Search PubMed⌕ Search

Biomedical subjects

A W Partin

Publications and source records attributed to A W Partin.

At least 199 records · Page 11Linked to original sources
PubMed1994

Concordance rates for benign prostatic disease among twins suggest hereditary influence.

OBJECTIVES: The etiology of benign prostatic hyperplasia (BPH) is unknown. Evidence for a hereditary trait would provide new avenues for investigation. METHODS: We compared the concordance for benign prostate disease in monozygotic (MZ) and dizygotic (DZ) twins who served in the United States military in World War II and have been followed by the Medical Follow-up Agency, Institute of Medicine of the National Academy of Sciences. Questionnaires completed in 1985 by 10,000 twins were reviewed for evidence of prostatic disease. Key words indicating benign prostatic disease (prostate, prostatectomy, BPH, TURP, and prostatism) were identified in 533 (5.3%) of the questionnaires. RESULTS: The average age was 64 +/- 3 years (range 56 to 68 in 1985). After eliminating men with known prostate cancer, there were 256 twin pairs that were informative for benign prostatic disease: both twins were concordant in 25 instances and discordant in 231, with only one twin mentioning benign prostatic disease. The pairwise concordance for MZ twins was 14.7% (19 of 129) and for DZ pairs it was 4.5% (5 of 112). The relative risk for benign prostatic disease for MZ twins was thus 3.3 (p = 0.008). The probandwise concordance rates, which express the probability of BPH in a cotwin of an affected twin, were 25.7% for MZ twins and only 8.5% for DZ twins. A covariance analysis estimated that 49% of the observed variance between twins could be attributed to genetic effects. CONCLUSIONS: These data provide preliminary evidence for the heritability of benign prostatic disease.

Aged↗
PubMed1994

Quantitative nuclear morphometry, Markovian texture descriptors, and DNA content captured on a CAS-200 Image analysis system, combined with PCNA and HER-2/neu immunohistochemistry for prediction of prostate cancer progression.

One hundred and twenty-four localized prostate cancer patients operated on at Johns Hopkins Hospital (JHH) since 1975 were identified. The sample was optimized for evaluation of prostate cancer progression. Based upon accurate clinical histories, these radical prostatectomy patients included 50 progressors and 74 non-progressors using appearance of serum PSA as an indication of recurrence (mean follow-up = 8.6 +/- 1.8 years, range 7-15 years). All patients included in the study had no involvement of their seminal vesicles or lymph nodes at the time of prostatectomy. Average time to progression was 3.6 +/- 2 years, range of 1-8 years. Using paraffin-embedded specimens, several five micron sections were cut and placed on Probe-On slides; one slide was H&E-stained and the other was Feulgen-stained. The H&E and Feulgen-stained slides were screened and "dotted" by pathologists at JHH and CytoDynostics, Inc. A CAS-200 Image analysis system (Cell Image Systems, Elmhurst, IL) equipped with a Cell Measurement Program version 1.2 beta, was used to capture the Feulgen-stained images and to perform the calculations. From the "dotted" areas, 150 cancer cells were selected for measurement of DNA content and 27 nuclear morphometric shape and size factors, including 21 Markovian chromatin texture variables. Additional sections were used for immunochemistry staining with an alkaline phosphatase streptavidin-biotin complex stain to detect and quantitate cancer cells binding monoclonal antibodies directed against proliferating cell nuclear antigen (PCNA) and HER-2/neu antigen. All data were entered into a statistical program (STATA) for further analysis and univariate and multivariate statistical analysis was performed using logistic regression and its stepwise variant. The biomarkers of greatest utility to detect progressors when analyzed univariately included post-operative Gleason score (p = < 0.0001), HER-2/neu antigenicity (p = 0.0147), CAS-200 DNA ploidy (p = 0.008), and twelve Markovian nuclear texture and shape features (p = < 0.0001), whereas PCNA (p = 0.160) failed. The optimal set of nuclear morphometry progression tumor features were selected using backward stepwise logistic regression estimate analysis which drops variables due to collinearity. Although post-operative Gleason score is a strong univariate predictor of progression, DNA ploidy and HER-2/neu contributed significantly to further stratification of higher risk groups within the low Gleason score subpopulation. The best Markovian features combined with post-operative Gleason score generated sensitivity = 90%, specificity = 96%, positive predictive value = 94%, negative predictive value = 93% and the area under the receiver operator curve was 0.975.

