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M K Brawer

Publications and source records attributed to M K Brawer.

At least 91 records · Page 5Linked to original sources
PubMed1995

Repeat prostate needle biopsy: who needs it?

The indications for repeat prostate needle biopsy after a transrectal ultrasound guided sextant biopsy are not defined. We examined 100 sextant prostate needle biopsies without a diagnosis of malignancy, which were repeated. Carcinoma was detected in 20 repeat biopsies (20%). Stratification based on initial biopsy result revealed carcinoma in 10 of 69 cases (14.5%) without prostatic intraepithelial neoplasia or atypia, 5 of 17 (29.4%) with atypia, 5 of 5 (100%) with grade II or III prostatic intraepithelial neoplasia and 0 of 9 with grade I prostatic intraepithelial neoplasia. Examination of prostate specific antigen (PSA) levels and PSA velocity did not provide statistically significant stratification, perhaps due to the wide variance in these parameters and the small sample size. We conclude that patients with a diagnosis of glandular atypia, or grade II or III prostatic intraepithelial neoplasia on initial biopsy are at high risk for invasive carcinoma and should undergo repeat prostate needle biopsy. A rapidly increasing serum PSA level or grossly abnormal digital rectal examination may also indicate carcinoma not discovered on initial biopsy.

Biopsy, Needle↗
PubMed1994

Predictors of pathologic stage in prostatic carcinoma. The role of neovascularity.

BACKGROUND: Prostate adenocarcinoma is a significant cause of morbidity and mortality in older men. However, the histologic prevalence far exceeds clinically manifest disease. Increased screening has resulted in the detection of a large number of carcinomas of unknown malignant potential. The authors investigated tumor angiogenesis to predict pathologic stage in prostatic tumors. Angiogenesis in prostatic intraepithelial neoplasia (PIN), a putative premalignant lesion, also was investigated. METHODS: Immunohistochemistry was used to highlight the tumor vasculature. Vessels were quantified using computerized image analysis. A minimum of five randomly selected microscopic fields were measured from each tumor. To investigate PIN, the authors measured vessels per millimeter of gland perimeter, compared with benign glands in the same patient. RESULTS: Vessel density (vessels per millimeter squared [vv/mm2]) correlated with pathologic stage. The mean vessel density of organ-confined tumors was 80.2 vv/mm2 (95% confidence interval [CI], 71.4-91.0), compared with 110.4 vv/mm2 (95% CI, 97.9-122.8) for tumors with capsular penetration or positive lymph nodes. Logistic regression analysis and modeling showed vessel density superior to histologic grade and preoperative prostate-specific antigen (PSA) level in distinguishing organ-confined tumors from those having extracapsular extension or pelvic lymph node metastasis. PIN in acini and ductules had increased microvascularity relative to benign epithelium in 18 of 25 tumors (P < 0.05). CONCLUSIONS: Neovascularity has been demonstrated to be a prerequisite for tumor progression. These data demonstrate that microvessel density in prostatic carcinoma is an independent predictor of pathologic stage and, presumably, malignant potential. Quantification of tumor angiogenesis may allow stratification of patients to type of treatment and may allow selection of expectant management for men with low tumor microvessel density.

Adenocarcinoma↗
PubMed1994

How to use prostate-specific antigen.

OBJECTIVE: To determine if prostate-specific antigen (PSA) is the most effective analyte for diagnosing, staging, and monitoring prostatic carcinoma. METHODS: This article reviews what PSA is and how it can be used to detect clinically significant carcinomas as well as its application in managing patients after radical prostatectomy, radiation therapy, and androgen deprivation therapy. RESULTS: PSA screening results in increased detection of localized disease. In individual patients a serum PSA level is not a good indicator of pathologic stage; however, a serum PSA level of greater than 10 ng/mL is associated with a higher incidence of extracapsular disease. Asymptomatic patients with newly diagnosed untreated prostate cancer and a serum PSA level less than 10 ng/mL do not need to undergo staging radionuclide bone scan. Elevated serum PSA is generally the first indicator of "persistent disease" after radical prostatectomy and radiation therapy. In androgen deprivation the PSA nadir is an important indicator of response to therapy. CONCLUSIONS: PSA is the most accurate tumor marker in oncology. This analyte can be successfully used to diagnose, stage, and monitor prostatic carcinoma.

Adult↗
PubMed1994

The significance of isoechoic prostatic carcinoma.

