Prostate cancer susceptibility locus on chromosome 1q: a confirmatory study.

BACKGROUND: Recent recognition that a predisposition to prostate cancer can be inherited has led to a search for specific genes associated with the disease. Through a study of families with three or more affected first-degree relatives, a region on the long arm of chromosome 1 (i.e., 1q24-25) has been tentatively identified as containing a gene, HPC1, involved in the development of hereditary prostate cancer. Confirmation of this finding is needed, however, before attempts are made to isolate and characterize the putative HPC1 gene. PURPOSE: To confirm that chromosome 1q24-25 contains a gene relevant to hereditary prostate cancer, we analyzed an independent set of families, each with two or more affected individuals. METHODS: Fifty-nine unrelated families were selected for analysis on the sole criterion that more than one living family member was affected by prostate cancer. DNA samples were subsequently isolated from 130 individuals with the disease. These samples were genotyped at six polymorphic marker sequences (D1S215, D1S2883, D1S466, D1S158, D1S518, and D1S2757) covering the chromosomal region proposed to contain HPC1. The resulting data were analyzed by nonparametric multipoint linkage (NPL) methods, yielding NPL Z scores and corresponding one-sided P values. RESULTS: When the entire set of 59 families was considered, the occurrence of prostate cancer (and, presumably, the HPC1 gene) was most tightly linked to marker D1S466 (NPL Z score = 1.58; P = .0574). Analysis of the 20 families (51 affected individuals) fulfilling one or more of the proposed clinical criteria for hereditary prostate cancer (i.e., three or more affected individuals within one nuclear family; affected individuals in three successive generations [maternal or paternal lineage]; and/or clustering of two or more individuals affected before the age of 55 years) revealed more convincing evidence of disease linkage to chromosome 1q24-25 (maximum NPL Z score [at marker D1S466] = 1.72; P = .0451). The 39 families (79 affected individuals) that did not meet the clinical criteria for hereditary prostate cancer exhibited no significant evidence of disease linkage to DNA sequences at chromosome 1q24-25 (maximum NPL Z score [at marker D1S466] = 0.809; P = .208). The six African-American families in our study contributed disproportionately to the observation of linkage, with a maximum NPL Z score at marker D1S158 of 1.39 (P = .0848) for these families. CONCLUSIONS AND IMPLICATIONS: Our data confirm that chromosome 1q24-25 is likely to contain a prostate cancer susceptibility gene. Future efforts at positional cloning of the HPC1 gene should focus on families who meet the proposed clinical criteria for hereditary prostate cancer.

Radical prostatectomy for clinically localized prostate cancer: long-term results of 1,143 patients from a single institution.

PURPOSE: To determine the efficacy and complication rate of radical prostatectomy (RP) as a treatment option for clinically localized prostate cancer (clinical stage < or = T2c). METHODS: The study was a retrospective analysis of 1,143 consecutive patients (median age, 64 years; range, 38 to 79 y) who underwent RP at one institution (mean follow-up time, 9.7 years). Complications for this study population were compared with those of a contemporary group of 1,000 consecutive patients. RESULTS: Of 1,143 patients, 83 (7%) had a low clinical stage (T1) and 160 (14%) had a low histologic grade (Gleason score < or = 3); 648 (57%) had a high clinical stage (T2b or T2c) and 204 (18%) had a high histologic grade (Gleason score > or = 7). Only 113 (10%) died of prostate cancer, and 177 (15%) developed metastasis. Adjuvant treatment (androgen deprivation or radiation therapy) was given in 197 (17%) patients (> or = pT3) and provided virtually identical results as without adjuvant treatment. The 10- and 15-year crude survival rates for 1,143 patients were 75% +/- 1.5% (SE) and 60% +/- 2.2%, respectively; the cause-specific survival rates were 90% +/- 1.1% and 83% +/- 1.9%, respectively; and the metastasis-free survival rates were 83% +/- 1.3% and 77% +/- 1.9%, respectively (398 men at risk at 10 years and 138 men at risk at 15 years). The 10-year survival rate for patients with Gleason score > or = 7 was 74% +/- 3.9%. Only tumor grade was a significant predictor for disease outcome. The hospital mortality rate decreased from 0.7% for the 1,143 study patients to 0% for the more recent 1,000 patients. Severe incontinence declined to 1.4% for the more recent 1,000 patients. Most patients who underwent RP were healthy (Charlson comorbidity index). CONCLUSION: Survival at 15 years was similar to the expected survival rate. Current morbidity and mortality rates associated with RP were extremely low. Thus, RP has been a viable management option for men with clinically localized prostate cancer who have a life expectancy of more than 10 years.