Biomarkers, Tumor↗
PubMed1993

Association of glyceraldehyde-3-phosphate dehydrogenase expression with cell motility and metastatic potential of rat prostatic adenocarcinoma.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression is increased in Dunning R-3327 rat prostatic adenocarcinoma cell lines relative to normal rat ventral prostate tissue. GAPDH expression closely correlates with cell motility of Dunning prostate cancer cell lines and accurately distinguishes cell lines with high metastatic potential from those with low metastatic potential. Increased GAPDH expression in the cancer cell lines is not simply related to increased growth rate, since rapidly proliferating normal prostate tissue did not exhibit elevated GAPDH expression.

Adenocarcinoma↗
PubMed1993

Nuclear matrix protein patterns in human benign prostatic hyperplasia and prostate cancer.

The nuclear matrix represents the structural component of the nucleus that determines nuclear shape and higher order DNA organization. We have previously shown tissue specificity in nuclear matrix proteins (NMP), in rat sex accessory tissues, and in a rat model of prostate cancer. This study compares NMP patterns for fresh human normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer for 21 men undergoing surgery for clinically localized prostate cancer or BPH. NMP patterns were compared using high resolution two-dimensional polyacrylamide gel electrophoresis. We identified by molecular weight and isoelectric point 14 different proteins that were consistently present or absent among the various tissues. One protein (PC-1), a M(r) 56,000 protein with an isoelectric point of 6.58, appeared in 14 of 14 different nuclear matrix preparations from prostate cancer and was not detected in normal prostate (0 of 13) or BPH (0 of 14). The NMP patterns are consistent with a model of disease progression in which BPH shares many of the nuclear matrix changes observed in prostate cancer.

Antigens, Nuclear↗
PubMed1993

The use of nuclear morphometry to predict prognosis in pediatric urologic malignancies: a review.

Wilms tumor, the most common pediatric urologic malignancy, and genitourinary rhabdomyosarcoma, the most common soft tissue sarcoma of childhood, represent two of the most commonly diagnosed pediatric urologic malignancies. The introduction and use of multimodal therapy (surgery, radiation, and chemotherapy) by the National Wilms Tumor Study (NWTS) and the Intergroup Rhabdomyosarcoma Study (IRS) groups have greatly improved the survival among children with these malignancies. Present survival rates for Wilms tumor exceed 85% and for rhabdomyosarcoma survival rates are approaching 80% as well. For Wilms tumor, current treatment trends suggest less intense therapy for those children with favorable histology tumors who are considered at relatively low risk for tumor recurrence. Likewise, the significant morbidity associated with the present therapy regimens for rhabdomyosarcomas has prompted investigators to search for individualized management schemes for children with a high probability of responding. The need for accurate criteria to separate these high and low risk groups becomes imperative. In this review we present our work using nuclear morphometry, as a prognostic indicator, to retrospectively predict response to therapy for children with Wilms tumors and genitourinary rhabdomyosarcomas.

Adolescent↗
PubMed1993

The influence of finasteride on the volume of the peripheral and periurethral zones of the prostate in men with benign prostatic hyperplasia.

To determine the influence of androgen deprivation induced by the potent 5 alpha-reductase inhibitor finasteride on the volume of the zones of the prostate, 20 symptomatic men with established BPH were randomized to one of three groups: placebo, finasteride 1 mg, and finasteride 5 mg/day. The volume of the entire prostate gland, periurethral zone, and peripheral zone and the seminal vesicles were determined by three dimensional reconstructions of magnetic resonance contoured images of the prostate. There was no significant difference between the results achieved with 1 and 5 mg of finasteride per day; thus the results in these two groups were combined. In the placebo group there was no significant change in the volume of any structure. Following treatment for 1 year with finasteride there was a significant (P < 0.02) 17% decrease in total gland size (11.5 +/- 3.2 cc). Similarly, there was a significant (P < 0.02) 17% decrease in total gland size (11.5 +/- 3.2 cc). Similarly, there was a significant (P < 0.03) decrease in the size of the periurethral zone of the prostate (6.2 +/- 3 cc). Although there was also a decrease in the size of the peripheral zone of the prostate (2.8 +/- 1.2 cc) this did not reach statistical significance. There was no significant change in the volume of the seminal vesicles. These findings indicate for the first time that androgen deprivation induces a significant decrease in the size of the periurethral zone of the prostate in men with established BPH.

