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C A Olsson

Publications and source records attributed to C A Olsson.

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

Preoperative reverse transcriptase polymerase chain reaction for prostate specific antigen predicts treatment failure following radical prostatectomy.

PURPOSE: We previously demonstrated than an enhanced reverse transcriptase-polymerase chain reaction assay for prostate specific antigen (PSA) can predict final pathological stage in radical prostatectomy patients. The potential role of the assay in predicting serum PSA recurrence after radical prostatectomy was explored. MATERIALS AND METHODS: We evaluated 100 radical prostatectomy candidates by reverse transcriptase polymerase chain reaction preoperatively, and status was compared to serum PSA, Gleason score and final pathological results. Potential surgical failure was defined as tumor at the surgical margin or extending into the seminal vesicle. Patients were monitored postoperatively by serum PSA every 4 months. Kaplan-Meier analysis was used to evaluate the correlation between reverse transcriptase polymerase chain reaction and disease recurrence, defined as a PSA of 0.2 ng/ml. or greater. RESULTS: Enhanced reverse transcriptase polymerase chain reaction for PSA had a stronger correlation with potential surgical failure than preoperative serum PSA or Gleason score (relative risks 15.2, 5.9 and 3.2, respectively). The correlation between these modalities and PSA recurrence was evaluated during a mean followup of 13.6 months (range 5 to 26). Of 36 patients with positive reverse transcriptase polymerase chain reactions 9 had failure by PSA compared to 3 of 64 (4.7%) with negative polymerase chain reactions (p<0.0286). The relative risk for failure by reverse transcriptase polymerase chain reaction was 3.6. Gleason score and serum PSA had higher correlations with postoperative PSA elevations (relative risk 13.2 and 7.6, respectively). A Cox regression analysis model demonstrated that reverse transcriptase polymerase chain reaction for PSA can be used in conjunction with Gleason score and provides statistically significant risk information. CONCLUSIONS: Enhanced reverse transcriptase polymerase chain reaction for PSA is a statistically significant predictor of potential failure by pathological analysis and of disease recurrence by PSA. Longer followup data are required to define further the role of the assay in the management of patients with prostate cancer.

Aged↗
PubMed1996

The ileal ureter neobladder is associated with a high success and a low complication rate.

PURPOSE: Several different methods to construct a bladder substitute after cystectomy have been described. We evaluated our experience with the Studer ileal ureter neobladder during the last 5 years. MATERIALS AND METHODS: We reviewed retrospectively the results in 32 patients who underwent construction of a slightly modified ileal neobladder from that originally described. Mean followup was 25 months (range 6 to 68). RESULTS: Patients experienced few complications and only 1 required reoperation. Daytime and nighttime continence rates were 94 and 74%, respectively. One patient sustained a ureteral stricture resulting in hydronephrosis (1 of 64 renal units). CONCLUSIONS: The results reveal the ileal neobladder to be an easily constructed pouch with a low complication rate, and a high success rate in regard to continence and the establishment of adequate capacity at low pressure. Within the study period upper tract preservation was excellent. However, a 10 to 15-year followup is indicated to confirm our initial results.

Adult↗
PubMed1995

Identification of the human prostatic carcinoma oncogene PTI-1 by rapid expression cloning and differential RNA display.

