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Biomedical subjects

Alan W Partin

Publications and source records attributed to Alan W Partin.

At least 19 recordsLinked to original sources
PubMed2007

Antibody array profiling reveals serum TSP-1 as a marker to distinguish benign from malignant prostatic disease.

BACKGROUND: Blood protein markers that provide more accurate or earlier diagnosis of prostate cancer should have a positive impact on prostate cancer treatment and management. METHODS: Serum samples from control subjects and patients with benign or malignant prostatic disease were analyzed on antibody arrays targeting multiple candidate prostate cancer markers and detected with two-color, rolling-circle amplification (TC-RCA). The measurements of certain antibodies were validated using immunoblots, immunoprecipitation/mass spectrometry, and sandwich immunoassays. RESULTS: Several potential disease-associated protein alterations were uncovered. The most significant was thrombospondin-1, which was strongly elevated in patients with benign prostatic disease and repressed in patients with prostate cancer. Thrombospondin-1 levels did not correlate with prostate-specific antigen (PSA) levels and differentiated benign from malignant disease with 79% sensitivity and 81% specificity. CONCLUSIONS: The measurement of thrombospondin-1 could be used to assist the decision to obtain a biopsy in men with suspected prostate cancer, which could lead to a reduction in the number of unnecessary prostatic biopsies.

Adult↗
PubMed2006

Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial.

CONTEXT: Prostate safety is a primary concern when aging men receive testosterone replacement therapy (TRT), but little information is available regarding the effects of TRT on prostate tissue in men. OBJECTIVE: To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial of 44 men, aged 44 to 78 years, with screening serum testosterone levels lower than 300 ng/dL (<10.4 nmol/L) and related symptoms, conducted at a US community-based research center between February 2003 and November 2004. INTERVENTION: Participants were randomly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months. MAIN OUTCOME MEASURES: The primary outcome measure was the 6-month change in prostate tissue androgen levels (testosterone and dihydrotestosterone). Secondary outcome measures included 6-month changes in prostate-related clinical features, histology, biomarkers, and epithelial cell gene expression. RESULTS: Of the 44 men randomized, 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per-protocol analysis (TRT, n = 21; placebo, n = 19). Testosterone replacement therapy increased serum testosterone levels to the mid-normal range (median at baseline, 282 ng/dL [9.8 nmol/L]; median at 6 months, 640 ng/dL [22.2 nmol/L]) with no significant change in serum testosterone levels in matched, placebo-treated men. However, median prostate tissue levels of testosterone (0.91 ng/g) and dihydrotestosterone (6.79 ng/g) did not change significantly in the TRT group. No treatment-related change was observed in prostate histology, tissue biomarkers (androgen receptor, Ki-67, CD34), gene expression (including AR, PSA, PAP2A, VEGF, NXK3, CLU [Clusterin]), or cancer incidence or severity. Treatment-related changes in prostate volume, serum prostate-specific antigen, voiding symptoms, and urinary flow were minor. CONCLUSIONS: These preliminary data suggest that in aging men with late-onset hypogonadism, 6 months of TRT normalizes serum androgen levels but appears to have little effect on prostate tissue androgen levels and cellular functions. Establishment of prostate safety for large populations of older men undergoing longer duration of TRT requires further study. Trial Registration clinicaltrials.gov Identifier: NCT00161304.

Adult↗
PubMed2006

Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10.

