of idiopathic calcium stone-formers and normal control subjects.

OBJECTIVES: To examine the relationship between 12 macro- and micro-nutrients and the risk of recurrent calcium stone formation by comparing the diets of a large outpatient clinic-based group of patients who had formed calcium-based urinary tract calculi with that of a population-based control group matched for age, gender and body mass index. PATIENTS, SUBJECTS AND METHODS: The dietary intake of 500 patients (cases) randomly selected from the adult population attending an outpatient renal-stone clinic and being evaluated and/or treated for biochemically or radiologically diagnosed calcium-based upper urinary tract calculi were compared with those of 500 control subjects selected to match for age, sex and body mass index from a stratified probability sample of 2212 adults (not institutionalized) living in the same geographical area. RESULTS: Comparing the mean nutritional intakes showed a statistically higher consumption of energy, carbohydrates, sodium, fibre, vitamin C, fat and folic acid among cases than in controls. The intake of calcium, alcohol and vitamin A was significantly higher among the controls. There were no significant differences in the intake of protein, niacin or iron. The results of these comparisons varied when the groups were stratified by sex, age and body mass index. CONCLUSIONS: Dietary risk factors for calcium-based urinary tract calculi are many and complex, and a detailed consideration of sex, age and body mass index is important in interpreting such data. While it is difficult to draw firm conclusions about causes and effects of individual nutrients from the available data, this study indicates a possibly more important role for dietary fat in stone formation than has been previously recognized. This relationship needs to be further explored in relation to urinary risk factors, as it may be possible to advise patients to reduce dietary fat as a prophylactic measure for stone formation. As dietary fat has been associated with cardiovascular diseases and possibly cancer, an overall recommendation to these patients for a low dietary fat intake may be easier to follow.

Serum phosphate in stone formers: what does a low serum phosphate level mean?

PURPOSE: Metabolic evaluation is indicated in stone formers to identify and subsequently modify risk factors for nephrolithiasis. Some believe that serum phosphate may be an important indicator of nephrolithiasis risk. We determined whether serum phosphate is an independent risk factor for recurrent calcium stone formation and whether it may be used as an early marker for occult disease, such as hyperparathyroidism. MATERIALS AND METHODS: The charts of all patients with regular long-term stone clinic followup were reviewed. Initial serum phosphate levels were compared with stone recurrence, complications due to stones, initial visit urinary laboratory values and the medical diagnoses made during followup. Unpaired 2-sample t tests, and correlation and logistic regression analyses were performed with statistical significance at p <0.05. RESULTS: Data were available on 51 men and 25 women 22 to 74 years old (mean age 52). Of the patients 50 were recurrent and 26 were single stone formers. Serum phosphate levels were lower in women than in men. No consistent associations existed between initial or future serum phosphate levels and stone recurrence, complications from stones, urinary values or other medical diagnoses made during followup. CONCLUSIONS: Serum phosphate does not appear to be an independent risk factor for urinary tract stone recurrence or complications, or a reliable early predictor of occult disease.

Comparison of four peak spinal loading exposure measurement methods and their association with low-back pain.

OBJECTIVES: This paper examines the performance of 4 different methods of estimating peak spinal loading and their relationship with the reporting of low-back pain. METHODS: The data used for this comparison was a subset of subjects from a case-referent study of low-back-pain reporting in the automotive industry, in which 130 random referents and 105 cases (or job-matched proxies) were studied. The peak load on the lumbar spine was determined using a biomechanical model with model inputs coming from a detailed self-report questionnaire, a task-based check list, a video digitization method, and a posture and load sampling technique. RESULTS: The methods were directly comparable through a common metric of newtons or newton meters of spinal loading in compression, shear, or moment modes. All the methods showed significant and substantial associations with low-back pain in all modes (odds ratios 1.6-2.3). The intraclass correlation coefficients (ICC) showed strong similarities between the checklist and video digitized techniques (ICC 0.84-0.91), moderate similarities between these techniques and the work sampling method (ICC 0.49-0.52), and poor correlations (ICC 0.16-0.40) between the self-report questionnaire and the observer recorded measures. CONCLUSIONS: While all the methods detected significant odds ratios, they cannot all be used interchangeably for risk assessment at the individual level. Peak spinal compression, moment, and shear are important risk factors for low-back pain reporting, no matter which measurement method is used. Questionnaires can be used for large-scale studies. At the individual level a task-based checklist provides biomechanical model inputs at lower cost and equal performance compared with the criterion video digitization system.

