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M K Brawer

Publications and source records attributed to M K Brawer.

At least 73 records · Page 4Linked to original sources
PubMed1996

Vasectomy and prostate cancer: a case-control study in a health maintenance organization.

A case-control study was conducted within Group Health Cooperative of Puget Sound to evaluate the relation between prior vasectomy and the risk of prostate cancer. Cases consisted of 175 men newly diagnosed with histologically confirmed prostate cancer during 1989-1991. A total of 258 controls, matched to cases on birth year and membership status, were randomly selected from the general membership of the plan. Information was collected from mailed questionnaires and medical records on medical history, including prior vasectomy, anthropometric measures, family history of prostate cancer, personal habits, and medical care utilization, and demographic factors. Conditional logistic regression analyses showed that the odds ratio for prostate cancer associated with vasectomy was 0.86 (95% confidence interval 0.57-1.32) after adjustment for confounders. The odds ratio estimate did not differ substantially by age at vasectomy or time since vasectomy. However, the odds ratio estimate for prostate cancer associated with vasectomy tended to be increased among men who had a father or brother with prostate cancer. Nevertheless, the increased risk may be related to detection bias or differential participation rates due to both vasectomy status and a family history of prostate cancer. These results suggest no overall association between vasectomy and prostate cancer.

Adult↗
PubMed1996

The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group.

BACKGROUND: Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations. However, the effects of the two types of drugs have not been compared. METHODS: We compared the safety and efficacy of placebo, terazosin (10 mg daily), finasteride (5 mg daily), and the combination of both drugs in 1229 men with benign prostatic hyperplasia. American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year. RESULTS: The mean changes from base line in the symptom scores in the placebo, finasteride, terazosin, and combination-therapy groups at one year were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). The mean changes at one year in the peak urinary-flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). Finasteride had no more effect on either measure than placebo. In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups. CONCLUSIONS: In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone.

Adrenergic alpha-Antagonists↗
PubMed1996

Quantitative microvessel density. A staging and prognostic marker for human prostatic carcinoma.

BACKGROUND: Accurate methods of predicting pathologic stage and malignant potential of carcinoma of the prostate are lacking. Such advances would represent major additions to our ability to recommend therapy and offer prognostic information. Quantitation of microvessel density (MVD) has been shown in a number of organ systems to predict tumor aggressiveness. METHODS: We and others have investigated this modality in preoperative assessment of pathologic stage and freedom from progression in patients with prostatic carcinoma. RESULTS: Unique and useful staging information has been provided and indeed quantitation of MVD has been shown to be a better predictor of the findings of radical prostatectomy than clinical stage, serum prostate specific antigen (PSA), and/or the Gleason score. Applying a variety of therapeutic modalities, quantitative MVD can be shown to provide additional information to predict who will or will not progress. Recent observations have demonstrated that quantitative MVD may be performed on a limited tissue sample provided by prostate core needle biopsy. CONCLUSIONS: Quantitative MVD may provide important staging and prognostic information for males with carcinoma of the prostate. The results may influence the recommendation for additional staging studies, provide stratification of patients for neoadjuvant or adjuvant therapy, assist in technical aspects of definitive therapy, and aid in defining optimum monitoring regimens.

Biopsy, Needle↗
PubMed1996

Age-specific prostate-specific antigen: a reassessment.

BACKGROUND: Our objective was to compare expected survival benefits when screening for prostate cancer with PSA, using an age-specific bound relative to a cutoff of 4.0 ng/ml. METHODS: We used a decision analysis modeling the cancer yield in a cohort screened by both screening tests, and the survival of cancer cases given screen detection and in the absence of screening. Expected cancer yields and positive predictive values were from an ultrasound-guided biopsy series. Stage distributions of screen-detected cases were obtained from the literature. For localized causes, survival given screen detection was assumed to be equal to normal life expectancy for the population. For these cases, survival in the absence of screening was modeled as time from clinical diagnosis to death added to time remaining after time of screen and before clinical diagnosis was made (lead time). For nonlocalized cases at screen detection, survival given screen detection was assumed to be equal to survival in the absence of screening. The average difference between expected survival with and without screening as calculated for age-specific PSA and for PSA > 4.0 ng/ml and compared. RESULTS: Average years of life saved per subject screened using PSA > 4.0 ng/ml were comparable to those using the age-specific bound. Average years of life saved per cancer case, however, appeared to be potentially greater for PSA > 4.0 ng/ml than for age-specific. PSA. PSA > 4.0 ng/ml detected markedly more prostate cancer cases than age-specific PSA. CONCLUSIONS: Using a bound of 4.0 ng/ml for all ages appears to be more efficient in identifying men with cancer in a screening cohort, which translates into a greater expected survival benefit per cancer case.

