Biomedical subjects

Gerald Andriole

Publications and source records attributed to Gerald Andriole.

10 recordsLinked to original sources

PubMed2006

A prospective study of dietary alpha-linolenic acid and the risk of prostate cancer (United States).

BACKGROUND: Alpha-linolenic acid (ALA) is the most common omega-3 fatty acid in the Western diet. The relation of dietary intake of ALA to prostate cancer risk remains unresolved. OBJECTIVE: We prospectively evaluated total ALA and ALA from specific food sources including animal, fish, and plant sources in relation to prostate cancer risk. DESIGN: A cohort of 29,592 male participants (age 55-74 years) in the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was followed for an average of 5.1 years. RESULTS: We ascertained 1,898 cases of total prostate cancer, of which 1,631 were organ-confined cases (stage T1b to T3a and N0M0) and 285 were advanced stage cases (stage>or=T3b, N1, or M1). We found no association between total ALA intake and overall prostate cancer (multivariate RR comparing extreme quintiles=0.94; 95% CI=0.81-1.09; P for trend=0.76). The corresponding RRs for organ-confined and advanced prostate cancer were 0.94 (95% CI=0.80-1.10; P for trend=0.80) and 0.83 (95% CI=0.58-1.19; P for trend=0.34), respectively. In addition, no relations were observed between ALA intake from any specific food source and the risks of total, organ-confined, or advanced prostate cancer. ALA intake also showed no association with low grade (Gleason sum<7; 1,221 cases) tumors (P for trend=0.23) or high grade (Gleason sum>or=7; n=677 cases) tumors (P for trend=0.26). CONCLUSIONS: In this prospective study of predominantly Caucasian men who were screened annually for newly incident prostate cancer, dietary intake of total ALA and ALA from specific food sources was not associated with risk of total prostate cancer or prostate tumors that were defined by stage and grade.

Aged↗

PubMed2006

Prostate specific antigen changes as related to the initial prostate specific antigen: data from the prostate, lung, colorectal and ovarian cancer screening trial.

PURPOSE: Annual screening with PSA, although of unproven benefit, is currently used for prostate cancer early detection. A large fraction of screened men have low (less than 2 ng/ml) initial PSA. The yield over time of positive PSA screens (ie more than 4 ng/ml) in these men has not been well characterized in large cohorts in the United States. MATERIALS AND METHODS: Men in the screening arm of the PLCO received baseline PSA and annual tests for 5 years. 30,495 of these men had baseline PSA 4 ng/ml or less. We estimated the cumulative probability of converting to PSA greater than 4 at years 1 through 5 as a function of baseline PSA. RESULTS: Among men with baseline PSA less than 1 ng/ml, 1.5% converted by year 5 (95% CI 1.2-1.7). Among men with baseline PSA of 1.0 to 1.99 ng/ml, 1.2% (95% CI 0.9-1.3) and 7.4% (95% CI 6.8-8.1) converted by year 1 and 5, respectively. A total of 33.5% and 79% of men with initial PSA of 2.0 to 2.99 and 3.0 to 4.0, respectively, converted by year 5. Of men with baseline PSA less than 1 ng/ml converting to PSA more than 4 ng/ml, 8% were diagnosed with cancer within 2 years of conversion. About 10% of men with baseline PSA less than 1 ng/ml and negative baseline DRE had a positive DRE within 3 years. CONCLUSIONS: For men choosing PSA screening, screening every 5 years for baseline PSA less than 1 ng/ml and every 2 years for PSA 1 to 2 ng/ml could result in a 50% reduction in PSA tests and in less than 1.5% of men missing earlier positive screens, but with an unknown effect on prostate cancer mortality.

Aged↗

PubMed2005

Genetic variation in the HSD17B1 gene and risk of prostate cancer.

Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17beta-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Delta5-androsterone-3beta,17beta-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G) or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002) inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes these subgroup analyses less reliable. These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites.

17-Hydroxysteroid Dehydrogenases↗

PubMed2005

The effects of 5alpha-reductase inhibitors on the natural history, detection and grading of prostate cancer: current state of knowledge.