5-alpha Reductase Inhibitors↗
PubMed1993

Relationship between changes in prostate-specific antigen and prognosis of prostate cancer.

Changes in prostate-specific antigen (PSA), used to estimate PSA doubling times, may reflect prostate cancer growth. To determine if PSA doubling time prior to diagnosis predicted outcome in men with prostate cancer, we evaluated 16 men with prostate cancer who had (1) serial PSA determinations (mean 9.9) on frozen sera from twelve to twenty-six years before diagnosis; (2) at least five years of follow-up in those subjects without metastatic disease (range 5.5-12.3 years); and (3) archival material from diagnosis available for pathologic evaluation. PSA doubling time prior to diagnosis was investigated with relation to patient outcome (regardless of treatment) and the known predictors of tumor behavior, Gleason score and nuclear morphometry. In 5 of 16 men who had evidence of metastatic disease at diagnosis, metastasis developed or they died of prostate cancer during follow-up (group 1). Eleven of 16 had no evidence of metastatic disease during follow-up (group 2). Both Gleason score and variance of nuclear roundness (VNR) were significantly greater for group 1 (p < 0.05). There was no significant difference between the two groups with respect to PSA doubling time, and the PSA level at diagnosis did not correlate with the development of metastatic disease. One of 5 men with no PSA level greater than 4.0 ng/mL prior to diagnosis died within two years of diagnosis. These data suggest that (1) a normal PSA at diagnosis does not exclude an aggressive cancer, and (2) changes in PSA that occur before the diagnosis of prostate cancer may not always predict outcome. Since PSA level is influenced by tumor grade, an inability to correct PSA for tumor grade could have influenced the results.

Aged↗
PubMed1993

Nuclear morphometry accurately predicts recurrence in clinically localized renal cell carcinoma.

Despite careful clinical staging, as many as 30 percent of patients with pathologically, specimen-confined renal cell carcinoma (RCC) have unpredictable recurrence following surgery. Present pathologic and clinical staging systems cannot accurately predict those patients with high risk of disease recurrence from those who are cured by surgery alone. Advances in immunotherapy including gene therapy for RCC have dictated the need to identify RCC patients for adjuvant therapy protocols who have a high probability of recurrence following nephrectomy. Nuclear morphometric techniques developed at our institution have predicted prognosis for a variety of genitourinary tumors; it was used to predict recurrence among patients undergoing nephrectomy for localized RCC. This report is a retrospective study of 26 patients with RCC of similar age, stage (pT1-pT3), and grade. Fifteen were free of disease at a mean of 75.2 months, and 11 had distant disease recurrence at a mean of 27.1 months. Statistical analysis of a variety of nuclear shape descriptors accurately separated this group of patients based on disease recurrence. No nuclear shape descriptor predicted disease recurrence when nuclei within the region of the tumor with the highest grade were analyzed. However, the range of nuclear ellipticity (p = 0.007) best predicted disease recurrence when nuclei were selected in a random fashion. Multivariate analysis of the four best shape descriptors better predicted disease recurrence (p = 0.002) with a sensitivity of 73 percent and specificity of 100 percent. These results are encouraging and suggest that this technique might be used in identifying patients for adjuvant gene therapy.

Adult↗
PubMed1993

The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer.

Clinical stage, Gleason score and serum prostate specific antigen (PSA) levels are used separately to predict pathological stage in patients with localized prostate cancer. Because the degree of tumor differentiation has a profound influence on the expression of serum PSA, serum PSA levels alone do not reflect tumor burden accurately. To overcome this obstacle we tested these 3 variables alone and in combinations as predictors of final pathological stage in 703 men with clinically localized prostate cancer at our institution. All patients were assigned a clinical stage by 1 urologist. The Gleason score was determined from preoperative needle biopsy and serum PSA levels were measured on an ambulatory basis. Final pathological stage was determined to be either organ confined, established capsular penetration, seminal vesicle involvement or lymph node involvement. Logistic regression analysis with the likelihood ratio chi-square test determined that serum PSA, Gleason score and clinical stage all predicted final pathological stage well. The results were improved with combinations of the 3 variables (serum PSA, Gleason score and clinical stage) and the combination provided the best separation. From these analyses probability plots and nomograms have been constructed to assist urologists in the preoperative prediction of final pathological stage for patients with clinically localized prostate cancer.