Aged↗
PubMed1996

Role of transrectal ultrasound and prostate biopsy.

Transrectal ultrasound (TRUS) has revolutionized our ability to image the human prostate. In the present review, we have attempted to present salient observations with respect to this modality. We emphasize its use in combination with biopsy in men who are considered at risk for harboring carcinoma. The relevant English literature is reviewed. In addition, our experience with 2,231 consecutive ultrasound-guided biopsies performed at the University of Washington and the Seattle VA Medical Center is analyzed. TRUS appears to have its primary use in directing the biopsy needle into suspicious areas and in performing the so-called systematic sector approach to biopsy. The role of transrectal ultrasound in staging established malignancy or in monitoring men following therapy remains to be defined. In our experience, carcinoma was detected in 27.2% of the subjects. Carcinoma was found in 30.7% of patients with a hypoechoic sector. Of note, 18.4% of men had their only carcinoma found in isoechoic areas. Failure to biopsy isoechoic sectors would have resulted in missing almost 20% of men with carcinoma. The role of TRUS in men with initially negative biopsy is also discussed. In summary, ultrasound guided biopsy is a useful addition to our armamentarium, particularly with respect to performing biopsy. Future advances in this modality include image enhancement utilizing computer technology as well as the potential additive role of color flow ultrasound.

Adult↗
PubMed1996

Multicenter comparison of the diagnostic performance of free prostate-specific antigen.

OBJECTIVES: This study examined the multicenter clinical performance of noncomplexed (free) prostate-specific antigen (PSA) in men presenting with total PSA values between 2.5 to 20 ng/mL. METHODS: Prebiopsy serum samples were obtained from 1,081 consecutively accrued, histologically diagnosed men between the ages of 40 and 75 years with total PSA values falling between 2.5 and 20 ng/mL. Total PSA was determined by either the Tosoh AIA-1200 or Hybritech method. Free PSA values were determined using the Dianon PSA II immunoradiometric method. Free PSA was expressed as a percentage of total PSA. Immunochemistry was performed at each accrual site. RESULTS: Among men diagnosed with prostate cancer (CaP), only 4% (21/520) had proportions of free to total PSA values > 25%. Conversely, among men with benign prostatic disease, only 2% (13/561) had proportions of free to total PSA values < 7%. These results confirm those of previous research. Differences among sites were found in age and prostate volume. CONCLUSIONS: These data confirm that free PSA values < 7% are highly suspicious for CaP whereas free PSA values > 25% suggest absence of malignancy. The data also suggest that age and/or prostate volume influences the serum level of free PSA but does not affect the diagnostic cutoff points of 7% and 25%. Future analysis is needed to confirm that younger men with small prostates are at higher risk for CaP.

Adult↗
PubMed1996

Screening and early detection of prostate cancer will decrease morbidity and mortality from prostate cancer: the argument for.

Since prostate cancer represents the most common male malignancy and the second most frequent cause of cancer-related mortality, there is a significant need for methods to either reduce the incidence, improve therapy, or provide early detection. Of these, only the latter appears to be currently at hand. Many investigators have demonstrated that early detection programmes, incorporating a carefully performed digital rectal examination and prostate-specific antigen level testing, have resulted in a significant detection rate of clinically relevant malignancy at a time when it is curable. Although problems such as overdetection, lead- and length-time bias, and significant financial burden are associated with prostate cancer screening, if we are to significantly impact the mortality from this disease, such approaches are probably warranted.

Aged↗
PubMed1996

Chemoprevention for prostatic intraepithelial neoplasia.