The diagnosis of prostatic carcinoma is most commonly made today by transrectal ultrasound guided needle biopsy. Often hypoechoic and peripheral zone lesions are the only areas sampled. Recently, we showed that this approach missed a quarter of the cancers that would be detected by a systematic biopsy technique. We term these missed cancers isoechoic carcinomas. We reviewed 1,549 systematic sextant prostate needle biopsies, of which 417 cancers were detected and subdivided into hypoechoic cancers (cancers detected on biopsy of a hypoechoic sector and isoechoic cancers (cancers found only in normal [isoechoic] peripheral zone). We noted in men with only isoechoic cancers that fewer biopsy cores per prostate revealed cancer (mean 1.6 versus 3.0, p < 0.0001) and that these men had lower serum prostate specific antigen levels (mean 14.4 versus 43.7, p < 0.001). The Gleason scores for the isoechoic and hypoechoic cancers were indistinguishable. The pathological staging of hypoechoic and isoechoic cancers was also similar. This study suggests that while isoechoic cancers are generally smaller than hypoechoic cancers, they do not represent low grade clinically insignificant carcinomas. A systematic approach to performing prostate biopsy is recommended.

Biopsy, Needle↗
PubMed1994

The Prostate Cancer Intervention Versus Observation Trial: a randomized trial comparing radical prostatectomy versus expectant management for the treatment of clinically localized prostate cancer.

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) is a randomized controlled trial sponsored by the Department of Veterans Affairs and the National Cancer Institute. PIVOT will enroll 2,000 participants from at least 80 Veterans Administration and National Cancer Institute medical centers. The purpose of PIVOT is to determine which of 2 strategies is superior for managing clinically localized prostate cancer (stage T1/T2NXM0) of all histological grades. Patients less than 75 years old will be randomized to either radical prostatectomy with early intervention for disease persistence/recurrence or expectant management with palliative therapy reserved for symptomatic or metastatic disease progression. Participants will be excluded if they have received prior therapy for prostate cancer (except transurethral resection of the prostate) or are judged not to be candidates for radical prostectomy. All patients with newly diagnosed prostate cancer will be recorded on the PIVOT screening log. Registry information will include patient age, race, prostate specific antigen level, clinical stage, histological tumor grade, initial therapy, and vital status. Patients meeting eligibility criteria will watch an information and randomization video tape developed for PIVOT. Participants will be randomized over a 3-year period and followed for a minimum of 12 years. Data collected at followup will include urological symptoms, disease and treatment related morbidity, and disease specific and overall quality of life. Evidence of symptomatic or asymptomatic disease persistence, recurrence or progression will be measured by questionnaire, physical examination, digital rectal examination, prostate specific antigen and annual bone scan. The primary study end point will be all cause mortality. Secondary outcomes will include prostate cancer and treatment specific morbidity and mortality rates, health status, predictors of disease specific outcomes and cost-effectiveness. PIVOT will provide a 90% power to detect a 15% relative decrease in all cause mortality and a 35% relative decrease in prostate cancer specific mortality rate by either treatment strategy.

Aged↗
PubMed1994

Diagnosis of prostatic carcinoma: the yield of serum prostate specific antigen, digital rectal examination and transrectal ultrasonography.

Three tests are commonly used to diagnose prostate carcinoma to date: serum prostate specific antigen (PSA), digital rectal examination and transrectal ultrasonography. We evaluated these 3 tests in 1,001, 6-sector prostate needle biopsies to rule out prostate carcinoma. Of the biopsies 253 (25.3%) revealed prostate cancer. As a single test, PSA was superior to digital rectal examination or transrectal ultrasonography in predicting cancer in this patient population using difference of proportions tests. Receiver operating characteristic analysis also showed PSA to be the superior test. The combinations of PSA plus transrectal ultrasonography and PSA plus digital rectal examination were superior to digital rectal examination plus transrectal ultrasonography. We found cancer in 35 of 188 patients (18.6%) with intermediate PSA levels of 4.1 to 10.0 ng./ml. and normal or asymmetric nonindurated rectal examinations. Only 5 of 79 patients (6.3%) with a normal digital rectal examination and PSA level of less than 4.0 ng./ml. demonstrated carcinoma on biopsy. Of the 5 patients 4 had annual increases in PSA of 40% or greater. While hypoechoic sectors were more than twice as likely as isoechoic sectors of the prostate to contain malignancy on biopsy, nearly 37.6% of the cancers were found in isoechoic sectors. A strategy of performing biopsy of only hypoechoic sectors would have misdiagnosed 24.6% of the patients with prostate cancer. We conclude that serum PSA is the most accurate of the 3 diagnostic tests evaluated. We also recommend a systematic sextant biopsy technique.