Biomarkers, Tumor↗
PubMed1993

Influence of wide excision of the neurovascular bundle(s) on prognosis in men with clinically localized prostate cancer with established capsular penetration.

We analyzed 107 men with clinically localized prostate cancer who had pathologically established capsular penetration in the region of the neurovascular bundles to determine the effect of wide excision of the neurovascular bundle(s) on disease-free survival. In 38 patients established capsular penetration was not suspected clinically and the neurovascular bundle(s) were preserved. In 69 patients established capsular penetration was suspected, and 1 or both neurovascular bundles were excised widely with the prostate. Disease-free survival was defined by an undetectable serum prostate specific antigen (PSA) level postoperatively. Wide excision of the neurovascular bundle(s) resulted in negative surgical margins in 40 of 69 patients (58%) compared to only 17 of 38 (45%) in whom the neurovascular bundle(s) was left intact (p = 0.03). Median interval to disease recurrence, as defined by a measurable serum PSA level, was 22 months in the group in whom the neurovascular bundles were preserved versus 33 months in the group undergoing wide excision (p = 0.03). At 39 months, however, 70% of the patients in both groups had detectable PSA levels. Similarly, patients with positive surgical margins had a mean interval to recurrence of 17 months compared to 38 months for the group with negative surgical margins (p = 0.0004). By 43 months, however, 75% of the patients in both groups had a detectable PSA level and the Kaplan-Meier curves had converged. Although wide excision of the neurovascular bundle(s) resulted in negative surgical margins more often with resultant delayed disease progression, most patients with established capsular penetration ultimately failed radical prostatectomy despite wide excision of periprostatic soft tissue. It seems likely, therefore, that many of these patients have occult metastatic disease at operation. Thus, recent enthusiasm for radical prostatectomy in men with locally advanced prostate cancer may not be justified.

Adenocarcinoma↗
PubMed1993

The use of nuclear morphometry in predicting recurrence of transitional cell carcinoma.

Despite apparently adequate surgical resection, metastases develop in about 50% of the patients who undergo radical cystectomy for invasive bladder cancer and they die of disease within 2 years of surgery. Recent reports have shown that combination chemotherapy with regimens including cisplatin results in significant improvement in time to progression and overall survival for patients with transitional cell carcinoma. We have used quantitative nuclear morphometry in an effort to predict which individual patients with muscle invasive transitional cell carcinoma are at increased risk for recurrence and in need of adjuvant therapy. A total of 14 patients with deeply invasive tumors without known metastases (tumors, nodes and metastasis stage P3A-B, N-, M0) who had not received perioperative radiation or systemic chemotherapy was studied. Of the patients 7 (group 1) had no evidence of disease with a mean followup of 41 months and 7 (group 2) had recurrent transitional cell carcinoma at a mean followup of 17 months. Both groups were similar with respect to age and could not be distinguished by standard pathological analysis of stage (p = 0.66) or grade (p = 0.99). A total of 150 tumor nuclei from each patient was digitized and analyzed by a high resolution quantitative morphometric imaging system, developed in this laboratory, to determine if nuclear shape descriptors could separate these 2 clinically distinct groups. A multivariate analysis combining 3 independent nuclear shape descriptors (average nuclear area, minimum feret-diameter ratio and kurtosis of feret-diameter ratio) was highly significant (p = 0.003) and separated patients in group 1 from group 2 without overlap. These encouraging results suggest that nuclear morphometry may be valuable in determining which patients are at increased risk of disease recurrence following radical cystectomy and, therefore, who should receive adjuvant chemotherapy.

Aged↗
PubMed1993

Is tumor volume an independent predictor of progression following radical prostatectomy? A multivariate analysis of 185 clinical stage B adenocarcinomas of the prostate with 5 years of followup.