Elucidating the relevant genomic changes mediating development and evolution of prostate cancer is paramount for effective diagnosis and therapy. A putative dominant-acting nude mouse prostatic carcinoma tumor-inducing gene, PTI-1, has been cloned that is expressed in patient-derived human prostatic carcinomas but not in benign prostatic hypertrophy or normal prostate tissue. PTI-1 was detected by cotransfecting human prostate carcinoma DNA into CREF-Trans 6 cells, inducing tumors in nude mice, and isolating genes displaying increased expression in tumor-derived cells by using differential RNA display (DD). Screening a human prostatic carcinoma (LNCaP) cDNA library with a 214-bp DNA fragment found by DD permitted the cloning of a full-length 2.0-kb PTI-1 cDNA. Sequence analysis indicates that PTI-1 is a gene containing a 630-bp 5' sequence and a 3' sequence homologous to a truncated and mutated form of human elongation factor 1 alpha. In vitro translation demonstrates that the PTI-1 cDNA encodes a predominant approximately 46-kDa protein. Probing Northern blots with a DNA fragment corresponding to the 5' region of PTI-1 identifies multiple PTI-1 transcripts in RNAs from human carcinoma cell lines derived from the prostate, lung, breast, and colon. In contrast, PTI-1 RNA is not detected in human melanoma, neuroblastoma, osteosarcoma, normal cerebellum, or glioblastoma multiforme cell lines. By using a pair of primers recognizing a 280-bp region within the 630-bp 5' PTI-1 sequence, reverse transcription-PCR detects PTI-1 expression in patient-derived prostate carcinomas but not in normal prostate or benign hypertrophic prostate tissue. In contrast, reverse transcription-PCR detects prostate-specific antigen expression in all of the prostate tissues. These results indicate that PTI-1 may be a member of a class of oncogenes that could affect protein translation and contribute to carcinoma development in human prostate and other tissues. The approaches used, rapid expression cloning with the CREF-Trans 6 system and the DD strategy, should prove widely applicable for identifying and cloning additional human oncogenes.

Adult↗
PubMed1995

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↗
PubMed1995

Effect of demographic factors, urinary peak flow rates, and Boyarsky symptom scores on patient treatment choice in benign prostatic hyperplasia.

OBJECTIVES: To determine the effect of patient's age, race, Boyarsky score, and urinary flow rate on type of treatment selected for benign prostatic hyperplasia (BPH) and to evaluate maintenance of treatment at 1-year follow-up. METHODS: Subjects in this prospective study, conducted in a referral center prostate clinic, were 174 consecutive patients, aged 67.6 +/- 10.8 years (mean +/- SD), with previously untreated BPH. Patients underwent structured interviews and uroflowmetry, then completed the Boyarsky Symptom Index. Blinded to these data, one physician described four treatment categories in a nonjudgmental fashion, always using the same order: watchful waiting; finasteride and alpha-blocker; thermal therapy, balloon dilation, and a prostate stent; and transurethral prostate resection. Treatment choice was entirely that of the patient. Independent variables were patient's age, race, symptom score, and uroflow; the dependent variable was treatment choice. At 1 year, the same physician interviewed patients to evaluate maintenance of therapy. RESULTS: Only symptom score and flow rate were predictive of treatment choice, high scores and low flow being associated with more aggressive treatment choices (P = 0.001). Most patients, regardless of symptom severity, chose interventions less aggressive than surgery and more aggressive than watchful waiting. At 1 year, 85% of patients continued to be maintained on their original treatment. CONCLUSIONS: Men with mild or moderate BPH prefer interventions of moderate aggressiveness; race and age make little or no difference. If maintenance of treatment indicates patient satisfaction, most patients appear to remain satisfied with therapy they select.

Adult↗
PubMed1995

Laser tissue soldering in urinary tract reconstruction: first human experience.