PURPOSE: The Prostate Cancer Prevention Trial (PCPT) showed that the 5alpha-reductase inhibitor (5ARI) finasteride significantly decreased the 7-year period prevalence of prostate cancer vs placebo. However, Gleason score 7-10 tumors were significantly more common in the finasteride vs the placebo group. We considered data on the effects of 5ARIs on prostate cancer natural history and detection. MATERIALS AND METHODS: A detailed review was performed of the literature identified from the MEDLINE database examining the effects of 5ARIs on prostate cancer prevalence and tumor histopathology. RESULTS: In PCPT there were fewer biopsies performed for cause in the finasteride vs the placebo group and the proportion of high grade tumors in the treatment groups did not diverge with time. Given that finasteride has an effect on prostate specific antigen and prostate volume, which are key factors in triggering prostate biopsies, they may be significant confounders of Gleason score results. Prostate shrinkage in the finasteride treated group may minimize biopsy sampling error. Furthermore, histological studies have shown that 5ARIs have a significant effect on prostate architecture, which can make the interpretation of prostate specimens in men treated with 5ARIs difficult. Further evaluation of PCPT findings will help determine the true nature of these observations. CONCLUSIONS: 5ARIs decrease the risk of prostate cancer but also alter the detection of disease through effects on prostate specific antigen, and prostate volume and histology. The weight of evidence suggests an artifactual effect of finasteride on Gleason grading in the PCPT. The role of 5ARIs for prostate cancer chemoprevention needs further examination before it can be considered for wide recommendation.

Antineoplastic Agents↗

PubMed2004

Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial.

PURPOSE: Chemoprevention may significantly impact the natural history of prostate cancer. The most potent intraprostatic androgen, dihydrotestosterone, has a significant role in the pathophysiology of prostate cancer. It represents a biologically plausible target for chemoprevention through the inhibition of 5alpha-reductase isoenzymes. MATERIALS AND METHODS: The Reduction by Dutasteride of Prostate Cancer Events clinical trial is an international, multicenter, double-blind, placebo controlled chemoprevention study designed to determine if dutasteride 0.5 mg daily decreases the risk of biopsy detectable prostate cancer. A total of 8,000 men will be randomized to receive dutasteride or placebo for 4 years. Eligible men must be 50 to 75 years old, have a serum prostate specific antigen of 2.5 to 10 ng/ml (ages 50 to 60 years) or 3.0 to 10 ng/ml (older than 60 years). Men must have a negative 6 to 12 core biopsy within 6 months prior to enrollment. Repeat biopsies will be taken at 2 and 4 years. The rates of prostate cancer for each treatment group will be compared. Genetic and protein biomarkers of prostate cancer, and the effect of dutasteride on benign prostatic hyperplasia and prostatitis symptomatology and histopathology will also be assessed. RESULTS: Results remain to be determined. CONCLUSIONS: The study will examine the effects of the dual 5alpha-reductase inhibitor dutasteride on the natural history of prostate cancer in men at increased risk for this malignancy. It affords a unique opportunity to examine biomarkers and genetic linkage for prostate cancer, and assess a range of prostate health outcome measures.

5-alpha Reductase Inhibitors↗

PubMed2004

Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia.

PURPOSE: We reviewed the physiological and pathogenic role of dihydrotestosterone (DHT), evidence for the beneficial effects of decreasing DHT through 5alpha-reductase inhibition and the effects of altering the androgen balance with these agents. MATERIALS AND METHODS: A review of the relevant literature was done using published studies identified from the MEDLINE database. RESULTS: The androgens DHT and testosterone have complementary roles in male physiology. Each is mediated through the intracellular androgen receptor. It has been hypothesized that DHT may provide an amplification mechanism for testosterone, which could be a beneficial adaptation in men with low circulating testosterone. The recognition of the central role of DHT in benign prostatic hyperplasia (BPH) has changed the way the disease is viewed and has led to the introduction of 5alpha-reductase inhibitors, which can prevent and retard the progression of BPH by suppressing DHT synthesis. The 5alpha-reductase inhibitors decrease prostate volume. In doing so they improve symptoms and urinary flow, and decrease the risks of acute urinary retention and the need for BPH related surgery. The predominant drug related adverse events with 5alpha-reductase inhibitors are reproductive events, that is typically decreased libido, impotence and ejaculatory dysfunction. These events occur in a minority of men and tend to decrease with a longer treatment duration. CONCLUSIONS: DHT appears to have an obligatory role in the development of BPH. The role of 5alpha-reductase inhibitors in the treatment of BPH has been firmly established with an adverse events profile that is suitable for long-term use.

