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M C Benson

Publications and source records attributed to M C Benson.

At least 55 records · Page 3Linked to original sources

Enhanced reverse transcriptase-polymerase chain reaction for prostate specific antigen as an indicator of true pathologic stage in patients with prostate cancer.

BACKGROUND: As up to 50% of all patients with prostate cancer who have undergone radical prostatectomy are found to be understaged subsequent to surgery, a more sensitive early staging modality currently is needed. A molecular assay that detects prostate specific antigen (PSA)-synthesizing cells in the peripheral circulation of patients with prostate cancer is described. METHODS: An enhanced reverse-transcriptase polymerase chain reaction (RT-PCR) assay specific for PSA mRNA was performed on RNA extracted from blood drawn from 94 patients before radical prostatectomy. Surgical specimens were examined to determine the extent of tumor spread. The assay was compared with imaging modalities, digital rectal examination, and serum PSA level as predictors of pathology. Additionally, patients were monitored postoperatively by serum PSA level to determine any potential correlation between patient RT-PCR scores and subsequent tumor recurrence. RESULTS: Postoperative pathology revealed that 36 of the 94 patients had extraprostatic disease at the time of surgery. Enhanced RT-PCR identified 26 of these patients from preoperative blood specimens (72% sensitivity). The test was negative for 51 of the 58 patients with organ-confined disease (88% specificity). An odds ratio analysis showed that no other preoperative staging modality was related more strongly to extraprostatic or organ-confined disease. Follow-up PSA determinations revealed that RT-PCR positive patients were at higher risk for a recurrence. At 6 months after surgery, the rates for an increased PSA were 19 and 2% for RT-PCR-positive and -negative patients, respectively. CONCLUSIONS: The data from this follow-up study continue to support the utility of enhanced RT-PCR as an early staging modality for radical prostatectomy candidates.

Androgen Antagonists↗

Molecular staging of prostate cancer. II. A comparison of the application of an enhanced reverse transcriptase polymerase chain reaction assay for prostate specific antigen versus prostate specific membrane antigen.

Current imaging modalities used to stage prostate cancer clinically fail to detect extracapsular disease in a significant subset of patients. A molecular based peripheral blood assay using the reverse transcriptase polymerase chain reaction has recently been shown to be a highly sensitive staging modality for detecting extraprostatic disease preoperatively. The assay uses primers that are specific for prostate specific antigen (PSA). We compare the application of the reverse transcriptase polymerase chain reaction assay using primers specific for the human prostate specific membrane antigen with results obtained from the same specimens by reverse transcriptase polymerase chain reaction for PSA. Prostate specific membrane antigen, a recently cloned prostatic antigen, is a transmembrane glycoprotein that has been described as prostate specific. These assays were applied to ribonucleic acids extracted from the peripheral blood lymphocyte fraction of 80 patients with clinically localized prostate cancer. In addition, blood specimens from 20 female patients, 20 young male patients, 25 age-matched control men under treatment for benign prostatic hypertrophy and 20 men with established, untreated metastatic prostate cancer were tested. All 3 groups of noncancer patients had negative polymerase chain reactions for PSA as well as prostate specific membrane antigen. Of 20 metastatic prostate cancer patients 16 (80%) had positive polymerase chain reactions for PSA, while only 10 (50%) had positive results for prostate specific membrane antigen. Among the 80 patients with clinically localized disease (stages T1 to T2cN0M0), 27 and 19 had positive polymerase chain reaction for PSA and prostate specific membrane antigen, respectively, from blood specimens obtained preoperatively. Analyzing the final pathology in each patient with the reverse transcriptase polymerase chain reaction assay identified a significantly stronger correlation with tumor invasion using the results of the PSA test rather than the results of the prostate specific membrane antigen reverse transcriptase polymerase chain reaction test (67% versus 34% sensitivity for detecting capsular penetration, 87% versus 46% sensitivity for detecting disease to the surgical margin and 83% versus 16% sensitivity for detecting seminal vesicle invasion). In contrast to the reverse transcriptase polymerase chain reaction assay for PSA, a similar assay done for prostate specific membrane antigen did not correlate with pathological stage of prostate cancer.

Adenocarcinoma↗

The incidence of multifocal renal cell carcinoma in patients who are candidates for partial nephrectomy.