Tumor volume has been shown to be proportionate to Gleason grade, capsular penetration, seminal vesicle invasion, lymph node metastases and capsular margins of resection. Because these variables are often interrelated, it is crucial to determine which of these parameters provides independent prediction of prognosis in prostate cancer. The current study analyzed 185 men who underwent radial retropubic prostatectomy for clinical stage B adenocarcinoma of the prostate. Patients with seminal vesicle invasion or lymph node metastases were excluded, since these findings are almost invariably associated with progression. All patients were followed for a minimum of 5 years after radical prostatectomy. Only 2 men received postoperative adjuvant therapy. At 5 years after radical prostatectomy 58 men (31%) experienced progression, defined by either an elevated postoperative serum prostate specific antigen level, local recurrence or distant metastases. Although by themselves capsular penetration, tumor volume and per cent of the prostate involved by tumor predicted progression, in a stepwise regression analysis they did not provide independent prognostic information. In this multivariate analysis Gleason score was the best predictor of progression (p < 0.0001); surgical margin was the only other variable that enhanced prediction, although it was less influential than grade (p = 0.018). This strong predictability provided by Gleason score was all the more impressive given the relatively few patients in our study with either low or high grade tumor. Although an accurate preoperative assessment of tumor volume remains desirable for the management of patients with prostate cancer, our study demonstrates that measurement of tumor volume in radical prostatectomy specimens need not be performed as part of the routine pathological analysis of radical prostatectomy specimens, since it does not provide additional information beyond that of Gleason score and the status of capsular margins.

Adenocarcinoma↗
PubMed1993

Serum PSA after anatomic radical prostatectomy. The Johns Hopkins experience after 10 years.

1. With an average follow-up of 53 months (range 12-120 months), 19.4% (185/955) of men have had a cancer recurrence after radical prostatectomy for clinically localized prostate cancer. A detectable serum PSA was the only evidence of recurrence in 11.2%, whereas 2.2% have had a recurrence locally and 6% with distant metastases. 2. The actuarial status at 10 years was 70% for undetectable serum PSA; 23% for isolated serum PSA elevation only; 7% for distant metastases; and 4% for local recurrence. 3. In our study, no patient demonstrated disease progression (local or distant) without detectable serum PSA. 4. The actuarial likelihood of an elevated serum PSA increased with increasing clinical stage, Gleason score, preoperative serum PSA concentration, and pathologic stage. 5. The actuarial recurrence rate for tumors with a Gleason score of 7 was not statistically different from the recurrence rate for lesions of Gleason score 8-10. 6. There exist marked differences in actuarial recurrence-free probabilities for men with tumors of low Gleason score (< 7) compared with those with tumors of high Gleason score (> or = 7) when there is pathologically established capsular penetration. 7. Patients with preoperative serum PSA concentrations greater than 10.0 ng/mL are at a statistically increased risk of recurrence. 8. Men who have detectable serum PSA within the first year after surgery are at a significantly higher risk of disease progression than those men who have measurable serum PSA in postoperative years two and three. 9. Men with an isolated elevation of serum PSA after radical prostatectomy have a 25% likelihood of harboring an occult local recurrence. However, radiation therapy produces a sustained suppression of PSA to undetectable levels for 2 years or more in only 10% of men. This suggests that radiation therapy is not effective in sterilizing occult local residual tumor in many men. 10. Valuable information concerning disease recurrence and progression can be obtained through early postoperative measurement of serum PSA. This article demonstrates the long-term value of serum PSA as a measure of progression after anatomic radical prostatectomy.

Follow-Up Studies↗
PubMed1992

Use of nuclear morphometry, gleason histologic scoring, clinical stage, and age to predict disease-free survival among patients with prostate cancer.