Prostate-specific antigen as a pretherapy prognostic factor in patients treated with radiation therapy for clinically localized prostate cancer.

PURPOSE: This study was conducted to determine the value of prostate-specific antigen (PSA) as a pretherapy prognostic factor for localized prostate cancer treated with primary irradiation (RT). PATIENTS AND METHODS: Between March 1987 and December 1990, 254 patients with pretherapy PSA determinations were treated for clinical stage A2 to C prostate adenocarcinoma. In conjunction with other prognostic factors, pretherapy PSA was evaluated to determine whether it had independent predictive value for disease outcome. RESULTS: Pretherapy PSA was highly and directly correlated with clinical stage, tumor grade, and acid phosphatase level. With a median follow-up duration of 24 months, 241 patients (95%) were fully assessable for disease outcome. In these patients, PSA and tumor grade were the sole independent predictive factors for tumor relapse (ie, clinically determined and/or increasing PSA level). The combination of pretherapy PSA and tumor grade information defined groups of patients with distinctly different outcome. For patients in low- (favorable PSA and tumor grade), intermediate- (favorable PSA or tumor grade), and high- (adverse PSA and tumor grade) risk categories, the actuarial rates of survival free of tumor relapse or increasing PSA level were 94%, 77%, and 42% at 3 years, respectively (P < .0001). CONCLUSION: Pretherapy PSA is a strongly independent prognostic factor for disease outcome following primary RT. The combination of adverse pretherapy PSA and unfavorable tumor grade identified a cohort of patients with a high risk of early treatment failure in whom combined modality therapy may be appropriately investigated.

New diagnostic and treatment guidelines for benign prostatic hyperplasia. Potential impact in the United States.

BACKGROUND: The Agency for Health Care Policy and Research (AHCPR) recently released the clinical practice guidelines for the diagnosis and treatment of benign prostatic hyperplasia. Prevalence estimates from a population-based cross-sectional study, the baseline component of a cohort study of the natural history of prostatism, were used to assess their potential impact in the United States. METHODS: The study group comprised a population-based sample of white men aged 50 to 79 years who were randomly selected within age- and residence-specific strata from the Olmsted County, Minnesota, population (1990 census, 105,720). These 1317 men completed symptom assessments and diagnostic evaluations that paralleled the AHCPR guidelines, including the measurement of urinary flow rates and, for a subset (n = 303), ultrasonic determination of postvoiding residual urine volume. RESULTS: The application of the AHCPR benign prostatic hyperplasia diagnostic guidelines to the study cohort (American Urologic Association Symptom Index > 7 and peak urinary flow rate < 15 mL/s) suggests that 17% of men aged 50 to 59 years, 27% of men aged 60 to 69 years, and 35% of men aged 70 to 9 years are eligible to discuss treatment options. Application of these percentages to the 1990 US white population suggests that approximately 5.6 million men aged 50 to 79 years are eligible to discuss treatment options. This number will double by the year 2020 owing to the aging of the population. CONCLUSION: The projected number of men potentially meeting AHCPR guidelines to discuss treatment options for benign prostatic hyperplasia could have a substantial impact on the health care system; this will be compounded by the aging of the population.

Predictive properties of serum-prostate-specific antigen testing in a community-based setting.