OBJECTIVES: To evaluate the potential application of chemoprevention strategies in prostatic intraepithelial neoplasia. METHODS: Review of relevant literature on chemoprevention with emphasis on prostate cancer and premalignant lesions. RESULTS: Chemoprevention represents a strategy designed to inhibit or reverse the process of carcinogenesis by administering one or several noncytotoxic chemical compounds. The epidemiology of prostate carcinoma indicates that this cancer is a prime candidate for a strategy aimed at prevention due to the extremely high prevalence rate, rising annual incidence, and long latent interval between the cancer-initiating events and the development of invasive disease. Chemopreventive agents may exert their inhibitory effects at different stages of the multistep carcinogenic process broadly categorized as initiation, promotion, and progression. The synthetic retinoids, polyamine synthesis inhibitors, and antiandrogens are among the compounds shown to have in vitro or in vivo chemopreventive effects in prostate carcinogenesis. A major limitation in the evaluation of such agents in a human prostate cancer is the long duration of clinical trials required to assess the efficacy with an endpoint of cancer development. Premalignant epithelial changes such as prostate intraepithelial neoplasia, or PIN, are highly associated with prostate cancer, and share many molecular features of invasive cancer. If the reversal or inhibition of intraepithelial neoplasia translates to a concomitant reduction in clinically relevant prostate cancer, then the pharmacological modulation of PIN may provide a rapid means to evaluate the effects and benefits of potential chemopreventive agents. CONCLUSION: Men with PIN may represent ideal candidates for chemoprevention protocols. The ideal agent and duration of therapy remains to be defined.

Androgen Antagonists↗
PubMed1996

Prostatic intraepithelial neoplasia: significance and management.

Prostatic intraepthelial neoplasia (PIN) is a putative premalignant change that bears a morphological similarity to prostatic cancer and shows increased frequency, severity, and extent in patients with prostate cancer. This article discusses the evidence for PIN as a premalignant lesion, reviews the morphology, terminology, appropriate grading system, and diagnostic significance of PIN, as well as describes management recommendations for further evaluation when PIN is diagnosed in prostate resection and biopsy specimens. Clinical management of high-grade PIN found in transurethral resection of the prostate (TURP) or prostate biopsy specimens should include repeat transrectal ultrasound (TRUS) and prostate biopsy for early detection of prevalent coexistent prostate cancer. In cases of high-grade PIN, increased surveillance methods have the potential to decrease morbidity and mortality by early cancer diagnosis.

Humans↗
PubMed1995

Serum basic fibroblast growth factor in men with and without prostate carcinoma.

BACKGROUND: Angiogenesis is essential for the growth of neoplasms. Increased vascularity has been associated with human prostatic carcinoma stage and has been shown to offer prognostic information. Basic fibroblast growth factor (bFGF) is a potent angiogenic inducer expressed in malignant prostate tissue. In this investigation, serum bFGF levels were measured in men with and without prostate cancer. METHODS: Serum bFGF was measured using a commercial enzyme-linked immunosorbent assay in archival serum from men with various clinical stages of prostate carcinoma. Sera from men with negative systematic sector biopsies and serum prostate specific antigen (PSA) less than 2.0 ng/ml served as controls. Prostate volume was measured with transrectal ultrasound. RESULTS: Serum bFGF level was significantly higher in men with prostate carcinoma compared with those without (P < 0.0007). Among 44 men (11 with carcinoma) with a serum PSA less than 4.0 ng/ml, only bFGF level was associated with carcinoma (P = 0.008). Using a cutoff of 1.0 pg/ml, bFGF afforded a sensitivity of 83% and specificity of 44% in this group. There was no association between bFGF levels and clinical stage, Gleason score, or prostate volume. CONCLUSIONS: These data demonstrate that serum levels of bFGF are elevated in most men with prostatic carcinoma. Although association with stage was not observed, the finding of significant elevation in most men with carcinoma who have "normal" serum PSA levels may indicate diagnostic utility for this analyte.

Aged↗
PubMed1995

Topography of neovascularity in human prostate carcinoma.

