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R A Stephenson

Publications and source records attributed to R A Stephenson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Age, genetic, and nongenetic factors influencing variation in serum sex steroids and zonal volumes of the prostate and benign prostatic hyperplasia in twins.

BACKGROUND: We have observed that hereditary and environmental factors have a substantial influence on the plasma content of sex steroids in normal male twins and in men of families with prostatic disease. METHODS: The contribution of genetic and nongenetic familial factors on the variation of plasma sex steroid concentrations and of the volume of zones of the prostate measured by transrectal ultrasound (TRUS) has now been investigated in pairs of male monozygotic (MZ) and dizygotic (DZ) twin pairs between age 25-75 years. Bioelectric impedance permitted quantitation of body fat, lean body mass, and water. Morphometrics and testicular volume were also determined. RESULTS: The intraclass correlation (rI) was > 0.40 for the variation of the total volume (TV), the transition zone (TZ), the peripheral zone (PZ), and the ratio of TZ/PZ in both MZ and DZ twins, and heredity affected 22% of the variation of the PZ and TZ and 30% of the ratio of TZ/PZ. None of the TV and environmental factors influenced the remainder of the variation. Heredity accounted for 25% or more of the variation of dihydrotestosterone (DHT), and the ratios of DHT/testosterone (T), estradiol (E2)/T, androstanediol glucuronide, sex hormone-binding globulin (SHBG)-bound T, T/SHBG, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and dehydroepiandrosterone sulfate (DHEA-S). In MZ twin pairs the variation of the volumes of the prostate became greater with age. In contrast, the variation of the sex hormone concentrations did not show greater variation with age. Heredity also affected > 30% of the variation for waist measurement, weight, body fat, body mass, water and lean body mass, body mass/fat, and testicular size. CONCLUSIONS: Our results indicated that both MZ and DZ twin pairs had zonal prostate volumes more like their twin pair than like unrelated twins. However, nongenetic factors exerted stronger influences than genetic factors on zonal volumes of the prostate. In contrast, hereditary factors had stronger influences on determining the variation of many sex hormones and morphometric characteristics than did nongenetic factors.

Adult↗
PubMed1997

Population-based prostate cancer trends in the United States: patterns of change in the era of prostate-specific antigen.

We reviewed prostate cancer trends prior to and during the prostate-specific antigen (PSA) era using data reported from population-based tumor registries in the United States. On the basis of a summary of reports from several population-based tumor registries, prostate cancer incidence rose abruptly during the PSA era, peaked in 1992, and then fell just as abruptly. Prostate cancer incidence in the United States now appears to be approaching levels seen in the pre-PSA era. The flux in prostate cancer incidence (in both magnitude and slope) during the years 1988-1995 is without precedent in oncology. As expected, an age and stage migration toward early age and early stage has been observed. Unexpectedly, grade has shifted heavily toward moderate differentiation, whereas rates of poorly and well-differentiated disease have remained relatively stable. Local treatment rates, particularly radical prostatectomy rates, have risen substantially. Mortality rates appear to have leveled or declined slightly since 1991 after years of steady rise.

Aged↗
PubMed1997

Prostate size in hypogonadal men treated with a nonscrotal permeation-enhanced testosterone transdermal system.