BACKGROUND: Most studies that have described the sensitivity and specificity of prostate-specific antigen (PSA) as a screening test have been conducted in urology practice settings or in media-based screening programs. The control patients from these settings may have a higher prevalence of urologic disorders that increase serum PSA levels than that of the general population in which screening efforts might take place, leading to biased estimates of sensitivity and specificity. OBJECTIVE: To determine the sensitivity and specificity of serum PSA levels for the early detection of prostate cancer in a population-based setting. PATIENTS AND METHODS: This population-based case-control study was conducted in Olmsted County, Minnesota, where the Rochester Epidemiology Project could identify all incident cases of prostate cancer through passive surveillance of medical care provided to local residents. Case patients were all 177 men (age range, 50-79 years) who were newly diagnosed as having prostate cancer from 1990 through 1992 and had a prediagnostic serum PSA determination (90% of all incident cases). Control patients were randomly selected from the Olmsted County population and had undergone a clinical examination to exclude prostate cancer. RESULTS: The median (25th and 75th percentiles) of serum PSA levels was 9.4 ng/mL (5.4 and 18.6 ng/mL, respectively) for case patients and 1.2 ng/mL (0.7 and 2.1 ng/mL, respectively) for control patients (P < .001). When sensitivity was plotted against 1-specificity, the area under the receiver operating characteristic curve was 0.94 (SE, 0.01). The predictive power declined somewhat with age, with areas under the curve of 0.96, 0.94, and 0.90 for men in their 50s, 60s, and 70s, respectively. When cases were restricted to the 155 men with clinically localized disease, the area under the curve was essentially unchanged (0.94; SE, 0.01) and still much greater than the estimates of 0.75 that were reported from urology practice- and media-based settings. CONCLUSIONS: In a community-based setting, serum PSA levels provide better discrimination between men with and without clinically localized prostate cancer than has been observed in studies that were conducted in urologic practices. These results suggest that previous decision analyses may have underestimated the predictive value of PSA for the detection of prostate cancer in a primary care or community-wide screening program.

The effect of inhibition of aromatase enzyme activity on Leydig cell number and ultrastructure in beagles.

We have shown previously that administration of an orally active competitive aromatase inhibitor 4-(5,6,7,8-tetrahydroimidazo [1,5a] pyridin-5-yl) benzonitrile monohydrochloride to adult male beagles increases peripheral blood LH and testosterone concentrations, and that testes from treated dogs produce more testosterone when perfused in vitro than age-matched controls. In the present study we posed the question of whether the increased testosterone secretion by testes from these same aromatase-treated dogs was due to Leydig cell hypertrophy or hyperplasia, and if the latter, whether cytoplasmic organelles are increased. Beagles were treated with the inhibitor at a dosage of 2.5 mg/kg.day for 25 weeks and were euthanized by an overdose of iv sodium pentobarbital; testes were perfusion-fixed, embedded, and sectioned for stereological analysis. There were no significant differences in testis volume and absolute volumes of seminiferous tubules, blood vessels, lymphatic space, macrophage cells, and mesenchymal cells between the control and treated dogs. In contrast absolute interstitium volume and the absolute volume of Leydig cells per testis were significantly increased (P less than 0.05) in treated dogs. This increased Leydig cell volume per testis was due to increased volume of individual Leydig cells rather than to increases in Leydig cell number per testis. Additional studies showed that the surface area per Leydig cell of smooth endoplasmic reticulum, outer and inner mitochondrial membranes, and membranes of lipid droplets per testis were significantly higher (P less than 0.05) in the treated dogs as compared to the controls. In summary, the results of this study lead us to conclude that aromatase inhibition in the mature dog causes Leydig cell hypertrophy rather than hyperplasia and increased surface area per Leydig cell of subcellular organelles that contain enzymes involved in steroid biosynthesis.

Prostate cancer screening and beliefs about treatment efficacy: a national survey of primary care physicians and urologists.

PURPOSE: To describe practice patterns and beliefs of primary care physicians and urologists regarding early detection and treatment of prostate cancer. SUBJECTS AND METHODS: National probability samples of primary care physicians (n=444) and urologists (n=394) completed mail survey instruments in 1995. Physicians were asked about their use of prostate-specific antigen (PSA) testing for men of different ages and their beliefs about the value of radical prostatectomy, external-beam radiation therapy, and watchful waiting for men with differing life expectancies. RESULTS: Most primary care physicians report doing PSA tests during routine examination of men older than 50 years of age. The majority say they continue to do them on patients over 80 years and to refer men with abnormal values for biopsy. In contrast, only a minority of urologists would recommend PSA tests or biopsy for abnormal values for men over 75 years of age. More than 80% of primary care physicians and urologists doubt the value of radical prostatectomy for men with < 10 years of life expectancy; more primary care physicians than urologists see probable survival benefit in radiation therapy for patients with life expectancy < 10 years (48% versus 36%) or > 10 years (67% versus 53%). Thirteen percent of primary care physicians and only 3% of urologists consider watchful waiting to be as appropriate as aggressive therapy for men with > 10 years of life expectancy. CONCLUSIONS: Primary care physicians are more aggressive about PSA testing and referral for biopsy than most urologists recommend. Both groups recommend PSA testing and believe that aggressive treatment is more beneficial than existing evidence indicates.