BACKGROUND: All neoplasms require angiogenesis and resulting neovascularity for growth. The authors and others have confirmed the staging and prognostic significance of quantitative microvascularity density (MVD) in human prostate carcinoma (CAP). In the present investigation, the authors sought to identify the specific site of neovascularity within the neoplasm and adjacent benign tissue. METHODS: Histologically benign and malignant tissues from 14 random radical prostatectomy specimens were studied. The tumor edge was defined precisely by immunohistochemistry, suggesting a high molecular weight cytokeratin that stains only the basal cells of benign histology. Microvascularity density quantification was performed using von Willebrand factor antigen immunohistochemistry as previously defined. Five parallel arcs were defined along which vessel density was calculated including arcs within, on the edge, and removed from the neoplasm. RESULTS: In 13 of 14 cases, the highest vessel density was found within the tumor. Significant differences were observed between the edge of the tumor and 2.5 mm within the benign periphery, between the benign and malignant tissue at the border, and between CAP at the edge and CAP 2.0 mm within the neoplasm. These findings suggest a stepwise increase in MVD toward the center of the neoplasm. CONCLUSIONS: These data confirm the authors' previous observation that prostate cancer has approximately a two-fold increase in MVD compared with the benign tissue. Moreover, high vascularization of the center explains the rare finding of necrosis in CAP. These data suggest that angiogenic promoters may have their highest activity in the center of the neoplasm.

Carcinoma↗
PubMed1995

Microvascularity in benign prostatic hyperplasia.

The vascular density of benign prostatic hyperplasia (BPH) has not been characterized. Previously we reported vessel density (vv/mm2) in prostatic carcinoma was twice that of normal prostate [Bigler et al.: Hum Pathol 24:220-226 1993]. To further characterize vessel density in benign prostate tissue we examined 15 cases of BPH obtained by open prostatectomy. Vessels were stained with antibodies to Factor VIII-related antigen, and vessel density was measured using computer-assisted image analysis. Vessel density was analyzed between various histologic tissue types. Mean vessel density in all transition zone tissue was 70.2 vv/mm2. Vessel density in epithelial hyperplastic nodules (mean 99.3, SD 40.7) exhibited density levels similar to those found in prostatic carcinoma (mean 101.4, SD 35.6). Vessel density in epithelial nodules was significantly higher than in non-nodular epithelial tissue (mean 76.7, SD 23.1; P < 0.001, ratio = 1.3). Higher vessel densities were found in hypercellular stromal nodules (mean 64.7, SD 19.1) than in adjacent stromal areas (mean 36.5, SD 15.3; P < 0.001, ratio = 1.8). Overall, vessel density in BPH was higher than previously found in benign tissue measured in radical prostatectomy specimens, especially in areas of nodular morphology.

Capillaries↗
PubMed1995

Assay variability in serum prostate-specific antigen determination.

Consistency and reproducibility of serum prostate-specific antigen (PSA) measurement are essential in the application of this analyte to early detection or screening programs. In the present investigation, we sought to compare serum PSA levels determined by the IMx assay (Abbott Laboratories, North Chicago, IL) and the Tandem E (Hybritech Inc., San Diego, CA) to determine whether there were differences. Two hundred twenty-eight random sera from our archival bank were investigated. One hundred-eight specimens were in the Tandem range of 2.0-10.0 ng/ml, and prostatic histology was known based on either systematic sector needle biopsy or transurethral resection. PSA was measured with three different lost of the IMx and Tandem assays. Over the entire range, there was a good correlation (r2 = 0.985); however, in the more useful clinical range of 2.0-10.0 ng/ml, the correlation was reduced to 0.923; in the 2.0-6.0 ng/ml range, it was further reduced to 0.852. The slope for the entire range was 0.948; however, in the 2.0- to 10.0-ng/ml range, it was 0.894; in the 2.0- to 6.0-ng/ml range, the slope was 0.815. Using PSA cutoffs of 4.0, 5.0, and 6.0 ng/ml, significant decrease in abnormal PSA values in men with cancer was observed with the IMx compared with Tandem. These data suggest that the IMx and the Tandem PSA assays are not equivalent, and in most patients a lower value is realized with the IMx assay. This bias appears to be greater in men with prostate cancer. Clinicians must be aware which assay their patients are being tested with, and laboratory technicians should run internal standards to ensure lack of significant intralot variability and consistency over time.

Humans↗
PubMed1995

Sialyl-Lewis(x) and related carbohydrate antigens in the prostate.