OBJECTIVES: This study examined the effects of testosterone replacement using a nonscrotal testosterone transdermal (TTD) system on prostate size and prostate-specific antigen (PSA) levels in hypogonadal men. METHODS: As part of an open-label, multicenter study, prostate volume as measured by transrectal ultrasound and PSA were assessed in 29 hypogonadal men during treatment with intramuscular testosterone enanthate (+TE), followed by 8 weeks of androgen withdrawal (-T), and then during 1 year of therapy with Androderm Testosterone Transdermal System, a nonscrotal permeation-enhanced TTD system (+TTD). RESULTS: Mean prostate volume decreased significantly from the +TE period (17 g) compared with the -T period (14 g) (P < 0.001). Prostate volume increased significantly from the -T period compared with the +TTD period (18 g) (P < 0.001). Maximum prostate size, comparable to that measured during +TE (P = 0.125), was reached by month 3 of +TTD therapy; prostate volume did not increase further during the remaining 9 months of +TTD therapy. Prostate volume correlated with age (P < 0.01) during all three periods of observation (+TE: r = 0.69; -T: r = 0.64; and +TTD: r = 0.55). No patient developed symptomatic benign prostatic hyperplasia during the treatment period. PSA levels decreased during androgen withdrawal compared with levels measured during +TE treatment (P < 0.001) and rose with resumption of androgen therapy with TTD (P < 0.006). However, PSA levels during +TTD replacement remained significantly lower (P < 0.001) than during +TE replacement. CONCLUSIONS: Physiologic testosterone replacement in hypogonadal men was achieved using the TTD system. Prostate size during therapy with TTD was comparable to that reported for normal men. In these men treated with TTD, PSA levels were also within the normal range.

Administration, Cutaneous↗
PubMed1997

Effects of age and sex hormones on transition and peripheral zone volumes of prostate and benign prostatic hyperplasia in twins.

Benign prostatic hyperplasia has been shown to increase with age and be influenced by sex hormones. The relationship between aging and hormonal influences on growth of zones of the prostate is unresolved. We studied the relationship of age and sex hormones on volume of prostate zones in 214 male twins between 25 and 75 yr old. Volumes of the total prostate (TV), transition zone (TZ), and peripheral zones (PZ) were measured using transrectal ultrasound, and sex steroid concentrations were measured using RIA. Using transformed data corrected for age, TV (r = 0.54, P < 0.00001), TZ (r = 0.58, P < 0.00001), and PZ (r = 0.39, P < 0.00001) volumes increased with age. However, the PZ volume rose more rapidly than the TZ before age 50, and TZ showed a steeper increase after age 50 yr than the PZ volume. The TZ, PZ, and ratio TZ/PZ correlated significantly (r = 0.87, 0.90, and 0.52, respectively; P < 0.00001). After a TV exceeded 30 g, the rise of the PZ became attenuated, and the slope of the TZ became steeper. Age-adjusted sex hormone concentration was not evaluated in men with larger prostate volumes. Men with American Urological Association symptom scores above 10 had significantly (P < 0.001) larger total prostate volume (TV) and TZ volume, but not PZ volumes, than men with scores below 10. Prostate volumes correlated inversely with age-adjusted serum testosterone (T), dihydrotestosterone, sex hormone binding globulin, and sex hormone binding globulin-bound T concentrations. These results demonstrate that before age 50 yr or before a prostate weight exceeds 30 g, prostate growth may be mainly from enlargement of the PZ and after age 50, the TZ. In addition, elevated T and dihydrotestosterone concentrations do not predispose men to prostate enlargement or symptoms of benign prostatic hyperplasia.

Adult↗
PubMed1997

Wide excision (nonnerve sparing) radical retropubic prostatectomy using an initial perirectal dissection.

PURPOSE: Positive surgical margin rates after radical retropubic prostatectomy are reported to range from 25 to 50% in contemporary series. We report on 53 nonnerve sparing radical retropubic prostatectomies performed with attention paid to extending the margin of attached periprostatic tissue. This was accomplished primarily by initial perirectal release of periprostatic tissues at the level of longitudinal rectal fibers posterior and lateral to the prostate. This perirectal release ensures that maximal quantities of periprostatic tissue will remain with the prostate specimen and will not be attenuated or sheared away at subsequent stages of the procedure. MATERIALS AND METHODS: Pathological material was examined for capsular penetration and surgical margins using transverse whole mount sections of the prostate at 4 to 5 mm. intervals. Patients were followed at regular intervals with physical examinations and serum prostate specific antigen (PSA) determinations. RESULTS: The series consisted of 6, 5, 14 and 28 cases of clinical stages T1b, T1c, T2a and T2b cancer, respectively. Mean PSA was 10.0 ng./ml. and mean Gleason score was 5.9. Capsular penetration was observed in 47 of 53 cases (89%) and positive surgical margins were noted in 7 (13%). With a median followup of 3.61 years 2 patients experienced PSA defined recurrence. CONCLUSIONS: We believe that positive surgical margin rates may be decreased when technical modifications are directed at increasing the amount of periprostatic tissue excised with the surgical specimen.