Correlation of pretherapy prostate cancer characteristics with histologic findings from pelvic lymphadenectomy specimens.

PURPOSE: The purpose of this study was to identify pretherapy factors associated with pelvic lymph node involvement (LNI) in patients with localized prostatic carcinoma (CaP), and to develop a model that would allow for estimation of this risk at the time of initial diagnosis. METHODS AND MATERIALS: Between January 1988 and December 1992, 2439 patients with clinical Stage T1a-3cN0-XM0 CaP underwent radical retropubic prostatectomy and bilateral pelvic lymph node dissection as sole initial therapy at a single medical institution. Preoperative factors were evaluated for their association with pelvic LNI in univariate and multivariate logistic regression analysis. A model was developed that incorporated independent predictive variables, and probability plots were generated to estimate the likelihood of pelvic LNI in the patient with a new diagnosis of localized CaP. RESULTS: Within clinical tumor stage, three groups (Tla-2a, T2b-c, and T3) were identified in which the observed rate of pelvic LNI was distinctly different. Gleason primary grades were also combined (1-2, 3, and 4-5) because of a similar observation. Univariate analysis identified clinical tumor stage (p < 0.0001), Gleason primary grade (p < 0.0001), and serum prostate-specific antigen (p < 0.0001) as factors associated with pelvic LNI. Each of these variables retained independent significance (p < or = 0.0002) in the multivariate model. Patient age (p = 0.12) and history of prior transurethral resection of the prostate (p = 0.36) were not found to correlate with this endpoint. Probability plots provided an estimate of the likelihood for pelvic LNI according to the combination of pretherapy clinical tumor stage, Gleason primary grade, and serum prostate-specific antigen level. CONCLUSION: Clinical tumor stage as determined by digital rectal examination, Gleason primary grade of the diagnostic biopsy specimen, and pretherapy serum prostate-specific antigen value can be combined to estimate the probability of pelvic LNI for the patient with a new diagnosis of localized CaP. This information may be of value in directing the pretherapy diagnostic evaluation, as an aid in radiation therapy treatment planning, and in the conduct of clinical research efforts.

Effect of several recruitment strategies on response rates at baseline in a prospective cohort investigation. The Olmsted County Study of Urinary Symptoms and Health Status among Men.

Epidemiologic survey response rates were studied in relation to maneuvers introduced to improve acceptance: (a) variation in invitation letters, (b) the use of a brochure with the recruitment mailing, and (c) options for interview location. The baseline population-based survey of a prospective cohort investigation of the natural history of benign prostatic hyperplasia was used. Invitations to participate were mailed to eligible, randomly selected men aged 40 to 79 years from the Olmsted County, Minnesota, population during 1989 to 1991. Of the 3874 men identified, 2119 (55%) participated. Overall, there was no difference in response rate according to invitation characteristics (chi 2(5) = 8.02, P = 0.16). Nevertheless, response rates varied with age (chi 2(7) = 30.9, P < 0.001) and home location (rural versus Rochester city; chi 2(1) = 76.9, P < 0.001). This suggests the innovations used to bolster acceptance did not materially improve response rates. Further, since response rates were highest for men aged 60 to 74 years, men with more symptoms and free time may have joined the cohort more often than others.

Percent free prostate-specific antigen: entering a new era in the detection of prostate cancer.

The introduction of prostate-specific antigen (PSA) testing into clinical medicine in 1986 revolutionized the management of patients with prostate cancer. The major limitation of this tumor marker stems from its inability to provide a clear distinction between benign prostate disease and prostate cancer, especially in patients with upper limit of normal or slightly increased PSA values. Recent research has established that PSA exists in the serum in several molecular forms. Patients with benign prostatic hyperplasia have more of the free form, whereas those with prostate cancer have more of a complexed form (PSA covalently bound to alpha 1-antichymotrypsin). Several investigations have now confirmed that determining percent free PSA (proportion of free PSA to total PSA) enhances the ability of PSA testing to distinguish between prostate cancer and benign prostatic hyperplasia. In addition, percent free PSA seems to have the greatest clinical significance in patients whose total PSA values range from 2.5 or 3.0 ng/mL (lower limit) to 10.0 ng/mL (upper limit). When the total PSA value is in the normal range (2.5 or 3.0 to 4.0 ng/mL), percent free PSA makes PSA a more sensitive test (increases cancer detection). When the total PSA level is minimally increased (4.1 to 10.0 ng/mL), percent free PSA makes PSA a more specific test (eliminates performance of unnecessary prostate biopsies). Although further work remains, it seems that percent free PSA can substantially improve the clinical utility of the PSA test for detecting early, curable prostate cancer.