BACKGROUND: Men with a biopsy Gleason sum of 8 to 10 are considered high-risk. The current study sought to identify whether there was a subset of men with high biopsy Gleason sums who would have a good pathologic and biochemical outcome with surgical monotherapy. To increase the generalizability of the findings, data were used from patients treated at 2 very different practice settings: a tertiary care referral center (Johns Hopkins Hospital) and multiple equal-access medical centers (Shared Equal Access Regional Cancer Hospital [SEARCH] Database). METHODS: The data were retrospectively reviewed from men with biopsy Gleason sums 8 to 10 treated by radical prostatectomy at the Johns Hopkins Hospital (n = 220, 3.8% of total cohort) and within the SEARCH Database (n = 149, 7.7% of total cohort). The preoperative clinical characteristics predicting unfavorable pathologic disease (nonorgan-confined and/or positive surgical margins) and time to biochemical recurrence were determined using logistic regression and Cox proportional hazards analysis, respectively. RESULTS: Favorable pathologic outcome (organ-confined and negative surgical margins) was observed in 21% of the men in the Johns Hopkins cohort and 41% from the SEARCH cohort. On multivariate analysis, higher serum prostate-specific antigen (PSA) was the only variable that significantly predicted an unfavorable pathologic outcome from both the Johns Hopkins (P = .047) and SEARCH cohorts (P = .002). The 5-year and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 40% (95% confidence interval [CI], 33-48%) and 27% (95% CI, 18-36%), respectively, and 32% (95% CI, 22-42%) and 28% (95% CI, 18-38%) in the SEARCH cohort, respectively. Among men with favorable pathologic findings, the 5- and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 79% (95% CI, 62-89%) and 50% (95% CI, 25-71%), respectively, and 49% (95% CI, 32-65%) and 49% (95% CI, 32-65%) in the SEARCH cohort, respectively. No single preoperative variable significantly predicted the risk of biochemical progression in both the SEARCH or Johns Hopkins cohorts. CONCLUSIONS: The majority of men with a biopsy Gleason sum of >or=8, regardless of where the patient is treated, had unfavorable pathologic disease and experienced a biochemical progression after radical prostatectomy. Even among men with organ-confined disease and negative surgical margins or pathologic Gleason sum <8, at least half of the men experienced a PSA recurrence. Patients with biopsy Gleason sum 8 to 10 cancers are good candidates for multimodal therapy. Whereas multimodal therapy has often meant radiation plus hormonal therapy, newer possibilities for multimodal therapy exist such as surgery with neoadjuvant or adjuvant chemohormonal therapy or surgery with adjuvant radiation.

Aged↗
PubMed2006

Metabolic factors associated with benign prostatic hyperplasia.

CONTEXT: Benign prostatic hyperplasia poses a significant public health problem, but its etiology remains unclear. Obesity and associated abnormalities in glucose homeostasis may play a role in benign prostatic hyperplasia development by influencing prostate growth. OBJECTIVE: The objective of this study was to determine whether obesity, fasting plasma glucose concentration, and diabetes are associated with radiologically determined prostate enlargement, an objective measure of benign prostatic hyperplasia. DESIGN: This study was a cross-sectional analysis with robust variance estimates to account for multiple measures over time in the same individuals. SETTING: This prospective cohort study was composed of community volunteers. PATIENTS: Patients studied were 422 adult men enrolled in The Baltimore Longitudinal Study of Aging. MAIN OUTCOME MEASUREMENTS: Total prostate volume as determined by pelvic magnetic resonance imaging was measured. RESULTS: Among 422 participants, 91 (21.6%) had prostate enlargement (defined as total prostate volume >/= 40 cc) at first visit. Compared with men of normal weight [body mass index (BMI) < 25 kg/m(2)], the age-adjusted odds ratio (OR) for prostate enlargement for overweight men (BMI, 25-29.9 kg/m(2)) was 1.41 (95% CI, 0.84-2.37), for obese men (BMI, 30-34 kg/m(2)) was 1.27 (95% CI, 0.68-2.39), and for severely obese men (BMI >/= 35 kg/m(2)) was 3.52 (95% CI, 1.45-8.56) (P = 0.01). Men with elevated fasting glucose (>110 mg/dl) were more likely to have an enlarged prostate than men with normal fasting glucose (</=110 mg/dl) (OR, 2.98; 95% CI, 1.70-5.23), as were men with a diagnosis of diabetes (OR, 2.25; 95% CI, 1.23-4.11). CONCLUSIONS: Obesity, elevated fasting plasma glucose, and diabetes are risk factors for benign prostatic hyperplasia.

Adult↗
PubMed2006

Pathological outcomes and biochemical progression in men with T1c prostate cancer undergoing radical prostatectomy with prostate specific antigen 2.6 to 4.0 vs 4.1 to 6.0 ng/ml.

