Search PubMed⌕ Search

Biomedical subjects

M K Brawer

Publications and source records attributed to M K Brawer.

At least 109 records · Page 6Linked to original sources
PubMed1993

Screening for prostatic carcinoma with prostate specific antigen: results of the second year.

Prostate specific antigen (PSA) has been shown to be useful alone and in conjunction with other tests in the diagnosis of prostatic carcinoma. Previously, we demonstrated that a PSA level of greater than 4.0 ng./ml. as the initial diagnostic test in a screening population results in a detection rate of 2.6 and positive predictive value of 30.5. In the present investigation we performed digital rectal examination and transrectal ultrasound as well as ultrasound guided biopsy in men who in the initial year of the screening study had a PSA level of less than 4.0 ng./ml. but on evaluation 1 year later they had a 20% increase in the PSA level. A total of 701 subjects returned for year 2 of the protocol and 260 (37.1%) demonstrated more than a 20% increase in PSA value. Biopsy was performed in 82 men and carcinoma was detected in 14 (17.1%). Of the men with carcinoma 12 had a second year PSA level of less than 4.0 ng./ml. Radical prostatectomy was performed in 8 patients, 7 of whom had organ confined disease or tumor penetrating the capsule with negative margins. We conclude that a 20% annual change in PSA level may identify men at significant risk for prostatic carcinoma and that patients so identified have favorable pathological stage.

Aged↗
PubMed1993

The inability of prostate specific antigen index to enhance the predictive the value of prostate specific antigen in the diagnosis of prostatic carcinoma.

The prostate specific antigen (PSA) level has become an important but imperfect means of detecting prostatic carcinoma. PSA index (serum PSA normalized to estimated gland volume) has been suggested to improve the performance characteristics of PSA alone. In an attempt to confirm this observation, we compared serum PSA alone to the PSA index in 218 men undergoing systematic random prostatic needle biopsy. Total gland PSA index as well as nontransition zone PSA index were calculated using several constants for the estimated contribution to the serum PSA from the transition zone. The Mann-Whitney nonparametric analysis was performed to account for differences in variances within the data set. For the patient population as a whole, all methods of testing were approximately equivalent in the ability to provide a statistically significant (p < 0.01) stratification between patients with benign and malignant biopsies. In patients with a serum PSA level of 4.1 to 10.0 ng./ml. none of the tests was able to distinguish those with carcinoma from those with a benign biopsy. In men with a normal prostate on digital rectal examination serum PSA was superior to other tests in predicting biopsy results. We conclude that PSA index does not enhance the ability of serum PSA alone to predict the presence of carcinoma.

Aged↗
PubMed1993

The enhanced detection of persistent disease after prostatectomy with a new prostate specific antigen immunoassay.

Prostate specific antigen (PSA) determinations after radical prostatectomy are valuable in detecting persistent disease. Previously, we determined that 0.4 ng./ml. PSA was a reliable clinical threshold using the Hybritech Tandem-R PSA assay. Recently, we reported that a new PSA immunoassay (Abbott IMx PSA) correlated well with results of the Tandem-R immunoradiometric PSA assay and had a lower threshold. Using a conservative threshold of 0.1 ng./ml. PSA for the IMx PSA assay, we analyzed IMx PSA values in serial postoperative serum from 72 radical prostatectomy patients whose initial Tandem-R levels were less than 0.4 ng./ml. PSA. The lower detection limits of the IMx PSA assay allowed approximately a third (15 of 42) more detection of persistent disease within 8 months of surgery. When the PSA level remained undetectable for more than 8 months but the disease eventually recurred the lead times averaged 9 to 12 months when 0.1 ng./ml. PSA was used to signify persistent disease. All patients whose PSA levels reached 0.1 ng./ml. PSA and were subsequently followed for more than 3 months continued to have increasing levels. Also, every man who eventually had recurrence also had a PSA serum level of at least 0.1 ng./ml. PSA within 28 months postoperatively, although the subsequent increase from 0.1 to 0.4 ng./ml. PSA sometimes took several years. Although the clinical impact of these findings is yet unknown, new or altered PSA assays with lower detection limits can provide unique information that may offer opportunities for improved clinical investigation and possibly patient management.

Humans↗
PubMed1993

PSA in benign prostatic hyperplasia and prostatic intraepithelial neoplasia.