Follow-Up Studies↗
PubMed1997

Allelic loss detected on chromosomes 8, 10, and 17 by fluorescence in situ hybridization using single-copy P1 probes on isolated nuclei from paraffin-embedded prostate tumors.

We have implemented a reliable new technique for preparing isolated prostate cancer nuclei from paraffin-embedded tissue sections followed by analysis with single-copy fluorescence in situ hybridization (FISH). Our initial validation is described by comparison of our data with fresh prostate tumor tissue and loss of heterozygosity (LOH) studies. We also describe evaluation of 36 previously unstudied prostate cancer patients. Fifteen archival samples were selected from patients who underwent radical prostatectomy in which direct FISH and LOH data were available. Isolated nuclei were prepared and allelic loss was detected on 17q using a single-copy DNA (P1 phage) probe by FISH. A high (80%) concordance was found when comparing isolated nuclei data with 17q results from fresh preparations and LOH studies. We also examined loss at sites on 8p, 10q, and 17q in samples from 36 patients for whom clinical information was available. Loss was found at any of the three loci in 32/36 (89%) of the specimens with specific loss in 53% of the cases at the 8p locus, 33% at the 10q locus, and 61% at the 17q locus. Studies indicate that, as well as providing potential clinical information, isolated nuclei preparations are as reliable as fresh tissue for single-copy FISH studies.

Aged↗
PubMed1996

Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase by nuclear variants of mycophenolic acid.

Structure-activity relationships in the region of the phthalide ring of the inosine monophosphate dehydrogenase inhibitor mycophenolic acid have been explored. Replacement of the lactone ring with other cyclic moieties resulted in loss of potency, especially for larger groups. Replacement of the ring by acyclic substituents also indicated a strong sensitivity to steric bulk. A phenolic hydroxyl group, with an adjacent hydrogen bond acceptor, was found to be essential for high potency. The aromatic methyl group was essential for activity; the methoxyl group could be replaced by ethyl to give a compound with 2-4 times the potency of mycophenolic acid in vitro and in vivo.

Animals↗
PubMed1996

The fall in incidence of prostate carcinoma. On the down side of a prostate specific antigen induced peak in incidence--data from the Utah Cancer Registry.

BACKGROUND: In the 1980s, prostate specific antigen (PSA) came into wide use as a prostate carcinoma screening and detection method in the United States. Following the introduction of PSA, the age-adjusted incidence of prostate carcinoma reported by the Surveillance, Epidemiology, and End Results (SEER) program in the United States rose rapidly (from 84.4/100,000 in 1984 to 163/100,000 in 1991). When an increase in incidence is observed following the introduction of a screening method, a subsequent decrease in incidence may be expected as prevalent cases are removed from the population (a cull effect). Incidence rates may also fall due to factors such as decreased intensity of screening. The Utah Cancer Registry data were examined for a decrease in prostate cancer incidence. METHODS: We tracked age-adjusted prostate carcinoma incidence trends from the population-based Utah Cancer Registry and compared them with rates from the SEER national registry. RESULTS: A rapid and highly correlated rise in prostate carcinoma incidence has been observed in both SEER and Utah incidence rates between 1988 and 1991, the last year for which SEER data are available. In 1992, Utah incidence rates peaked at 236.2 per 100,000. In 1993 and 1994, Utah incidence rates fell to 195.0, and an estimated 164.0 per 100,000, respectively. CONCLUSIONS: Population-based data from the Utah Cancer Registry indicates that the incidence of prostate carcinoma is decreasing rapidly after a similarly rapid increase.

Age Factors↗
PubMed1996

Renal cryoablation in a canine model.