Aged↗
PubMed1994

Urinary prostate specific antigen levels after radical prostatectomy.

It was recently demonstrated that urinary prostate specific antigen (PSA) is discordant with serum PSA in many patients after radical prostatectomy. This observation led to the speculation that elevated urinary PSA in the face of undetectable serum PSA may indicate early disease recurrence. We measured urinary PSA levels in 30 patients who had undergone radical prostatectomy for prostate carcinoma and 7 patients who had undergone cystoprostatectomy for bladder cancer. PSA levels of randomly collected urine samples ranged from 0.00 to 22.9 ng./ml. and 0.01 to 8.37 ng./ml., respectively. There was no correlation among urinary and serum PSA levels, pathological stage or type of operation. In 14 patients who had undergone radical prostatectomy and who had measurable levels of urinary PSA voided specimens were divided into initial stream and end stream voided samples. The PSA levels in the end stream voided samples were significantly less than the initial stream sample in 12 of the 14 patients. In men who had undergone radical prostatectomy urethral swab samples were analyzed for PSA. Of 26 patients 24 had detectable levels of urethral swab PSA (range 0.01 to 39.04 ng./ml., median 0.93 ng./ml.). Urethral swab PSA levels did not correlate with serum PSA values or pathological stage of disease. Of 7 patients who had defunctionalized urethras after radical cystoprostatectomy 5 had significantly elevated PSA in the urethral wash or swab samples (range 4.3 to 24.5 ng./ml.). Immunohistochemical analysis of urethrectomy specimens demonstrated positive staining for PSA in 3 of 4 specimens. We conclude that the major source of urinary PSA following total prostatectomy is the urethra itself rather than residual prostate tissue. Measuring serial urinary PSA appears to have limited value in monitoring patients after radical prostatectomy. Whether this urethral PSA can ever contaminate the serum levels of PSA after radical prostatectomy is currently under investigation.

Cystectomy↗
PubMed1994

Morphometric quantitation of stroma in human benign prostatic hyperplasia.

OBJECTIVES: Human benign prostatic hyperplasia (BPH) consists of three major histologic components: stroma, epithelium, and luminal space. For the relief of bladder outlet obstruction caused by BPH, quantitation of the histologic composition of BPH may aid in selecting treatment. To investigate variation between patients in the stromal percentage of BPH, we performed quantitative morphometry on specimens from patients with clinically significant bladder outlet obstruction obtained by three procedures: open prostatectomy, transurethral resection of the prostate (TURP), and prostate needle biopsy (PNB) just prior to TURP. METHODS: Ten specimens obtained by each surgical procedure were analyzed. Specimens were stained with antibody to muscle-specific actin to mark the stroma; quantitation of stroma was accomplished by computer image analysis. RESULTS: The percentage of stroma in all BPH cases ranged from 49.9% to 76.7% (mean, 65.4%, SD = 7.4). No significant difference was observed when comparing samples obtained by the three procedures (p = 0.70). Smooth muscle stromal composition was also quantified in PNB specimens. For these samples, a significant inverse relationship was found between the percentage stroma in the biopsy and the percentage of stroma composed of smooth muscle (r2 = 0.49; p = 0.021). CONCLUSIONS: The data demonstrated that the largest component of BPH was stroma, which comprised approximately 50% to 75% of the total hyperplastic tissue. The mean and range of stromal percentage were similar whether investigating large tissue samples from open prostatectomies or small samples from needle biopsies. PNB data indicated that an increased percentage of stroma may be due to increased nonmuscular elements in the stroma.

Antibodies, Monoclonal↗
PubMed1993

The diagnosis of prostatic carcinoma.

The increased incidence of prostatic carcinoma is the result of several factors including increased awareness among clinicians and the public of the significance of carcinoma of the prostate, the aging of the American population, and improvements in diagnostic methods. Most patients in whom prostatic cancer currently is diagnosed are evaluated because of symptoms of bladder outlet obstruction or abnormalities found by digital rectal examination (DRE). Incidentally detected carcinoma of the prostate on simple prostatectomy specimens (transurethral resection or open) occurs in 10-20% of patients. DRE abnormalities, leading to prostatic needle biopsy, explain most of the remaining diagnoses. Rarely, patients have other signs and symptoms, such as azotemia, weakness, anemia, and bone pain. Needle biopsy of the prostate is performed, generally, in the United States; however, aspiration cytologic examination is used widely in Europe. Ultrasound-guided needle biopsy is gaining increasing utility in many centers, all but replacing digitally guided prostate biopsies. The role of transrectal ultrasonography for diagnosis recently has fallen into some disfavor. Prostate-specific antigen assays represent a potentially important diagnostic test for prostatic cancer; however, its utility in this regard continues to be investigated.