Prostate specific antigen has become an important adjunct to the digital rectal examination in screening for prostate cancer. The clinician should be familiar with interpretation of this test. Many men with BPH have elevated serum PSA concentrations; however, the majority of these men will have other pathologic processes such as occult cancer, PIN, or acute inflammation that may account for the elevations in serum PSA. Certainly, serial increases in serum PSA should increase concern that occult carcinoma is present. Patients with PIN may also have elevated PSA concentrations. When PIN is associated with elevated PSA, a high incidence of invasive carcinoma is noted on subsequent biopsy. Further investigation into the associations will further refine the clinical utility of this powerful tumor marker.

Aged↗
PubMed1992

Prostatic intraepithelial neoplasia: a premalignant lesion.

Putative premalignant changes in the prostate have been recognized for a number of years. A variety of synonyms have been given to the most commonly described lesion, characterized by proliferation and dysplasia of the normal two cell layers lining prostatic acini and ductules; prostatic intraepithelial neoplasia (PIN) is the term most often used. A premalignant prostatic lesion should have morphologic features similar to invasive carcinoma (CA), a spatial association with microinvasive cancer arising from the lesion, and should occur at a greater frequency, severity and extent in organs harboring CA. Most definitively, progression from the premalignant lesion into CA should be observed over time. PIN fulfills all but the last of these requirements. High grade PIN is cytologically indistinguishable from prostate carcinoma (CAP). The major differentiating feature between PIN and CAP is the presence, although frequently disrupted, of the basal cell layer in the former. We have studied the basal cell layer in PIN using antibodies to high molecular weight cytokeratins and have found a correlation between PIN grade and the percent disruption of the basal cell layer. The cells making up PIN are phenotypically similar to those of CAP. We have used a variety of markers including cytokeratins, vimentin and the lectin Ulex euroapaeus to demonstrate this similarity. Additionally, we and others have noted decreased PIN immunoreactivity with antibodies directed against prostate specific antigen (PSA) and prostatic acid phosphatase. Other investigators have noted additional phenotypic similarities between PIN and CAP, including the ABH and Lewis antigens. PIN incidence and grade correlate well with the presence of CAP elsewhere in the prostate.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma↗
PubMed1992

Quantitative morphometric analysis of the microcirculation in prostate carcinoma.

Many neoplasms have been shown to induce capillary neovascularization and this may correlate with aggressive behavior. We investigated the phenomenon of neovascularity in benign and malignant prostatic tissue. Microvessel profiles and tissue sections were visualized by antibodies to Factor VIII and standard immunohistochemical techniques, and quantified utilizing the Optimas computerized image analysis system. Microvessel density was compared in benign and cancerous portions of 15 radical prostatectomy specimens. Fourteen of 15 cases demonstrated significantly higher vascular density in the area of carcinoma as compared with benign tissue (ratio = 2.02, p < 0.001). Distribution of microvessels within malignancy was random, whereas it was restricted primarily to the periglandular space in benign tissue. Among 20 men undergoing radical retropubic prostatectomy, there was a correlation between the vessel density and the pathologic stage. No patient with organ-confined carcinoma or cancer penetrating (but not perforating) the capsule had microvessel density greater than 156 microvessels/mm2. In contrast, six of 15 men with more advanced pathologic stage exceeded this arbitrary threshold. These data demonstrate both increased vascularity of prostatic carcinoma as compared with benign tissue, and a further correlation between pathologic stage and vascularity. Microvessel density may be useful as a prognostic indicator.

Humans↗
PubMed1992

Prostate cancer tumor location as predicted by digital rectal examination transferred to ultrasound and ultrasound-guided prostate needle biopsy.

The advent of transrectal ultrasound (TRUS) and the Biopty instrument (Bard Urologic) has revolutionized prostate biopsy (PNB). Theoretically the systematic multiple biopsy approach offers the advantage of less sampling error with respect to presence of carcinoma, grade of carcinoma and sites of tumor within the gland. These parameters may be important in selecting the therapeutic approach and, if radical prostatectomy is contemplated, in modifying the operation as indicated based on tumor location. In the present investigation, we received specimens obtained from 100 men with clinically localized prostatic carcinoma who had previously undergone ultrasound-guided systematic random biopsy (TRUSPNB) along with TRUS and digital rectal exam (DRE). Among the 372 sectors with carcinoma identified in the 100 radical prostatectomy specimens, significant underrepresentation by TRUSPNB was noted (39% false negative). When an abnormality on either DRE, TRUS or TRUSPNB was observed, the sensitivity was 65%. The specificity was 89% when all three tests were abnormal. It would appear that preoperative assessment of tumor location is inadequate with the current modalities available. There may, however, be subsets of patients which would benefit by tumor location utilizing DRE, TRUS and TRUSPNB.