PURPOSE: Recent studies have suggested that the cut point for recommending prostate biopsy among men with a normal digital rectal examination should be greater than 2.5 ng/ml as opposed to the more traditional greater than 4.0 ng/ml. We compared outcomes between men with clinical stage T1c disease undergoing radical prostatectomy who had a low vs slightly increased prostate specific antigen. MATERIALS AND METHODS: The study population consisted of 2,896 men treated with radical prostatectomy between 1985 and 2004 at a tertiary care referral center with clinical stage T1c disease and a pre-biopsy prostate specific antigen between 2.6 and 6.0 ng/ml. Using multivariate analysis we evaluated the association between pre-biopsy prostate specific antigen 2.6 to 4.0 ng/ml (784) vs 4.1 to 6.0 ng/ml (2,112), and pathological outcomes and biochemical progression. RESULTS: After adjusting for multiple clinical and pathological characteristics, lower preoperative serum prostate specific antigen values were associated with decreased odds of Gleason score 7 or greater in the surgical specimen (p = 0.004), positive surgical margins (p = 0.02) and extraprostatic extension (p = 0.001). There was no significant association between these preoperative prostate specific antigen groups and odds of seminal vesicle invasion (p = 0.47) or lymph node metastasis (p = 0.90). Among the 1,534 men with followup information available there was a trend for increased risk of biochemical progression associated with a higher preoperative prostate specific antigen, although this trend did not reach statistical significance (relative risk 1.48, 95% CI 0.69-3.19, p = 0.31). CONCLUSIONS: In the current study of men with clinical stage T1c treated with radical prostatectomy a lower preoperative prostate specific antigen was associated with significantly more favorable pathological findings. Whether this degree of improved outcomes justifies the limitations associated with decreasing the prostate specific antigen cut point (eg increased biopsies performed and diagnosis of insignificant cancers) remains to be determined.

Disease Progression↗
PubMed2006

Black race does not independently predict adverse outcome following radical retropubic prostatectomy at a tertiary referral center.

PURPOSE: There is controversy in the literature as to whether black race is associated with poorer oncological outcomes among men undergoing radical prostatectomy for clinically localized prostate cancer. To address this issue we examined the outcomes of a cohort of black and white men treated by multiple surgeons at our institution. MATERIALS AND METHODS: The study population consisted of 4,962 white and 326 black men treated with anatomical radical retropubic prostatectomy between 1988 and 2004 by 10 different surgeons at the Johns Hopkins Hospital, a tertiary care referral center. We evaluated the association between race and adverse pathological features, and biochemical progression. RESULTS: Black men had significantly higher preoperative serum prostate specific antigen (mean 7.2 vs 6.0 ng/ml, p <0.001), body mass index (median 27.4 vs 26.3 kg/m, p <0.001) and incidence of higher grade disease (Gleason sum 4 + 3 or greater) on prostate biopsy (17% vs 14%, p = 0.011). After adjustment for multiple clinical variables there was no statistically significant association between race and the adverse pathological characteristics of high grade disease, positive surgical margins, extraprostatic extension or seminal vesicle invasion. Black race was associated with a significantly increased risk of biochemical progression on univariate analysis (HR 1.52, 95% CI 1.16-2.00, p = 0.002). However, after adjusting for clinical and pathological characteristics, black race was not an independent predictor of biochemical progression (HR 1.09, 95% CI 0.81-1.45, p = 0.578). CONCLUSIONS: Black men were more likely to be obese and present with adverse preoperative clinical features at a younger age, and have a higher rate of biochemical progression. However, on multivariate analysis black race was not an independent predictor of adverse pathological outcome or biochemical recurrence. Further efforts are needed to detect prostate cancer earlier among black men.

Adenocarcinoma↗
PubMed2006

Time to prostate specific antigen recurrence after radical prostatectomy and risk of prostate cancer specific mortality.

PURPOSE: In patients treated with radical prostatectomy who have biochemical recurrence we have previously reported that time from surgery to biochemical recurrence and postoperative prostate specific antigen doubling time are significantly related to the risk of prostate cancer death. We performed a more thorough examination of the association of time from surgery to biochemical recurrence and the risk of prostate cancer death. MATERIALS AND METHODS: We retrospectively studied the records of 379 patients treated with radical prostatectomy between 1982 and 2000 who had had biochemical recurrence. We examined the association of time from surgery to prostate specific antigen recurrence and prostate specific antigen doubling time, and the risk of prostate cancer death using the Spearman correlation and Cox proportional hazards regression, respectively. RESULTS: Longer time from surgery to prostate specific antigen recurrence was associated with a slower prostate specific antigen doubling time (Spearman r = 0.36, p < 0.001) and a decreased risk of prostate cancer death (RR 0.76, 95% CI 0.66 to 0.88, p < 0.001). The 15-year actuarial prostate cancer specific survival rate after biochemical recurrence in patients with recurrence at 3 years or less was 41% (95% CI 29 to 53) compared to 87% (95% CI 75 to 93) in patients with recurrence more than 3 years after radical prostatectomy. On multivariate analysis a shorter time from surgery to prostate specific antigen recurrence was associated with an increased risk of prostate cancer death (3 or less vs more than 3 years, RR 2.70, 95% CI 1.37 to 5.31, p = 0.004). CONCLUSIONS: Earlier prostate specific antigen recurrence is associated with an increased risk of prostate cancer death. These data suggest that perhaps time to prostate specific antigen recurrence may be a reasonable intermediate end point in patients treated with radical prostatectomy, although this must be validated in other studies.