Biomarkers, Tumor↗
PubMed1993

Terazosin in the treatment of benign prostatic hyperplasia. Terazosin Benign Prostatic Hyperplasia Study Group.

OBJECTIVE: To evaluate the efficacy and tolerability of terazosin, a long-acting selective alpha 1-receptor antagonist, in patients with benign prostatic hyperplasia. DESIGN AND SETTING: Randomized, double-blind, multicenter (eight government and private facilities), placebo-controlled study. PATIENTS: Men aged 45 years or older, with qualifying signs and symptoms of benign prostatic hyperplasia (n = 160). INTERVENTIONS: Terazosin or placebo once daily, with terazosin dosage titrated to the patient's response. After a 4-week placebo lead-in, 1 to 10 mg of terazosin or placebo was administered for 24 weeks. OUTCOME MEASURES: Decreases in mean Boyarsky scores for obstructive and irritative symptoms and total scores and increases in peak urine flow rate. RESULTS: Terazosin-treated patients had decreases in Boyarsky obstructive, irritative, and total scores of 3.3 (52%), 1.3 (29%), and 4.6 (42%), respectively, compared with decreases of 0.7 (12%), 0.4 (9%), and 1.1 (11%), respectively, in the placebo group (P < .05). Peak urine flow increased by a mean of 2.6 mL/s (30%) in terazosin-treated patients and 1.2 mL/s (14%) in placebo-treated patients (P < or = .05). Adverse events that differed significantly in the two groups were dizziness (19% in the terazosin group vs 5% in the placebo group) and urinary tract infection (1% in the terazosin group vs 10% in the placebo group). CONCLUSIONS: These results suggest that terazosin given once daily in doses up to 10 mg alleviates symptoms and improves peak urine flow rate in men with benign prostatic hyperplasia and has an acceptable adverse event profile.

Adrenergic alpha-Antagonists↗
PubMed1993

Prostatic intraepithelial neoplasia and prostate-specific antigen.

Prostatic intraepithelial neoplasia (PIN) is a putative premalignant lesion of the prostate gland. PIN has been demonstrated to share morphologic and phenotypic similarities to invasive carcinoma of the prostate. In addition, PIN is spatially related to invasive carcinoma and occurs with greater frequency in men whose prostates harbor carcinoma. Prostate-specific antigen (PSA) is a glycoprotein produced by the prostatic epithelium. For PSA to be detected in the serum, it must traverse several tissue layers to reach the circulatory system. PSA levels associated with PIN are intermediate between those of benign and malignant prostate tissue. Spatially associated occult carcinoma, disruption of the basal cell layer, and increased vascularity may account for elevated PSA values in PIN.

Humans↗
PubMed1993

Comparison of microscopic vascularity in benign and malignant prostate tissue.

A variety of malignant neoplasms have been shown to induce capillary neovascularization, and in some cases the degree of vascularization appears to correlate with aggressive behavior and risk of metastasis. We hypothesized that carcinoma of the prostate also induces the formation of new capillaries, and we developed a method to quantify the relative density of microscopic vessels in carcinoma of the prostate compared with benign prostatic glandular tissue. The number of microvessel profiles in tissue sections was quantified by marking the vascular endothelial cells with antibodies to factor VIII-related antigen using standard immunohistochemistry techniques and comparing fields of adenocarcinoma with benign glandular tissue in 15 radical prostatectomy specimens. The analysis was facilitated by using the Optimas computerized image analysis system (Bioscan, Seattle, WA) with software written for this investigation. Fourteen of the 15 cases demonstrated significantly higher vascular density in the areas of carcinoma than in the benign tissues. Overall, the ratio of vessels per unit area in sections of carcinoma versus benign tissue was approximately double (ratio = 2.02; P < .001). In benign tissues the capillaries are restricted for the most part to the periglandular stroma immediately adjacent to the epithelium, whereas the distribution in carcinoma appears to be more random. The data demonstrate the increased density of capillaries in prostatic carcinoma when compared with benign prostate tissue.

Aged↗
PubMed1993

New technique for repair of rectal injury.

Injury to the rectum is a potentially serious complication of pelvic surgery. The management of rectal injury is controversial. We present a technique of using flaps of endopelvic fascia to reinforce the repair and isolate the injury site. We have utilized this approach in 4 men undergoing retropubic prostatectomy without complications.

Humans↗