Biopsy, Needle↗
PubMed1992

Prostatic intraepithelial neoplasia: a premalignant lesion.

Putative premalignant changes in the prostate have been recognized for a number of years. A variety of synonyms have been given to the most commonly described lesion, one characterized by proliferation and dysplasia of the normal two cell layers lining prostatic acini and ductules. Currently, "prostatic intraepithelial neoplasia" (PIN) is the term most commonly used to describe this entity. In this review, the requirements for a premalignant lesion, the reason why PIN fulfills the majority of these requirements, and a detailed description of the morphologic and phenotypic similarities between PIN and carcinoma will be outlined. Finally, the clinical significance of PIN will be reviewed.

Humans↗
PubMed1992

Screening for prostatic carcinoma with prostate specific antigen.

Prostate specific antigen (PSA), neutral serine protease secreted exclusively by prostatic epithelial cells, has a number of applications in the management of men with prostatic carcinoma. While it is widely recognized that elevated PSA correlates with the presence of carcinoma, little data exist regarding the use of PSA as the initial test in the early detection of prostatic cancer. We measured serum PSA levels in men older than 50 years and performed digital rectal examination and ultrasound guided prostate biopsy of those who had a PSA level of greater than 4.0 ng./ml. A total of 1,249 men entered the protocol, of whom 187 (15.0%) had PSA levels above 4.0 ng./ml. Digital rectal examination and ultrasound guided biopsy were performed at our facility in 105 patients (56.2%). A total of 32 carcinomas (30.5%) was detected, including 23 in men with PSA between 4.1 and 10.0 ng./ml. and 9 in men with a PSA of greater than 10.0 ng./ml. Of the 32 carcinomas 12 (37.5%) occurred in men with normal prostates or glands demonstrating only asymmetry on digital rectal examination, and 3 men had carcinoma despite normal digital rectal examination and no hypoechoic peripheral zone lesion detected on ultrasound. Of the 32 patients 30 had clinically localized carcinoma but 7 of the 16 undergoing radical prostatectomy had pathological upstaging. We conclude that PSA represents an important adjunct to digital rectal examination for the early detection of prostatic carcinoma. The efficacy of this or any other early detection test to decrease prostate cancer mortality necessitates the results of prospectively randomized clinical trials.

Aged↗
PubMed1992

What will replace TURP?

Benign prostatic hyperplasia (BPH) is almost ubiquitous. About 25% to 40% of men in their lifetime will undergo treatment for BPH. Surgical therapy produces in excess of 400,000 prostatectomies a year at a cost of more than 4 billion dollars. Given the magnitude of the clinical problem and its overall impact on health care in the United States, the interest in alternatives to transurethral resection of the prostate (TURP) is intense. From the panoply of contenders, the panel nominates those most likely to succeed.

Adrenergic alpha-Antagonists↗
PubMed1991

Expression of metalloproteinase genes in human prostate cancer.

Twenty-five surgical specimens of malignant human prostate, 3 lymph nodes with metastatic prostate carcinoma, 11 normal human prostates, as well as 3 human prostate cell lines (DU-145, PC3 and LNCaP) were examined for the expression of the human matrix metalloproteinase-7 gene (MMP-7) from the human collagenase family (originally called PUMP-1 for putative metalloproteinase-1) [Quantin et al. (1989) Biochemistry 28:5327-5334; Muller et al. (1988) Biochem J 253:187-192; Matrisian and Bowden (1990) Semin Cancer Biol 1:107-115]. Northern blots were prepared using total RNA extracted from 18 prostate adenocarcinomas, 2 lymph nodes with metastatic prostate carcinoma and 11 normal human prostates. When the northern blots were hybridized with a 32P-labeled MMP-7 cDNA probe, a 1.2-kb mRNA was detected in 14 out of 18 prostate adenocarcinomas, 1 out of 2 metastatic lymph nodes, and 3 out of 11 normal prostates. The 3 human prostate cell lines did not show any evidence of the MMP-7 transcript. In situ hybridization was conducted to localize the MMP-7 mRNA to individual cells using a 35S-labeled MMP-7 cRNA. In situ hybridization was carried out on snap-frozen tissue sections of 7 prostate adenocarcinomas and 3 lymph nodes containing metastatic prostate adenocarcinoma using the same tissues previously probed by northern analysis as well as new samples. In situ hybridization revealed that the MMP-7 gene was expressed in the epithelial cells of primary prostate adenocarcinoma as well as in invasive and metastatic cells. MMP-7 expression was also seen focally in some dysplastic glands but not in stroma. Additional northern blot analysis was performed using probes to human type-IV collagenase, type-I collagenase and stromelysin I in human prostate adenocarcinoma as well as normal prostate tissue. Our results indicated that 6 out of 10 adenocarcinoma samples and none of the 4 normal samples were positive for type-IV collagenase transcripts. Tissue samples were also examined for the expression of type-I collagenase (9 adenocarcinomas and 4 normal) and stromelysin I (13 adenocarcinomas) by northern analysis. None of the tissues was found to express the transcripts of interest at detectable levels. These data suggest that certain metalloproteinases are present in prostatic adenocarcinoma and may play a role in invasion and metastasis.