PURPOSE: A prospective study was performed to determine the incidence of multifocal renal cell carcinoma in patients who are candidates for partial nephrectomy. MATERIALS AND METHODS: Preoperative imaging studies and surgical specimens in 44 patients suitable for partial nephrectomy but undergoing radical nephrectomy were prospectively reviewed. RESULTS: Of 44 renal cell cancers 11 (25%) demonstrated pathological multifocality, while 10 of 11 multifocal tumors (91%) occurred in the face of a primary tumor 5 cm. or smaller. Tumor multifocality was independent of the size of the primary renal tumor but occurred with a slightly higher frequency in tumors of stage T3A or greater even if the primary tumor was small. CONCLUSIONS: Partial nephrectomy in patients with unilateral renal cancer should be approached with caution and should not be performed simply because it is technically feasible.

Adult↗

Prostate specific antigen and prostate specific antigen density. Roles in patient evaluation and management.

Prostate specific antigen (PSA) is the most accurate serum marker for prostate cancer. However, sensitivity and specificity are suboptimal, especially at the intermediate levels between 4.1 and 10.0 ng/ml (monoclonal). For intermediate PSA levels, PSA density (PSAD) provides unique information regarding the need for biopsy and the likelihood of prostate cancer. The authors prospectively used PSAD to determine the need for biopsy in 68 patients with PSAD values below 0.150 and normal results from a digital rectal examination. Ten patients have undergone biopsy secondary to a rising serum PSA. Three were found to harbor prostate cancer and have undergone therapy. The remaining 65 patients continue on surveillance. PSAD can predict treatment outcomes for patients with clinically localized prostate cancer treated with radical prostatectomy. PSADs at low values are 90% accurate in predicting operative success. PSADs at high values are 67% accurate in predicting failure. Cancer 1994; 74: 1667-73.

Biomarkers, Tumor↗

Molecular staging of prostate cancer with the use of an enhanced reverse transcriptase-PCR assay.

OBJECTIVE: Because up to 40 percent of surgically treated patients with prostate cancer are subsequently found to be clinically understaged, a more sensitive staging modality to identify extraprostatic disease prior to surgery is required. METHODS: We describe an enhanced reverse transcriptase [RT] polymerase chain reaction (PCR) assay utilizing oligonucleotide primers specific for the human prostate-specific antigen (PSA). This assay identifies PSA-synthesizing cells from reverse transcribed mRNA. This assay was applied to RNAs extracted from the peripheral blood lymphocytes of 65 patients with clinically localized prostate cancer. In addition, blood from 20 women, 20 young men, 25 age-matched control men under treatment for benign prostatic hyperplasia (BPH), and 18 men with established, untreated metastatic prostate cancer was tested. RESULTS: An RT-PCR assay for PSA can recognize one PSA-expressing cell diluted into one hundred thousand lymphocytes. The sensitivity of this assay can be enhanced by the addition of digoxigenin-modified nucleotides to the PCR reaction and this assay was applied to RNAs extracted from the peripheral lymphocyte fraction of 148 prostate cancer patients and controls at this institution. Although no specimen from women or men without cancer was positive in this assay, 14 of 18 metastatic prostate cancer patients were positive (77.8%). Additionally, 25 of 65 (38.5%) patients with clinically localized disease (T1-2b) were positive from blood specimens obtained prior to surgery. Final pathologic results from this group of patients identified a correlation between positivity on this assay and the presence of capsular tumor penetration (sensitivity, 68%; specificity, 84%) as well as strong correlation with the finding of carcinoma at the surgical margin (sensitivity, 87%; specificity, 76%). Logarithmic regression analysis of the results of the RT-PCR assay indicates its remarkable superiority to digital rectal examination, computed tomography scan, endorectal coil magnetic resonance imaging, PSA, prostate-specific antigen density, or Gleason score for predicting the true pathologic stage of prostate cancer in these surgically treated patients. CONCLUSIONS: An RT-PCR assay using PSA primers to detect prostate cells in the peripheral circulation of surgical-candidate patients is significantly correlated with capsular penetration and tumor-positive surgical margins. This molecular assay provides a sensitive and specific means to stage correctly apparent localized prostate cancer prior to radical prostatectomy.