Aged↗
PubMed2006

Relationship between primary Gleason pattern on needle biopsy and clinicopathologic outcomes among men with Gleason score 7 adenocarcinoma of the prostate.

OBJECTIVES: To examine the relationship among needle biopsy primary grade, prostatectomy grade, and postprostatectomy biochemical recurrence among men with Gleason score 7 disease. METHODS: We identified 320 men with Gleason score 7 tumors on prostate biopsy treated with radical prostatectomy between 1991 and 2001 by a single surgeon. None of these patients had received neoadjuvant or adjuvant hormonal therapy or radiotherapy. The chi-square test and Kaplan-Meier method were used to evaluate the correlation among biopsy Gleason score, prostatectomy Gleason score, and biochemical recurrence. RESULTS: A total of 252 (79%) and 68 (21%) men had primary Gleason pattern 3 and 4 identified on needle biopsy, respectively. Of the patients with Gleason pattern 3 + 4 tumors on biopsy, 24% were upgraded to primary pattern 4 or more on final pathologic analysis. Of the patients with Gleason pattern 4 + 3 tumors on biopsy, 47% were downgraded to primary pattern 3 or less on final pathologic analysis. The actuarial risk of biochemical prostate-specific antigen recurrence was significantly lower among patients with Gleason pattern 4 + 3 on biopsy, if the prostatectomy Gleason score was downgraded to 3 + 4 or less (P = 0.03). CONCLUSIONS: Approximately 47% of men with a diagnosis of Gleason pattern 4 + 3 on needle biopsy are downgraded at radical prostatectomy and will have biochemical prostate-specific antigen recurrence-free outcomes similar to patients originally diagnosed with Gleason pattern 3 + 4 adenocarcinoma. This group of patients may benefit from definitive treatment such as radical prostatectomy for management of their disease.

Adenocarcinoma↗
PubMed2006

Alterations in nuclear structure and expression of proPSA predict differences between native Japanese and Japanese-American prostate cancer.

OBJECTIVES: To differentiate the benign and/or malignant epithelial cells in prostate cancer (PCa) glands of native Japanese (NJ) and Japanese-American (JA) men using biomarkers. METHODS: Tissue microarrays from radical prostatectomy specimens of cancerous and adjacent benign areas from 25 NJ and 25 JA prostate glands were studied. Image analysis was used to quantify total prostate-specific antigen (PSA) and proPSA immunohistochemical staining, as well as the variance of several morphometric features from Feulgen-stained epithelial cell nuclei. Logistic regression analysis was applied to determine whether quantitative nuclear grade (QNG) calculations and PSA immunohistochemical staining could differentiate the two test groups. RESULTS: The QNG model differentiated changes in the benign epithelium of the two Japanese groups with an area under the receiver operating characteristic curve of 84% and accuracy of 82% (P = 0.0001). A second QNG model differentiated changes in the malignant epithelium of the two groups with an area under the receiver operating characteristic curve of 84% and accuracy of 76% (P = 0.0023). Logistic regression models combining proPSA immunohistochemical data and QNG from either benign or malignant tissue components yielded areas under the receiver operating characteristic curve of 96% and 91% (P <0.0001) for differentiation of the JA and NJ groups, respectively. CONCLUSIONS: Unique nuclear morphometric alterations demonstrated by QNG combined with proPSA immunohistologic localization independently predicted for significant differences between NJ and JA men with PCa. These preliminary observations indicate a basis for biologic and molecular alterations in the benign adjacent and malignant epithelium between these two groups.

Asian↗
PubMed2006

Concordance rates and modifiable risk factors for lower urinary tract symptoms in twins.