Adenocarcinoma↗
PubMed1991

Prostatic abscess after transrectal ultrasound guided biopsy.

We report a case of a diabetic man who had bilateral prostatic abscesses after ultrasound guided biopsy of the prostate. As is typical of prostatic abscesses, the diagnosis was not evident at presentation. We discuss the morbidity of transrectal biopsy and recommend consistent antimicrobial prophylaxis. We also recommend transrectal ultrasound in the diagnosis of such abscesses, and support the standard treatment of drainage and parenteral antimicrobial therapy. We anticipate that the incidence of prostatic abscess will increase due to the increasing number of men undergoing transrectal biopsy in the current age of transrectal ultrasound guided biopsy.

Abscess↗
PubMed1991

Significance of prostatic intraepithelial neoplasia on prostate needle biopsy.

Prostatic intraepithelial neoplasia (PIN) is a putative premalignant change in the human prostate. Previously, the spatial association of PIN with invasive carcinoma has been described in the study of total prostatectomies. PIN is frequently recognized in prostate needle biopsy specimens in which no carcinoma is apparent. To further define the potential significance of PIN, we performed repeat ultrasound-guided prostate needle biopsy in 21 men who had PIN identified on prostate biopsy performed because of an abnormal finding on digital rectal examination. Twelve patients (57%) had carcinoma identified on their second procedure including all who had intermediate- and high-grade PIN on the initial procedure. Prostate-specific antigen correlated with PIN grade and carcinoma on the secondary procedure, although this did not achieve statistical significance. Men with PIN on prostate needle biopsy should undergo repeat sampling to exclude missed carcinoma.

Adenocarcinoma↗
PubMed1991

Morphonuclear relationship between prostatic intraepithelial neoplasia and cancers as assessed by digital cell image analysis.

Using digital cell image analysis performed on Feulgen-stained nuclei, the nuclear characteristics of prostatic neoplasia, ranging from benign (benign prostatic hyperplasia [BPH]), through dysplastic (prostatic intraepithelial neoplasia [PIN] 1-3), to carcinoma were studied. Four histopathologic groups were studied: group IA (18 samples) contained BPH, PIN 1, and PIN 2 lesions that were from 9 prostate samples free of cancer. Group IB (23 samples) was identical to group IA, contained also BPH, PIN 1, and PIN 2 lesions, but lesions that were from 7 prostate samples where malignant foci were detected elsewhere. Group II (11 samples) were PIN 3 specimens. Group III (24 samples) were carcinomas. Features of neoplastic nuclei were quantified objectively through morphometric (nuclear size), densitometric (nuclear DNA content), and textural (chromatin organization and heterogeneity) parameters. Cell kinetic parameter, i.e., cell proliferation index, was assessed from the densitometric measurement. The proliferation index was significantly higher in PIN 3 and cancers as compared to BPH, PIN 1, and PIN 2 tissues. Morphonuclear characteristics were also dramatically distinct among the four groups. Indeed, the nuclear size and the hyperchromatism of severe prostatic dysplasia were similar to those of carcinomas, these two lesion types showing mean parameter values that were higher as compared to BPH, PIN 1, and PIN 2 lesions. Finally, benign tissues related to mild or moderate dysplasia taken in histologic material in which cancer was present already share the morphonuclear characteristics of severe dysplasia, although they are nonproliferating.

Cell Nucleus↗
PubMed1991

Prostate specific antigen. A review.

Despite its identification in the 1970s, prostate specific antigen (PSA) has only recently gained widespread utility. In this review, we will describe significant aspects of the biochemistry of PSA, immunohistochemical applications, the effect of prostatic manipulation on the serum level of this analyte, and other considerations in the determination of the level of PSA. In addition, the effect of benign prostatic hyperplasia (BPH) on serum PSA will be described. Finally, the application of PSA in the detection, staging and monitoring of patients with prostatic carcinoma will be discussed.

Antigens, Neoplasm↗