OBJECTIVES: Laser tissue soldering (LTS) in the urinary tract provides an immediate leak-free seal and may avoid complications seen with conventional repair (such as fistula and stricture). We have begun a Phase I clinical trial investigating the use of LTS in performing urologic reconstructive surgery. METHODS: Ten patients (aged 3 months to 38 years) underwent urologic reconstruction using LTS with a protein solder composed of human albumin (42%) and indocyanine green dye. In each case standard microsuture repair preceded laser-soldered suture line reinforcement. Anastomotic closure time and immediate leak pressure were measured. Postoperatively, all patients were evaluated for evidence of complications, including stricture, fistula formation, or impaired healing. RESULTS: Using LTS as an adjunct to suturing added an average of 7.9 +/- 3.0 minutes (28%) to the overall mean anastomotic time of 28.3 +/- 9.4 minutes. Intraoperative leak pressure measurements for laser-soldered anastomoses (> or = 94.2 +/- 24.2 mm Hg) were significantly higher (P < 0.001) than primarily sutured anastomoses (20 +/- 2.9 mm Hg). Two instances of suture disruption (20%) occurred during laser activation, neither of which were repaired with sutures. Average follow-up for all patients was 7.1 + - 2.2 months. There were no intraoperative or postoperative complications, including the 2 patients with suture disruption. CONCLUSIONS: These initial clinical results indicate that LTS is safe, easy to perform, and, contrary to conventional suturing, provides an immediate leak-free closure. Follow-up in these and other patients, as well as those undergoing sutureless and stent-free procedures, will determine whether our method of LTS benefits patients undergoing urologic reconstruction.

Anastomosis, Surgical↗
PubMed1995

Terazosin and doxazosin in normotensive men with symptomatic prostatism: a pilot study to determine the effect of dosing regimen on efficacy and safety.

In this pilot study, the effect of dosing schedule on the efficacy and safety of the long-acting alpha 1-adrenergic blockers, terazosin (TER) and doxazosin (DOX), was evaluated in 43 consecutive normotensive men (mean age 59.6 years) with symptoms of prostatism. Patients were randomized to one of four treatment groups: (1) TER 5 mg once in the morning (AM; n = 10), (2) TER 5 mg once in the evening (PM; n = 11), (3) DOX 4 mg once AM (n = 11), and (4) DOX 4 mg once PM (n = 11). Patients were titrated to their final dose over 3 weeks. Parameters evaluated included Boyarsky symptom score (Sx), peak uroflow (Qmax), blood pressure and occurrence of adverse events. Once stabilized, patients were seen at 3-month intervals; follow-up ranged from 4 to 17 months (mean 9.7). Clinical improvement as determined by Sx and Qmax was similar for all four treatment groups. Mean decreases in Sx at 3 months were 4.6, 5.4, 4.9, and 5.0 for TER-AM, TER-PM, DOX-AM, and DOX-PM, respectively. Mean peak uroflow increased 3.0, 3.1, 2.8, and 3.1 ml/s for TER-AM, TER-PM, DOX-AM, and DOX-PM, respectively (p < 0.05 vs. baseline). Eight patients (18%) were withdrawn from the study because of adverse events (fatigue 1, asthenia 1, headache 3, dizziness 4): 5 during the titration phase (TER-AM: 2, DOX-AM: 2, TER-PM: 1) and 3 during the treatment phase (TER-AM: 2, DOX-AM: 1). In these 8 patients, the mean decreases in sitting and standing blood pressure were approximately 7/5 and 10/8 mm Hg, respectively. These data suggest that efficacy of TER and DOX was similar at the dosages employed and not affected by the dosing schedule. Adverse events in this small population were significantly decreased (p < 0.05) by dosing in the PM. These preliminary results suggest that a larger prospective study is warranted to determine (1) the comparative efficacy of TER and DOX in the treatment of symptomatic benign prostatic hyperplasia and (2) optimal timing of the medication.

Adrenergic alpha-Antagonists↗
PubMed1995

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↗
PubMed1995

Transition zone index as a method of assessing benign prostatic hyperplasia: correlation with symptoms, urine flow and detrusor pressure.