OBJECTIVES: To assess the potential safety and utility of cryoablation for treatment of selected renal tumors in a canine model. METHODS: Ultrasound and direct physical measurements (depth and width) of five cryolesions were compared. Cryolesions were examined histologically in 6 animals, which were killed at 4 hours, 2 days, 1 week, 3 weeks, 6 weeks, and 12 weeks. Mortality/morbidity was assessed in 12 animals over a 1-month interval, where 6 animals received small (approximately 2 cm) cryolesions and 6 animals received large (one third to one half of kidney) cryolesions. Laparoscopic cryoablation was performed in 2 animals. RESULTS: A statistically significant association of physical and ultrasound dimensions was observed (correlation coefficient R = 0.9295; P = 0.0001). Histologic studies in animals killed up to 1 week after cryoablation revealed complete coagulative necrosis within the cryolesion. The boundary transition from normal to complete tissue necrosis occurred in 1 to 2 mm. Animals killed 3 weeks to 3 months after cryoablation revealed progressive organization with granulation tissue, chronic inflammation, hemosiderosis, fibrosis, and contraction of the cryolesion with parenchymal loss. Untreated renal tissue was histologically normal in all kidneys. No mortality or morbidity was detected in the 12 animals followed for 30 days regardless of the size of the cryolesion. Laparoscopic cryoablation was performed successfully in 2 animals without modification of standard laparoscopic methods. CONCLUSIONS: Sonographic, histologic, and laparoscopic data in a canine model suggest that cryoablation may be a safe, feasible, and useful method for treatment of selected renal neoplasms.

Animals↗
PubMed1996

Evidence for a tumor suppressor gene distal to BRCA1 in prostate cancer.

PURPOSE: The breast-ovarian cancer susceptibility gene, BRCA1, has been implicated by both epidemiologic and genetic studies to be involved in prostate cancer. We wished to test the frequency of BRCA1 deletion and that of other markers in the region of proximal 17q in prostate tumor cells. MATERIALS AND METHODS: We used a dual-color fluorescence in situ hybridization (FISH) assay using P1 phage probes for the BRCA1 gene and 3 flanking sites at 17q12-21, as well as a chromosome 17 centromere-specific alpha-satellite probe, to detect deletions in single-cell suspensions and touch preparations from 23 primary clinical stage B prostate tumors and adjacent nontumor prostate tissues. Lymphoblastoid cells and prostate cells from a normal donor were used to determine control loss values. RESULTS: Significant loss (p < 0.05) of at least 1 of the P1s was detected in 16 of 23 (70%) cases, and in 4 of those cases all markers were lost, consistent with whole chromosome loss. Of the 12 cases with subchromosomal loss, 8 had loss distal to BRCA1. Loss was detected in 5 cases previously reported by using allelic imbalance (AI) methodologies, and was detected in an additional 11 non-AI cases, suggesting that FISH is more sensitive than AI for deletion detection in prostate tumor cells. CONCLUSIONS: The data suggest that the region distal to BRCA1 may contain 1 or more prostate-specific tumor suppressor genes and that BRCA1 itself plays only a minor role in prostate cancer development.

BRCA1 Protein↗
PubMed1996

Repair of rectourinary fistulas using a posterior sagittal transanal transrectal (modified York-Mason) approach: an update.

PURPOSE: We report our experience with posterior sagittal, transanal, transrectal repair of rectourinary fistulas. MATERIALS AND METHODS: A total of 16 fistula repairs was done in 15 patients. RESULTS: Of the fistulas 13 occurred after a variety of prostatic procedures, 1 after Y-V plasty and 1 after pelvic trauma (2 repairs were attempted in the latter case). Six patients underwent repair without colostomy. No patient experienced fecal or anal complications and all repairs were successful. CONCLUSIONS: Our surgical approach for repair of rectourinary fistulas is simple, effective, associated with minimal morbidity and cost-effective.

Fractures, Bone↗
PubMed1996

Cellular proliferative fraction of metastatic lymph nodes predicts survival in stage D1 (TxN+M0) prostate cancer.