BACKGROUND: Currently, there are no accurate methods for predicting metastases or time to disease progression for patients with clinically localized prostate cancer after surgery. METHODS: In this report, histologic sections were studied from prostate cancer specimens from 100 men with clinically localized prostate cancer (clinical Stages A1 [9 cases], A2 [24 cases], B1 [27 cases], and B2 [40 cases]; pathologic Stages A1 [9 cases], A2 [22 cases], B [23 cases], C1 [8 cases], and D1 [38 cases]) to determine whether nuclear morphometry--when analyzed with clinical stage, pathologic parameters, and age in a multivariate fashion--would predict time to disease progression. RESULTS: These patients were treated with surgery alone for their clinically localized disease and were observed after surgery until disease progression or death. For each of the 100 specimens, 16 different mathematical descriptors described the shape of 150 nuclei. A series of 17 different statistical measurements were calculated to accurately describe the distribution, extremes, and variability within each descriptor. As univariate predictors, the variance of nuclear roundness, the mean of ellipticity, the Gleason score, age, and clinical stage were statistically significant predictors of disease progression when analyzed with Kaplan-Meier survival curves. A prognostic factor score calculated with multivariate analysis of clinical stage, Gleason score, age, and variance of nuclear roundness separated the patients into three statistically distinct groups and predicted time to progression by the Kaplan-Meier life table and Cox proportional hazards analysis. CONCLUSIONS: This prognostic factor score may aid in stratifying patients into high-risk and low-risk groups for testing adjuvant therapies for prostate cancer.

Adenocarcinoma↗
PubMed1992

The use of nuclear morphometry to predict response to therapy in Wilms' tumor.

Using nuclear morphometric analysis, a retrospective study was made of 27 patients with Wilms' tumor. The blinded group consisted of 17 patients with Stage I and II favorable-histology Wilms' tumors who did not respond to therapy and ten patients with Stage III and IV favorable-histology Wilms' tumors who did respond. In this complex group of patients, multivariate analysis (with several morphologic descriptors) was used to predict which patients responded to therapy. No single-shape descriptor predicted the response to therapy (P greater than 0.5). However, three shape descriptors: maximum ellipticity (ME), standard error of bending energy (SEBE), and the range of chain code-maximum peak (RCCM), with the multivariate formula of (1131 x SEBE) + (-7 x ME) + (50 x RCCM) + 7.18, separated the two groups (P less than 0.004). This result was statistically significant. Using this multivariate equation and a cutoff value of 0.6 units, this test yielded a sensitivity of 94% and a specificity of 70%. This result, in a complex group of patients, suggests that nuclear morphometry may be useful in the initial assessment of patients with Wilms' tumor and warrants further analysis.

Cell Nucleus↗
PubMed1992

Prediction of prognosis in untreated stage A2 prostatic carcinoma.

Carcinoma is found unexpectedly in approximately 10% or more of the 400,000 prostatectomies performed annually in the United States. Patients with Stage A2 carcinoma die of their disease in only 35% of the cases. To alter the course of disease in these patients, 65% of Stage A2 patients may be treated unnecessarily by radical prostatectomy, radiation therapy, or hormonal therapy. An accurate method to predict the outcome of patients with Stage A2 carcinoma is needed. Histologic sections from 18 patients with Stage A2 prostatic carcinoma followed without further treatment until progression, or followed without progression, were evaluated by several investigators who did not have knowledge of patient outcomes and who employed standard pathologic grading systems as well as morphometric, cytophotometric, flow cytometric, and immunohistochemical techniques. Outcome was predicted correctly by random sampled absolute (17 of 18 cases) and relative (16 of 18) nuclear roundness factor (NRF), tumor volume expressed as percent of specimen (13 of 16), primary (13 of 18), secondary (14 of 18), sum (15 of 18), and worse (14 of 18) Gleason grades and prostate-specific antigen immunohistochemical findings (13 of 18) that produced statistically significant separation of the two groups. Significant separation was not obtained with Mostofi's pattern, nuclear, sum, and worse grades, Johns Hopkins' grade, absolute tumor volume, nuclear DNA content measured by image cytophotometric study of Feulgen-stained histologic sections and flow cytometric study of propidium iodide-labeled suspensions of nuclei obtained from paraffin blocks, nonrandom sampled NRF of worse and most prevalent neoplastic areas, and prostatic acid phosphatase and peanut agglutinin immunohistochemical study. NRF measured by a random technique best predicted outcome in these patients with A2 prostatic carcinoma and should be evaluated prospectively as a means for selecting patients who require therapy.

Adenocarcinoma↗