Adult↗

Predictive value of prostate-specific antigen density for the presence of micrometastatic carcinoma of the prostate.

OBJECTIVE: To examine the efficacy of prostate-specific antigen (PSA) density (PSAD; serum PSA/prostate volume) as a predictor of clinical outcome of patients undergoing radical retropubic prostatectomy for clinically confined prostate cancer, and its ability to determine the presence of micrometastatic disease. METHODS: A retrospective analysis of patient outcome as reflected by surgical stage and postoperative PSA was performed with respect to PSAD as determined by preoperative PSA and pathologic prostate gland volume. The findings for 107 consecutive patients who underwent radical prostatectomy are reported. RESULTS: PSAD at low values was found to be 90 percent accurate in predicting operative success or absence of micrometastatic disease. PSAD at high values was shown to be 70 percent accurate in predicting failure. CONCLUSIONS: PSAD appears to be useful in selecting patients for radical prostatectomy and may be capable of identifying patients with micrometastatic disease.

Biomarkers, Tumor↗

Percutaneous approach to treatment of Indiana pouch stones.

Continent urinary diversions have gained popularity during recent years in the treatment of patients who require cystectomy. The formation of urinary stones remains a possible late complication of urinary diversion. We report the successful use of a percutaneous approach to remove stones from an Indiana pouch after other methods failed.

Combined Modality Therapy↗

Prostate-specific antigen density: a new prognostic indicator for prostate cancer.

PURPOSE: Prostate specific antigen density, previously described as a ratio of serum prostate specific antigen to the volume of the prostate, has been shown to be an important factor in the discrimination of patients with occult metastatic disease and patients with benign versus malignant prostatic disease. We undertook a retrospective study to determine if prostate specific antigen density was a predictor of outcome following definitive conformal radiation therapy. METHODS AND MATERIALS: Between January 1989 and August 1991, 86 patients with localized prostate cancer (confined to the prostate, periprostatic tissue, or seminal vesicles) were treated in the Department of Radiation Oncology, Columbia-Presbyterian Medical Center with definitive radiation therapy using computed tomography-guided conformal technique. Thirteen patients were excluded on the basis of prior prostatectomy, hormonal therapy, or no pretreatment prostate specific antigen measurement. Seventy-three patients were evaluable: 19% (14/73) American Urologic Association Stage A (T1), 41% (30/73) B (T2), and 40% (29/73) C (T3). Prostate specific antigen density was defined as the ratio of the pretreatment serum prostate specific antigen to the prostate volume as determined from computed tomography treatment planning scans. Pretreatment prostate specific antigen density was calculated for each patient and ranged from 0.04-3.85 with a mean and median value of 0.66 and 0.33, respectively. Prostate specific antigen failure was defined as a rise above normal level or, for patients whose nadir was above 4 ng/ml, an increase of greater than 10% above nadir. Mean prostate specific antigen follow-up was 13 months (range 2.3-31 months) by which time 66% of patients had normal prostate specific antigen (< or = 4 ng/ml) levels. RESULTS: Nine patients experienced prostate specific antigen failure. The mean prostate specific antigen density of patients with disease-free survival versus failures was 0.53 and 1.6, respectively (p < 0.05). Kaplan-Meier analysis showed that patients with a prostate specific antigen density < or = 0.3 (n = 30) had 100% actuarial disease-free survival at 30 months compared with 62% for patients with prostate specific antigen density > 0.3 (n = 43, p < 0.01). Patients with a prostate specific antigen density < or = 0.6 (n = 52) and > 0.6 (n = 21) had an 88% and 57% actuarial disease-free survival at > 24 months (p < 0.05). CONCLUSION: Prostate specific antigen density was an excellent predictor of disease-free survival (p < 0.01) and was superior to clinical stage (p > 0.05), Gleason's score (p > 0.05), and pretreatment prostate specific antigen (p < 0.05). These results suggest that patients with low prostate specific antigen density (< or = 0.3), including those with locally advanced clinical stage, high Gleason's score, or elevated pretreatment prostate specific antigen, do well with conventional radiation therapy and should not be subjected to high risk protocols. Further follow-up will be required to determine if patients with low prostate specific antigen density will have improved overall survival.