Transurethral needle ablation of the prostate: a minimally invasive treatment for symptomatic benign prostatic hyperplasia.

Transurethral needle ablation of the prostate, a relatively new minimally invasive treatment modality for patients with bladder outlet obstruction attributable to an enlarged prostate gland, has undergone extensive evaluation by numerous investigators worldwide. The results to date indicate that needle ablation is safe and effective for relieving symptoms in patients with benign prostatic hyperplasia, and the effect has been demonstrated to be durable for at least 2 years. Nevertheless, additional investigations with longer follow-up data are needed to address the important issues of extended durability (5 to 10 years) and biophysiologic mechanism of action. Comparisons between transurethral needle ablation of the prostate and transurethral resection of the prostate (TURP) have revealed that the subjective and objective measures of response are comparable, although TURP has consistently displayed a slight advantage over needle ablation for most variables analyzed, except quality of life score. The advantages of needle ablation over TURP are (1) performance in the office as an outpatient procedure, (2) no need for general or spinal anesthesia, (3) rapid recovery, (4) minimal side effects, and (5) one-time intervention. The following disadvantages exist with needle ablation: (1) it may not be indicated or effective in patients with large prostate glands (75 g or more); (2) no prostate tissue is available for histologic evaluation; and (3) no long-term efficacy or re-treatment rate data have been published. Overall, the available information indicates that transurethral needle ablation is a viable minimally invasive treatment that may be applicable in men with moderate to severe bladder outlet obstruction as a result of an enlarged prostate gland.

Medical treatment of benign prostatic hyperplasia: 5 alpha-reductase inhibitors and alpha-adrenergic antagonists.

Benign prostatic hyperplasia (BPH), a nonmalignant neoplasm of the prostatic epithelial and stromal tissue, occurs commonly in elderly men. The "gold standard" of care for symptomatic BPH has been and remains transurethral resection of the prostate. This operation, however, like any surgical procedure, has associated morbidity and imposes an appreciable expense on the health-care system; therefore, enthusiasm for the development of medical therapies for the management of symptomatic BPH has been substantial. Currently, practicing physicians have two types of medications for the treatment of symptomatic BPH: 5 alpha-reductase inhibitors and alpha-adrenergic antagonists. The former drugs inhibit the conversion of testosterone to the potent prostatic androgen dihydrotestosterone. As a result, the androgenic stimulation to the prostate gland is suppressed, and the size of the prostate is decreased by approximately 25%. In some patients, this outcome decreases the mechanical obstruction of the prostatic urethra and improves micturition. alpha-Adrenergic antagonists decrease the smooth muscle tone of the bladder neck, prostatic adenoma, and prostatic capsule. After these structures have been relaxed, resistance to urine flow through the prostatic urethra can be decreased, and obstructive voiding symptoms can be resolved. Although two distinctly different mechanisms are involved, both types of medications are effective for treating BPH. Thus, in 1993, transurethral resection of the prostate is no longer the only available therapeutic option. With the advent of medical therapies, internists and primary-care physicians will have more involvement in the care of patients with BPH than previously. Therefore, urologists and nonurologists must work together to serve the needs of patients with prostatism.

Prostate-specific antigen, digital rectal examination, and transrectal ultrasonography: their roles in diagnosing early prostate cancer.

In this article, we review the current status of early detection of prostate cancer. From existing data in the medical and urologic literature, we developed an algorithm that uses the three current methods of detection: digital rectal examination (DRE), determination of the prostate-specific antigen (PSA) value, and transrectal ultrasonography (TRUS). Prostatic malignant disease is an increasing medical problem in the United States. The potential for cure is optimized by early detection and treatment of organ-confined disease. Mass screening for prostate cancer in asymptomatic men cannot be advocated until a decrease in the mortality rate is established by randomized, controlled studies; however, these data will be unavailable for at least 15 years. In the meantime, clinicians must prudently use DRE, PSA, and TRUS for early detection. Current data indicate that the PSA level is as effective as or more effective than DRE for the detection of prostate cancer. These two methods do not always detect the same malignant tumor; therefore, the combined use of DRE and PSA testing provides a more complete evaluation of the prostate gland for malignant involvement. TRUS is more costly and does not add appreciable detectability when results of both the DRE and the PSA determination are normal. Thus, TRUS is best reserved for patients who have abnormal results of DRE or increased PSA values.