PURPOSE: We assessed the ability of tumor cellular proliferative fraction to predict long-term survival among patients with lymphatic metastases from prostate cancer. MATERIALS AND METHODS: We studied 50 patients with stage D1 (TxN+M0) prostate cancer who underwent pelvic lymphadenectomy and 125iodine seed implantation between 1970 and 1978. We used the MIB-1 monoclonal antibody to Ki67 to stain sections of the lymphatic metastases in these patients. The Ki67 proliferative fraction was defined as the fraction of positively stained malignant nuclei. We also used flow cytometry to determine the deoxyribonucleic acid content of the lymphatic metastases. RESULTS: Median followup was 6.1 years. Patients whose metastases had a Ki67 proliferative fraction of less than 0.1 had significantly longer survival compared to those with a proliferative fraction of greater than 0.1 (8.7 years versus 4.4 years, respectively, p = 0.005, log rank test). The Ki67 proliferative fraction and ploidy were not independent variables. Patients whose metastases were diploid had a significantly longer survival than those with aneuploid metastases (8.8 years versus 4.4 years, respectively, p = 0.01, log rank test). Multivariate analysis showed that ploidy had a slightly stronger effect on survival than did the Ki67 proliferative fraction. CONCLUSIONS: Cellular proliferative fraction of lymphatic metastases is useful to predict survival in patients with stage D1 prostatic carcinoma. Proliferative fraction may be useful as a marker of progression among patients with other stages of disease.

Biomarkers, Tumor↗
PubMed1996

Does transurethral resection of the prostate compromise the radical treatment of prostate cancer?

Obstructive voiding symptoms are frequent complaints in men with prostate cancer. Some men with prostate cancer require transurethral resection of the prostate (TURP) for relief of these symptoms. Two central questions have been raised regarding whether TURP may have adverse effects on morbidity and mortality in patients with prostate cancer. The first question deals with potential tumor cell dissemination at the time of TURP, resulting increased progression and mortality rates. A review of the literature suggests the risk of tumor dissemination during a TURP is small or negligible. However, patients with prostate cancer and obstructive symptoms appear to have a greater likelihood of high-stage disease at presentation. When the pathological stage is known, progression and mortality outcomes are similar in TURP and non-TURP treated patients with prostate cancer. The second question deals with the potential that TURP increases treatment-related morbidity of radiation therapy or radical prostatectomy. When TURP is required before radiation therapy, the literature suggests that delaying radiation 6 to 8 weeks from the time of the TURP will minimize incontinence and bladder neck contracture to acceptable levels. The literature also indicates that radical prostatectomy may be performed with no increased morbidity following a TURP.

Humans↗
PubMed1995

Loss of chromosome 17 loci in prostate cancer detected by polymerase chain reaction quantitation of allelic markers.

Using a polymerase chain reaction/microsatellite marker system, we demonstrated that 6 of 22 (27%) clinical stage B (early) primary prostate tumors showed loss of heterozygosity at one or more of five loci on chromosome 17. The sensitivity of this study was increased by use of a PhosphorImager and statistical analysis of replicate tumor-normal DNA pairs. Two patients showed tumor-specific interstitial loss at a locus in close proximity to the familial breast cancer gene BRCA1. These findings suggest that genes on the proximal long arm of chromosome 17 play a pivotal role in the early development of at least a subset of prostatic tumors.

Alleles↗
PubMed1995

Effects of age, sex steroids, and family relationships on volumes of prostate zones in men with and without prostate cancer.