PURPOSE: Prostate volume has been poorly correlated to various parameters used to assess benign prostatic hyperplasia (BPH), including symptoms, peak urine flow and detrusor pressure at peak urine flow. The purpose of this study was 2-fold: 1) to determine if transrectal ultrasound measurement of the transition zone of the prostate served as a better proxy for determining prostate size and correlated better with American Urological Association symptom score, peak urine flow and detrusor pressure, and 2) if the parameter transition zone index (the ratio between transition zone volume and prostate volume) was useful in evaluating clinical prostatism. MATERIALS AND METHODS: We prospectively evaluated 61 men with symptomatic BPH (age 64.6 +/- 9.7 years) according to symptoms, peak urine flow, pressure/flow analysis, transrectal ultrasound volume of the entire prostate and the transition zone, and calculation of the transition zone index. RESULTS: Age correlated with symptoms (r = 0.31, p = 0.01) and peak urine flow correlated negatively with symptoms and age (p = 0.002). Age also correlated with prostate volume (r = 0.54 and p = 0.03) and transition zone (r = 0.31, p = 0.05). There was a weak correlation between prostate volume and symptoms, peak urine flow and detrusor pressure at peak urine flow; a stronger correlation between transition zone and symptoms (r = 0.48, p = 0.03), and peak urine flow (r = -0.34, p = 0.05), and a significant correlation (p = 0.001) between transition zone index and symptoms (r = 0.75), peak urine flow (r = -0.71) and detrusor pressure at peak urine flow (r = 0.43). A transition zone index of greater than 0.50 was a useful cutoff point and highly significant (p = 0.002) for delineating patients with more severe abnormalities of symptoms, peak urine flow and detrusor pressure at peak urine flow. CONCLUSIONS: Transition zone index is a parameter that correlates significantly with evaluated parameters of BPH and may serve as a useful proxy for evaluating worsening obstruction. Studies are underway to determine if transition zone index can be used prospectively to predict and correlate response with therapies designed to ablate prostatic tissue medically or surgically.

Age Distribution↗
PubMed1995

Urology peer review at the National Institutes of Health.

PURPOSE: Urology is a field with many subspecialties and, as a consequence, urological research grant applications are distributed to a variety of different study sections at the National Institutes of Health (NIH). It has long been the conviction of urological investigators that urological grant funding suffers as a result of this distribution. We investigated the composition of these study sections to identify the prevalence of urological expertise (or lack thereof). The review challenges the concept that urological research grant applications are being subjected to adequate peer review. MATERIALS AND METHODS: Aided by personnel from the National Institute for Diabetes, and Digestive and Kidney Diseases, and the National Cancer Institute, 22 study sections to which urological grants are distributed were identified. A 3 to 5-year retrospective MEDLINE analysis of all the scientific publications of each study section member was done. Urological experts were identified by the criterion of having more than 1 urological publication published per year or a proportional equivalent. An equivalent analysis was performed for the study sections reviewing cardiology grants to serve as a comparison. RESULTS: Data analysis revealed that only 12 of 351 study section members reviewing urological grants are urological experts (3.4%). Only 3.1% of the collective published productivity of these members is in the broadly defined field of urological investigation. Omitting the published productivity of these 12 experts, less than 1% of the published works of the remaining 339 members reflects interest or expertise in urological investigations. Of the 22 study sections only 8 have urological expertise represented in their membership. Except for 1 study section, representation of urological experts was usually limited to 1 individual reflecting a 5.9 to 11.1% minority in these study sections. CONCLUSIONS: The lack of urological expertise represented on the NIH study sections reviewing basic and clinical urological research grant applications has far reaching ramifications. Consequently, grant applications on genitourinary diseases that commonly afflict a preponderance of Americans are inadequately reviewed at the NIH. Only through the provision of appropriate peer reviewers will this problem be solved.

National Institutes of Health (U.S.)↗
PubMed1995

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↗
PubMed1995

Urodynamics and the etiology of post-prostatectomy urinary incontinence: the initial Columbia experience.