INTRODUCTION: Lower urinary tract symptoms, which are common in older men, are thought to be determined genetically and by modifiable environmental risk factors. We examined the contribution of these 2 etiologic components in a cohort of U.S. twins. METHODS: In 1998, a questionnaire that assessed lower urinary tract symptoms, weight, height, alcohol consumption, cigarette smoking, and physical activity was sent out to members of the National Academy of Science-National Research Council Twins Registry. We analyzed 1,723 complete twin pairs with information on lower urinary tract symptoms and zygosity and who did not have a previous diagnosis of prostate cancer. We calculated concordance rates of categories of the International Prostate Symptom Score in monozygotic (MZ) and dizygotic (DZ) twins. Generalized estimating equations were used to calculate the odds ratio of having high-moderate/severe lower urinary tract symptoms. RESULTS: Concordance rates were higher in MZ than in DZ twins with concordance rate ratios of 2.2 and 6.9 depending on the specificity of definition of symptoms. Genetic factors contributed 72% to the risk of high-moderate/severe lower urinary tract symptoms. Taking into account correlated individuals, we observed high odds of lower urinary tract symptoms in obese men compared with lean men (odds ratio = 1.91; 95% confidence interval = 1.16-3.15 comparing first versus fourth quartile). Cigarette smoking was not associated with lower urinary tract symptoms, but alcohol consumption was positively associated. Men who were more physically active tended to have lower odds of lower urinary tract symptoms compared with less active men (0.62; 0.36-1.08). CONCLUSION: The findings indicate a strong genetic component of lower urinary tract symptoms, but also support previous studies that modifiable environmental risk factors are associated with this condition.

Aged↗
PubMed2006

The importance of pelvic lymph node dissection in men with clinically localized prostate cancer.

Despite advances in noninvasive staging, pelvic lymph node dissection (PLND) remains the most accurate means of detecting lymph node metastases in men with clinically localized prostate cancer. Nomograms exist that can identify patients at low risk for lymphatic metastases according to preoperative information. In general, it seems reasonable to omit PLND in men with a biopsy Gleason sum of 6 or less and a prostate-specific antigen level of 10 ng/mL or less. Ultimately, however, this decision should be made according to physician and patient preference, considering the low contemporary morbidity associated with PLND. When PLND is performed, studies suggest that an extended dissection maximizes the detection rate of nodal involvement. Retrospective data indicate that an extended dissection might play a therapeutic role in a subset of patients with a limited lymph node burden. However, this might be an artifact of stage migration, and prospective studies are needed to evaluate this further.

Journal Article↗
PubMed2005

Promoter hypermethylation as an independent prognostic factor for relapse in patients with prostate cancer following radical prostatectomy.

PURPOSE: To analyze the prognostic significance of six epigenetic biomarkers (APC, Cyclin D2, GSTP1, TIG1, Rassf1A, and RARbeta2 promoter hypermethylation) in a homogeneous group of prostate cancer patients, following radical prostatectomy alone. PATIENTS AND METHODS: Biomarker analyses were done retrospectively on tumors from 74 prostate cancer patients all with a Gleason score of 3 + 4 = 7 and minimum follow-up period of 7 years. Using quantitative methylation-specific PCR, we analyzed six gene promoters in primary prostate tumor tissues. Time to any progression was the primary end point, and development of metastatic disease and/or death from prostate cancer was a secondary point. The association of clinicopathologic and biomolecular risk factors to recurrence was done using the log-rank test and Cox proportional hazards model for multivariate analysis. To identify independent prognostic factors, a stepwise selection method was used. RESULTS: At a median follow-up time of 9 years, 37 patients (50%) had evidence of recurrence: biochemical/prostate-specific antigen relapse, metastases, or death from prostate cancer. In the final multivariate analysis for time to progression (TTP), the significant factors were age > 60 [hazard ratio (HR), 0.4; 95% confidence interval (95% CI), 0.2-0.8; P = 0.01], hypermethylation of GSTP1 (HR, 0.23; 95% CI; 0.09-0.64; P = 0.004), and hypermethylation of APC (HR, 3.0; 95% CI, 1.42-6.32; P = 0.004). In another multivariate analysis, a profile of hypermethylation of APC and cyclin D2 hypermethylation was significant as well: if either any one was hypermethylated (HR, 1.84; 95% CI, 0.92-3.72; P = 0.09) or if both were hypermethylated (HR, 4.3; 95% CI, 1.52-12.33; P = 0.01). CONCLUSIONS: Methylation status of selected genes in the prostate cancer specimen may predict for time to recurrence in Gleason 3 + 4 = 7 patients undergoing prostatectomy. These results should be validated in a larger and unselected cohort.

Adenomatous Polyposis Coli Protein↗