Assessment of an EMG-based method for continuous estimates of low back compression during asymmetrical occupational tasks.

Variables, such as peak and accumulated moments and spine compression forces, have been shown to be risk factors for occupational low back pain. Estimates of these forces during prolonged, dynamic, asymmetric tasks using biomechanical models is complex and time-consuming. A simple technique for continuous measurement of these variables over a prolonged period is needed to measure the distribution of spinal loading during both sagittal plane lifts and complex asymmetrical jobs. The aim of this study was to determine whether a linear normalization of erector spinae EMG to spine compression force, called compression normalized EMG (CNEMG), could be used to estimate spinal loading for simulations of asymmetrical occupational tasks. The estimates of spine compression force obtained using the normalized EMG are presented in the form of an amplitude probability distribution function and are compared with estimates of a three-dimensional biomechanical model. The per cent time a worker spends above particular levels of spinal loading of interest, such as the NIOSH action limit for compression, are displayed. Five males performed simulated occupational tasks. The exposure time at a specific level of spine compression force for a combination of three tasks, estimated by CNEMG, was, on average, within 6.5% of the time calculated by the biomechanical model. However, if the task combination was dominated by an axial twisting moment, then the difference was, on average, 13.4%. The difference in magnitude of spine compression at a specific probability was, on average, 14.9% and when axial trunk twist dominated, 30.7%. It is concluded that CNEMG can estimate probability at a specific level of spine compression force when the task combination is characterized by a predominant extensor moment in the sagittal plane. Estimates of spine compression at a specific probability, and estimates obtained during task combinations dominated by an axial twisting moment, are poor.

Impact of a shared decision-making program on patients with benign prostatic hyperplasia.

OBJECTIVES: To determine patient views about the Shared Decision-Making Program (SDP), an interactive videodisk program designed to inform patients with benign prostatic hyperplasia (BPH) about their condition and treatment options and to determine its impact on perceived knowledge and treatment preference. METHODS: Six hundred seventy-eight patients with symptomatic BPH from eight Canadian centers viewed the SDP. Before and after viewing the video, patients answered questionnaires designed to assess treatment preference, knowledge gained, and satisfaction with this educational format. A 1-year follow-up survey was also conducted. RESULTS: Most patients showed a high desire for information and high satisfaction with the SDP; this satisfaction persisted at 1 year. Patients' self-reported knowledge increased significantly (P <0.0001). However, the SDP did not alter initial treatment preferences among those with already formed preferences, although it aided almost half of those initially undecided in forming a preference. Viewing the SDP also appeared to enhance the physician-patient relationship. CONCLUSIONS: Patients saw the SDP as an effective method for teaching patients about BPH and the risks and benefits of various treatments, clarifying particular areas about which many patients appear to have a desire for more information than is often provided. Patients were enthusiastic about the educational value of the program, and their active participation in the decision-making process may actually enhance the physician-patient relationship. Contrary to other studies, we found no significant alterations in treatment preferences. Problems relating to the cost and timely updating of the software need to be addressed for these kinds of programs to realize their full potential.

Penile entrapment injury: a case report.

Penile incarceration is a rarely seen injury that requires urgent medical attention and may provide a challenge to even the most experienced emergency and urologic personnel. Described is a novel method of liberating the penis from a nonexpandable metal ring through a combination of multiple puncture wounds and manual compression after failure of other well-described techniques. Included is a treatment algorithm to guide progression of management options in difficult cases.

"Mirror pain" as an unusual presentation of renal colic.

Although most patients suffering from pain related to upper urinary tract stones feel the discomfort on the same side as the stone, rarely it is perceived on the opposite side. We sought to identify the prevalence of this clinical scenario and to review possible explanations. The charts and x-rays of all patients with unilateral, symptomatic, radiologically identifiable upper urinary tract stones, seen at an outpatient clinic between June 1993 and August 1996, were reviewed retrospectively in terms of the side of the discomfort in comparison to the side of the stone. Three of 631 patients presented with contralateral or "mirror pain" secondary to a renal or ureteric calculus. In each case the symptoms resolved completely following successful extracorporeal shock wave lithotripsy or spontaneous passage of the stone.

Renal cell carcinoma metastatic to the contralateral ureter.

The ureter is an uncommon location for cancer metastases, the majority of which are due to nonurologic cancers such as stomach and breast.(1) Renal cell carcinoma (RCC) metastatic to the ureter has been reported infrequently. We report a case of metachronous metastatic RCC to the contralateral ureter.