Prostate-specific antigen: critical issues for the practicing physician.

BACKGROUND: Serum prostate-specific antigen (PSA), when used in combination with existing detection methods, improves the clinician's ability to detect early and potentially curable prostate cancer. FINDINGS: This report describes clinically important issues about use of the serum PSA concentration for detecting early prostate cancer. Other PSA-related factors--PSA density, PSA velocity, and age-specific reference ranges--seem to enhance the ability of clinicians to distinguish benign prostatic conditions from early prostate cancer. Because digital rectal examination only minimally affects the serum PSA concentration, delaying a determination after this examination is unnecessary. Finasteride therapy for benign prostatic hyperplasia should be initiated only after the prostate has been evaluated for cancer because this 5 alpha-reductase inhibitor lowers the serum PSA value by approximately 50%; however, reassessment of the prostate for cancer is necessary if the PSA level fails to decrease as expected or increases to more than 2 ng/mL during finasteride treatment. CONCLUSION: Currently, PSA is the most important, accurate, and clinically useful tumor marker for prostate cancer.

Prostate-specific antigen: concepts for staging prostate cancer and monitoring response to therapy.

FINDINGS: The prostate-specific antigen (PSA) level alone does not facilitate precise pathologic staging on an individual basis, although advanced stage tends to correlate with an increased PSA level. The staging accuracy of PSA, however, can be enhanced by considering the variables of tumor grade and clinical stage. Staging radionuclide bone scans in asymptomatic, untreated patients with clinically localized prostate cancer and a PSA value of less than 10.0 ng/mL are unnecessary. After radical prostatectomy, the serum PSA level is exquisitely sensitive to recurrent or residual disease. Ultrasensitive PSA assays can increase the sensitivity of PSA as a tumor marker after surgical removal of the prostate. Currently, however, the clinical usefulness of PSA concentrations detected in the ultrasensitive range after radical prostatectomy is unknown. Serum PSA values aid in monitoring patients who have received definitive radiation therapy for prostate cancer. Patients in whom the serum PSA level decreases to the reference range have a favorable prognosis. An increasing serum PSA concentration after radiation therapy heralds progressive prostate cancer. The serum PSA level after androgen deprivation therapy (ADT) also has prognostic importance in that a decrease to the normal range predicts a prolonged remission in most patients. Because expression of PSA is under direct hormonal influence, however, ADT can decrease the serum PSA value independent of antitumorigenic activity. Patients who have received ADT must be closely monitored for signs of clinical progression because, in some patients, a serum PSA concentration within the reference range may underestimate actual tumor burden and activity. CONCLUSION: PSA is the most useful and accurate tumor marker for staging and monitoring prostate cancer after therapy.

Sustained, substantially increased concentration of prostate-specific antigen in the absence of prostatic malignant disease: an unusual clinical scenario.

A 60-year-old man had a persistent, marked increase in the serum concentration of prostate-specific antigen (more than 20 times the upper limit of the reference range) and no identifiable prostatic malignant involvement. To our knowledge, this is the first such case reported in the literature. Possible explanations for this increased value are described, and nonmalignant conditions that can increase serum concentrations of prostate-specific antigen are reviewed.

A prospective randomized comparison of epidural infusion of fentanyl and intravenous administration of morphine by patient-controlled analgesia after radical retropubic prostatectomy.