Post-prostatectomy incontinence is a disabling disorder. Urodynamic studies in 56 patients with post-prostatectomy incontinence were reviewed to determine its etiology. Of the patients 31 had undergone transurethral prostatectomy and 25 radical retropubic prostatectomy. After careful history and neurourological examination, uroflowmetry, post-void residual determination and synchronous multichannel video pressure/flow studies were done. The most common etiology for incontinence was detrusor instability alone, which was present in 34 patients (61%), including 24 (77%) after transurethral resection of the prostate and 10 (40%) after radical retropubic prostatectomy. Stress incontinence alone was present in only 3 patients (5%), including 1 (3%) after transurethral resection of the prostate and 2 (8%) after radical retropubic prostatectomy. Detrusor instability with stress incontinence was present in 19 patients (34%), including 6 (19%) after transurethral resection of the prostate and 13 (52%) after radical retropubic prostatectomy. Of these 19 patients 4 (21%) had poorly compliant bladders. This study demonstrates that stress incontinence alone is a relatively rare cause of post-prostatectomy incontinence, with detrusor instability present in more than 90% of the patients. Accurate diagnosis of post-prostatectomy incontinence etiology could ensure proper treatment for this disorder.

Aged↗
PubMed1994

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↗
PubMed1994

Surface-epitope masking: a strategy for the development of monoclonal antibodies specific for molecules expressed on the cell surface.

BACKGROUND: Producing monoclonal antibodies against specific targets, including tumor-specific antigens, is a tedious and extremely inefficient process. PURPOSE: Our purpose was to determine whether DNA transfection combined with an immunologic masking tactic could be used to efficiently generate hybridomas that secrete monoclonal antibodies. The quest was for monoclonal antibodies that would react with molecules existing on the surface of genetically altered cells. METHODS: We developed a masking technique called surface-epitope masking (SEM). The SEM procedure involves the selective blocking of surface antigens present in a genetically engineered cell (referred to as a "tester") with high-titer polyclonal antibodies that have been produced against the untransfected parental cell (referred to as a "driver"). Surface-epitope-masked tester cells were injected into BALB/c mice; immune spleen cells then taken from these mice were fused with myeloma cells. RESULTS: This process resulted in the efficient generation of hybridomas that secreted monoclonal antibodies that reacted with cell-surface antigens on transfected tester cells and with additional cell types that expressed the same surface molecules. In one case, CREF-Trans 6 cells were engineered to express a typical multidrug-resistant (MDR) phenotype. Using CREF-Trans 6:MDR cells as a tester cell line, we utilized the SEM procedure to produce monoclonal antibodies that displayed surface reactivity to both CREF-Trans 6:MDR cells and MDR human breast carcinoma (MCF7) cells. In a second case, human prostatic carcinoma CREF-Trans 6 cells, which were DNA transfected and derived from nude mouse tumors, were used as the tester cell line. The SEM procedure was again used to produce monoclonal antibodies. These antibodies were designed to and did react with: (a) tumor-associated antigens on the surface of the original LNCaP cell line used to obtain human prostatic carcinoma DNA, (b) primary and secondary nude mouse transfectants derived from tumors, and (c) two additional human prostatic carcinoma cell lines, DU-145 and PC-3. CONCLUSIONS: The SEM approach was used for the efficient and selective development of monoclonal antibodies that react with cell-surface molecules with both known and unknown functions. IMPLICATIONS: The SEM procedure should be useful in producing monoclonal antibodies and identifying genes associated with important cellular processes, including immunologic recognition, tumorigenesis, metastasis, atypical multidrug resistance, and autoimmune diseases.

Animals↗
PubMed1994

Rapid construction of right colon pouch: initial clinical experience.

Between December 1992 and July 1993, 7 patients who underwent urinary diversion after cystectomy or bladder augmentation had colon pouches constructed with an "absorbable" staple. Our "one-step" technique of colon pouch construction incorporates standard principles of bowel detubularization and refashioning using absorbable GIA staples. The technique is easily learned and decreases operative time and blood loss. Herein we report follow-up of the first 7 patients undergoing this modification.

Adolescent↗
PubMed1994

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↗
PubMed1994

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↗