Benign prostatic hyperplasia (BPH) and prostate cancer commonly occur together. This suggests that common familial, hormonal, and environmental factors contribute to their development. In men at risk for the development of prostate cancer (at 40 men in 19 families) and aged-matched unrelated controls (n = 46), we have determined whether familial factors, age, and blood hormone concentrations are related to the transition zone (TZ), peripheral zone (PZ), or total volume of the prostate measured by transrectal ultrasound (TRUS). We determined that the influences of age, prostate cancer (n = 15), and familial status did not significantly affect the relationships reported. Therefore, data from all groups were combined for this study. TZ correlated positively with age (P = 0.003) after controlling for family status, but total prostate volume correlated insignificantly with age (P = 0.08). In addition, the ratio of TZ to PZ volumes also correlated significantly with age in the control group (r = 0.27, P = 0.014). Both TZ and PZ volumes correlated highly (r = 0.91, P < 0.0001, n = 86) with total volume. In addition, total volume correlated significantly (r = 0.71, P < 0.001) with the ratio of the TZ/PZ volumes, which also correlated significantly with each other (r = 0.61, P < 0.0001, n = 86). In contrast to the increase of TZ volume related to total prostate volume, PZ volume declined compared with total volume. Prostate volumes up to 50 ml are predominated by the PZ and above 50 ml by the TZ, which may compress and shrink the PZ. Both TZ and total prostate volume correlated positively with serum estrone concentrations (P = 0.04 and P = 0.003, respectively). These results suggest that the risk of prostate cancer does not contribute to generalized overgrowth of the prostate, including the TZ. However, estrogens and age strongly influence TZ but not PZ volume. Both PZ and TZ volumes rise together until the prostate exceeds 50 ml, when the growth of the TZ appears to exceed the PZ and then to compress it.

Aged↗
PubMed1994

Aneusomy of chromosomes 7 and 17 detected by FISH in prostate cancer and the effects of selection in vitro.

Twenty prostate tumor specimens, obtained from radical prostatectomies, and two lymph node metastases were examined by classical and molecular cytogenetic methods. A sample from each tumor was analyzed histologically and used for touch preparations. Adjacent samples were used for preparation of single-cell suspensions before cell culture (DirFISH) and for establishing cell cultures, which were subsequently harvested for classical G-banding analysis. Fluorescence in situ hybridization (FISH) was performed on touch preparations, DirFISH, and cells obtained from tissue culture. Biotinylated pericentromeric probes for chromosomes 7 and 17, in addition to a digoxigenin-labeled X-chromosome probe, were used in a dual-color FISH assay. The results indicated that, in uncultured tumor cells, chromosome 17 was lost in 55% of specimens, chromosome 7 was gained in 16% of specimens, and 9% of specimens showed large tetraploid populations. After cell culture, 23% of specimens showed loss of chromosome 17, no specimens showed gain of chromosome 7, and no tetraploid populations were present. This study suggests that loss of chromosome 17 may play an important role in the development of prostate cancer, and that genetic changes observed after selection in vitro may not represent those in the original tumor.

Aneuploidy↗
PubMed1992

Metastatic model for human prostate cancer using orthotopic implantation in nude mice.

BACKGROUND: Understanding the mechanism of prostate cancer metastasis is essential to the design of a more effective therapy. An effective therapy for this disease will depend on the development of a clinically relevant in vivo model. PURPOSE: We describe the development of such a model by using orthotopic implantation of human prostate cells in BALB/c nude mice. METHOD: We compared the tumorigenicity of and the incidence of metastasis of human prostate cancer PC-3M and LNCaP-FGC (LNCaP) cell lines subsequent to prostatic (orthotopic) or subcutaneous (ectopic) implantations in male nude mice. RESULTS: LNCaP cells produced tumors only in the prostate. Enhanced tumorigenicity at the orthotopic site was found for PC-3M cells. Lymph node metastases were observed in practically all mice given an injection of PC-3M cells in the prostate, but they were uncommon with subcutaneous injection of these cells. Bilateral orchiectomy did not alter the tumorigenicity of either PC-3M or LNCaP cells or the incidence of lymph node metastasis by PC-3M cells. LNCaP tumors in the mouse prostate (but not PC-3M tumors) elaborated detectable levels of human prostate-specific antigen (PSA) in the serum, even when tumors were small (1.5 mm in diameter). Immunohistochemistry analysis revealed the presence of the PSA marker in tissue sections of LNCaP but not of PC-3M tumors. CONCLUSIONS: The implantation of human prostate cancer cells in an ectopic environment does not permit expression of metastatic potential. In contrast, intraprostatic implantation does. IMPLICATIONS: These data suggest that the orthotopic injection of human prostate cancer cells into the nude mouse may provide a valuable model to study the biology and therapy of human prostate cancer.

Animals↗