In a prospective, randomized study, continuous infusion of epidural fentanyl citrate (group E) was compared with patient-controlled intravenously administered morphine sulfate (group P) for analgesia in 66 men after radical retropubic prostatectomy. Although both methods provided satisfactory analgesia, the mean comfort level scores were lower (that is, greater comfort) in group E than in group P at all observation times. The difference in mean resting comfort level scores between groups E and P was statistically significant (P < or = 0.05) at 9 of the 11 observation times. In addition, significant differences in comfort level scores were noted at 8 of the 11 observation times during deep breathing, 5 of 11 during coughing, and 3 of 9 during ambulation. Maximal and minimal comfort level scores recorded by each patient during the course of the study were significantly lower (that is, less pain) in group E than in group P for all four categories of activity. The percentage of patients who reported no pain was significantly higher in group E than in group P at 9 of 11 observation times during resting and 5 of 11 observation times during deep breathing. No significant differences were noted in side effect profiles or duration of hospital stay. In summary, when two effective methods of analgesia used after radical retropubic prostatectomy were compared prospectively, patients who received epidural infusion of fentanyl were more comfortable than those with patient-controlled intravenous administration of morphine, as evidenced by lower mean, maximal, and minimal comfort level scores and a greater proportion of patients with complete relief of pain.

Adverse effects of medications on urinary symptoms and flow rate: a community-based study.

The relationship between urinary symptoms and medication use was investigated in a community-based cross-sectional study involving a random sample of 2115 men 40-79 years of age in Olmsted County, Minnesota. The American Urological Association Symptom Index (AUASI) was generated from a validated self-administered questionnaire. Medication use was assessed by in-person interviews. While 1087 men reported daily medication use, only 136 reported daily use of medications known to affect urinary function adversely, including antidepressants (42), antihistamines (23), and bronchodilators (43). Age-adjusted AUASI scores were higher in men reporting daily use of antidepressants, and the association persisted after additionally adjusting for the Depression and Anxiety subscales of the General Psychological Well-Being Scale (adjusted mean difference, 2.1; 95% confidence interval (CI), 0.5-3.6; p = 0.008). The adjusted AUASI was also higher among men who took antihistamines daily (adjusted mean difference, 2.3; 95% CI, 0.3-4.3; p = 0.03). Lower age-adjusted urinary flow rates occurred with antidepressants, but not with antihistamines or bronchodilators. Clinicians evaluating men for causes of voiding dysfunction in accordance with the Agency for Health Care Policy and Research practice guideline for the diagnosis and management of benign prostatic hyperplasia should be aware that daily use of antidepressants or antihistamines may be associated with AUASI scores that are two to three points higher than in men not taking these medications.

Validation of a new quality of life questionnaire for benign prostatic hyperplasia.

In planning a longitudinal study to characterize the natural history of benign prostatic hyperplasia (BPH), we validated a new disease-specific quality of life questionnaire in a pilot study. We studied 110 men in Rochester, Minnesota who spanned the severity of BPH, from men with no known BPH to men who underwent surgery for this condition. Baseline data were obtained on all men, and the 30 who underwent prostatectomy were re-interviewed to test responsiveness. Reproducibility was examined on the pre-post responses (10 weeks apart) of the 37 men with BPH who did not undergo prostatectomy. Six of twelve question domains were retained in the final questionnaire on the basis of their responsiveness to change, reproducibility, internal consistency, and validity. These were: urinary symptoms, degree of bother due to urinary symptoms, BPH-specific interference with activities, general psychological well-being, worries and concerns, and sexual satisfaction. Most of the more generic measures were deleted.

The natural history of prostatism: the effects of non-response bias.

BACKGROUND: In epidemiological studies, non-response may raise the question of generalizability to the target population. Most investigations have not been able to access data that could provide information about the potential impact of non-response bias. METHODS: A 55% response rate was realized at baseline for a prospective cohort investigation of the natural history of benign prostatic hyperplasia in Olmsted County, Minnesota, during 1989-1991 (the Olmsted County Study of Urinary Symptoms and Health Status Among Men). This prompted a preliminary study of potential non-response bias among full participants, partial participants and complete non-responders. The medical diagnostic index maintained by the Rochester Epidemiology Project was used to ascertain the prevalence of specific conditions in the 9 years prior to study inception. RESULTS: The age-adjusted period prevalence rate for benign prostatic hyperplasia (%) was 9.6 (95% confidence interval [CI]: 8.1-11.0) for full participants, 8.2 (95% CI: 5.8-10.6) for partial participants and 5.3 (95% CI: 3.6-6.9) for complete non-responders. Other urologic diagnoses followed the same pattern. However, age-adjusted prevalence rates for general medical examination history and major non-urologic morbidities were decidedly similar across response groups. CONCLUSIONS: These data suggest response may have been driven, in part, by concerns about urologic disease. However, the similarity in non-urologic diagnoses and general medical examinations provide some preliminary reassurance that the 55% response rate did not necessarily compromise generalizability.