Aged↗

An algorithm for prostate cancer detection in a patient population using prostate-specific antigen and prostate-specific antigen density.

Prostate-specific antigen (PSA) is the most accurate serum marker for cancer of the prostate (CaP). However, its sensitivity and specificity are suboptimal, especially at values ranging between 4.1 and 10.0 ng/ml (monoclonal), because benign prostatic hypertrophy and hyperplasia (BPH) and CaP frequently coexist in this range. This study was undertaken to determine the value of incorporating prostate volume measurements with serum PSA levels in a quotient (PSA/volume) entitled PSA density (PSAD). A total of 3140 patients were analyzed and stratified by serum PSA, digital rectal examination (DRE), transrectal prostate ultrasound (TRUS), TRUS volume determination and PSAD. All patients were referred for evaluation and therefore do not represent a screened population. Patients underwent prostate biopsies when abnormalities in TRUS or DRE were detected. Although both PSA and PSAD have statistical significance when the serum PSA value is < or = 4.0 ng/ml, neither has clinical significance in differentiating BPH from CaP. At serum levels ranging between 4.1 and 10.0 ng/ml, PSA has no ability to differentiate BPH from CaP, whereas PSAD does so with statistical and clinical significance. When the PSA value is between 10.1 and 20.0 ng/ml, only PSAD is statistically significant. When PSA exceeds 20 ng/ml, PSAD is redundant. We conclude that all patients with an abnormality on DRE or TRUS should undergo prostate biopsy. If the PSA value is < or = 4.0 ng/ml, TRUS and PSAD are not warranted and routine biopsy is not recommended. For intermediate PSA levels, 4.1-10.0 ng/ml, TRUS, TRUS prostate volume, and PSAD are important.2_

Aged↗

PSA density (PSAD). Role in patient evaluation and management.

Prostate Specific Antigen (PSA) is the most accurate serum marker for cancer of the prostate. However, sensitivity and specificity are suboptimal, especially at the intermediate levels between 4.1 and 10.0 ng/ml (monoclonal). For intermediate PSA levels, prostate specific antigen density (PSAD) provides unique information regarding the need for biopsy and the likelihood of prostate cancer. This article summarizes the utility of PSAD in diagnosing and treating prostate cancer.

Aged↗

Toward objective prognostic grading of prostatic carcinoma using image analysis.

At present there is no generally accepted histopathologic grading system for prostatic carcinoma that would be reproducible, and it is still unclear which system provides the most reliable individual prognosis. The objective of this study was to evaluate the relationship between morphometric features and prognosis in patients with clinical stage B prostatic carcinoma using computerized image analysis. Standardized histologic, Feulgen-stained slides from 23 patients operated on for clinical stage B prostatic carcinoma were studied. Dimension-, form- and texture-related nuclear features, both classic and fractal, were computed for at least 100 nuclei per slide. Patients were divided into low-risk and high-risk groups, using as criteria the absence or presence of metastases, respectively, three years after the operation. A discriminant function based on five chromatin texture-related features allowed complete separation between groups with a good or poor prognosis. These preliminary results, however, need to be confirmed on a larger set of patients.

Cell Nucleus↗

Treatment options for upper tract transitional-cell carcinoma.

Nephroureterectomy with a bladder cuff remains the gold standard of treatment of transitional-cell carcinoma of the upper urinary tract. The natural history of the disease, specifically its multifocal nature and its propensity for local recurrence, argues for an aggressive treatment approach. Good clinical results using renal-sparing treatment of low-grade ureteral tumors reveal the feasibility of renal-sparing approaches in limited circumstances. It is likely that, with increasing use of renal-sparing therapy by endoscopic means, topical chemotherapeutic agents will take on an analogous role in the treatment of superficial disease and their role on the treatment of bladder cancer.

Administration, Topical↗

Arteriovenous malformation of ureter.

Congenital arteriovenous malformations of the genitourinary tract are rare. We report the first case of an arteriovenous malformation of the ureter. The patient presented with recurrent hematuria and left flank pain. Evaluation included an intravenous urogram, cystoscopy, and retrograde pyelography. A pedunculated lesion thought to be a fibroepithelial polyp was seen at the time of ureteroscopy, and the lesion treated by excisional biopsy and fulguration. Pathologic examination demonstrated an arteriovenous malformation. After thirty-month follow-up, the patient remains asymptomatic and free of recurrence.