Alteration of cell surface carbohydrate antigens during malignant transformation is a well-known phenomenon observed in various tumors. In prostatic carcinoma, nearly total deletion of normally occurring ABO and type I-based Lewis antigens, Le(a) and Leb, has been observed in several studies. We studied expression of the closely related type II antigens Le(x), Le(y), and sialyl-Lewis(x) (SLe(x)) using monoclonal antibodies. Thirty formalin-fixed specimens obtained from radical prostatectomy, containing prostatic carcinoma as well as benign tissue, were evaluated by immunohistochemistry. In both cancer and benign tissue, Le(x) expression was minimal or absent. In benign tissue, Le(y) was expressed in ducts and in the basal layer of glandular epithelium. In tumor tissue, Le(y) expression was greatly increased and extensive staining was observed in 26 of 30 cases. The SLe(x) expression in benign tissue was observed only in larger ducts, never in glandular secretory epithelial cells. In carcinoma, rare cells positive for SLe(x) were present in 8 of 30 cases, and stronger expression with focal to patchy distribution was observed in 14 of 30 cases. The results suggest an alteration in glycosyl transferase activity in prostatic carcinoma, with preserved or increased activity of enzymes responsible for the synthesis of the type II core sequence. This sequence is further glycosylated and expressed as the difucosylated compound Le(y) or the monofucosyl, monosialyl compound SLe(x). For prostate, Le(y) and SLe(x) are the only blood group-related antigens known to be minimal or absent in benign secretory epithelial cells that are more highly expressed in malignant tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗
PubMed1995

Measurement of the proportion of free to total prostate-specific antigen improves diagnostic performance of prostate-specific antigen in the diagnostic gray zone of total prostate-specific antigen.

OBJECTIVES: This study examined the clinical significance of non-complexed (free) prostate-specific antigen (PSA) in the differential diagnosis of prostate cancer with an emphasis on patients with total PSA values between 4.0 and 10.0 ng/mL (the diagnostic gray zone). METHODS: Serum samples were obtained from three specimen banks. Patient samples consisted of 55 untreated histologically confirmed primary cancer, 62 men with untreated benign prostatic disease histologically confirmed by 6 negative sextant biopsies, and 64 asymptomatic healthy male controls with normal digital rectal examinations and PSA values less than 4.0 ng/mL. All patients were between the ages of 50 and 75 years. Total PSA levels were determined using the PA immunoassay performed on the TOSOH AIA-1200 automated immunoassay instrument. Free PSA levels were determined using a monoclonal-polyclonal antibody sandwich radioimmunoassay. The proportion of free to total PSA was calculated by dividing the patient's free PSA value by the total PSA value. RESULTS: When all subjects were included, both total PSA and the proportion of free to total PSA significantly differentiated between patients with prostate cancer and patients with benign histologic conditions (P < 0.0001). However, in men with total PSA values between 4.0 and 10.0 ng/mL, the proportion of free to total PSA significantly differentiated between patients with benign and malignant histologic conditions (P = 0.0004), whereas the total PSA did not (P = 0.13). Among this subgroup of patients, the analysis of sensitivity and specificity showed that the proportion of free to total PSA had a clearly higher specificity compared with that of the total PSA at the same level of sensitivity. CONCLUSIONS: Measurement of the free PSA level in a patient's serum and calculation of the proportion of free to total PSA enhances the ability to distinguish benign histologic conditions from cancer while retaining high sensitivity for detecting cancer in men who present with total PSA levels between 4.0 and 10.0 ng/mL. A large-scale population-based study is currently in progress to confirm this preliminary finding.

Aged↗
PubMed1995

Prostate cancer.

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Humans↗
PubMed1995

Variation in measurement of prostate-specific antigen: importance of method and lot variability.

Equivalence between Hybritech Tandem and Abbott IMx PSA methods have been reported by some but not all previous investigators. To determine reasons for these differing conclusions, we measured serum PSA with three different lots each of IMx and Tandem-E kits. Overall, mean IMx results were significantly lower than Tandem-E results; however, for selected sera, the IMx results were consistently higher than the Tandem-E results. Lot-to-lot differences for the IMx method were significantly greater than those with the Tandem-E method. Most IMx/Tandem-E lot-to-lot comparisons had linear regression slopes that differed significantly from 1.0, but some did not. Conclusions concerning the equivalence of the IMx and the Tandem-E methods can be influenced both by variations in the proportions of free PSA in sera in tested populations and by lot-to-lot differences in the IMx method.

Humans↗