Adult↗

The predictive value of flow cytometry and urinary cytology in the followup of patients with transitional cell carcinoma of the bladder.

To determine the predictive value of flow cytometric deoxyribonucleic acid (DNA) ploidy and urine cytology in patients with superficial transitional cell carcinoma of the bladder, a retrospective analysis was performed on 181 patients who presented for evaluation of presumed superficial transitional cell carcinoma of the bladder. Of the patients 91 were confirmed to have superficial transitional cell carcinoma and were systematically followed with cystoscopy, flow cytometry and urine cytology from 1984 until 1989. They underwent 637 evaluations (mean 7 evaluations per patient). At initial evaluation, flow cytometry had 81% sensitivity and 57% specificity, while urine cytology was 75% sensitive and 94% specific. During the followup flow cytometry was 76% sensitive and 36% specific. Urine cytology was less sensitive (40%) but more specific (81%) than flow cytometry in followup evaluation. These results were similar whether intravesical chemotherapy or bacillus Calmette-Guerin was administered. To ascertain whether false positive flow cytometry represented early detection of recurrent transitional cell carcinoma not apparent at cystoscopy, patients with positive flow cytometry and urine cytology were followed longitudinally. False positive flow cytometry and urine cytology were equally predictive of recurrent transitional cell carcinoma progressively with time. However, for any given examination flow cytometry was more likely to detect and predict recurrent transitional cell carcinoma. At 4 years the bladder transitional cell carcinoma incidence for false positive flow cytometry and urine cytology was 87% and 84%, respectively.

Adult↗

Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer.

Isolated prostate specific antigen (PSA) determinations in asymptomatic individuals have not demonstrated sufficient sensitivity and specificity to be useful in the routine evaluation of prostate disease. To enhance the accuracy of serum PSA we have used a quotient of serum PSA and prostate volume, which we refer to as prostate specific antigen density (PSAD). Prostate volume in this study was calculated from magnetic resonance imaging determinations of benign prostatic hypertrophy (BPH) or from the dimensions of the surgical specimen of cancer using the formula, length x width x depth x 0.5 = volume. A total of 61 patients with prostatic disease clinically confined to the prostate glands (41 with prostate cancer undergoing radical prostatectomy and 20 with BPH) was evaluated. The mean PSAD for prostate cancer was 0.581 while that for BPH was 0.044 (p less than 0.002). No patient with BPH had a PSAD of greater than 0.117 and only 1 patient had a density of 0.1 or greater. Of 34 patients with a PSAD of 0.1 or greater 33 had prostate cancer. Only 2 of the 41 prostate cancer patients and 14 of the BPH patients had a PSAD of 0.05 or less. There were 11 patients with a PSAD of greater than 0.05 and less than 0.1, including 6 with prostate cancer (1 with P0 disease) and 5 with BPH. Of the 6 prostate cancer patients 5 had a PSA of 4.0 or less and among the 5 patients with BPH 4 had a serum PSA of greater than 4.0 and 1 had a PSA of greater than 10. These results suggest that PSAD may be useful in distinguishing BPH and prostate cancer.

Antigens, Neoplasm↗

The use of prostate specific antigen density to enhance the predictive value of intermediate levels of serum prostate specific antigen.

Prostate specific antigen (PSA) is an extremely valuable tumor marker. However, its use in detection is limited by its low positive and negative predictive values. The ability of serum PSA to distinguish between benign and malignant prostatic conditions is particularly poor in the intermediate range of 4.1 and 10 ng./ml. by the Hybritech assay. We used transrectal ultrasound determined prostate volumes in a well characterized population of 533 men to form a serum PSA/prostate volume ratio called prostate specific antigen density (PSAD). The prevalence of cancer in the entire population was 18.4%. Discriminant analysis according to negative or positive outcome allowed for the construction of nomograms, which resulted in a PSAD defined cancer risk ranging from 3 to 100%. Predictive value nomograms created from PSAD may allow for a more individualized approach to evaluation of patients with intermediate levels of Hybritech serum PSA.

Aged↗