5-alpha Reductase Inhibitors↗

PubMed2003

Surgical treatment of renal neoplasia: evolving toward a laparoscopic standard of care.

OBJECTIVES: To determine the extent to which laparoscopy has replaced open surgery for renal malignancy. METHODS: The records of all 537 patients at Washington University who underwent surgery for localized renal malignancies from January 1997 to December 2001 were examined for clinical and pathologic information. RESULTS: The total procedures per year increased from 1997 to 2001, but the distribution of pathologic stages throughout the 5 years was similar. In 1997, laparoscopic approaches were used in 15% of cases; this increased to 65% by 2001. Nephron-sparing surgery (NSS) was used in 31% to 42% of patients yearly, but laparoscopic NSS increased in frequency. By 2001, only 3.3% of T1 tumors were removed by open radical nephrectomy compared with 55% treated by laparoscopic nephrectomy. The rest of the T1 tumors in 2001 were treated by open partial nephrectomy (20.2%) or laparoscopic NSS (21.3%). In 2001, 61% of T2 lesions were treated laparoscopically, an increase from 37% in 1997. Most open radical nephrectomies in 2001 were performed for T3 disease. The number of surgeons performing laparoscopic renal surgery has increased at our institution, from two in 1997, both endourologists, to eight in 2001, representing the entire urology faculty that treats renal cancer. CONCLUSIONS: Laparoscopic radical nephrectomy has replaced open radical nephrectomy for low-stage renal neoplasia. Although laparoscopic NSS is increasing in frequency, it has not yet replaced open partial nephrectomy. At our institution, the laparoscopic approach has become the standard of care when radical nephrectomy is needed for T1 or T2 renal cancer.

Carcinoma, Renal Cell↗

PubMed2003

Radiation therapy for increasing prostate-specific antigen levels after radical prostatectomy.

Herein we present data on outcomes in patients with increasing prostate-specific antigen (PSA) levels treated with irradiation to the pelvis and/or prostatic bed after radical prostatectomy. Between 1988 and 1998, 92 patients who presented with increasing PSA levels after radical prostatectomy were treated with irradiation, 29 to the pelvis and prostatic bed and 63 to the prostatic bed only. The mean follow-up was 4 years for the 3D-CRT group and 6.5 years for the standard radiation therapy group. Criterion for biochemical failure was an increase in post irradiation PSA level on > or = 1 consecutive measurement. Patients were classified into 3 risk groups based on prognostic factors: pathologic tumor extent and stage, Gleason score, and PSA levels before irradiation. Acute and late morbidity was quantitatively evaluated in all patients. There was a close correlation between the preirradiation PSA level and the probability of 4-year biochemical failure-free survival (75% with PSA levels < or = 1 ng/mL, 30% with PSA levels of 1.1-2 ng/mL, and 20% with PSA levels > 2 ng/mL; P = 0.05). The 4-year chemical failure rate was 20% in the low/intermediate-risk group and 65% in the high-risk group (P = 0.36). In 20 patients in the low-PSA group (< or =1 ng/mL) receiving doses > 62 Gy, no biochemical failures have been detected in comparison to a 70% failure rate at 4 years in patients treated with lower doses (P = 0.15). In the higher-PSA groups, no impact of irradiation dose on outcome was noted (40%-60% incidence of failure at 3 years). Pelvic irradiation was associated with a trend toward decreased biochemical failure rate in the low-PSA group (70% vs. 0% at 4 years; P = 0.35), but not in the high-PSA group. Only 1 patient (1.5%) experienced clinical local recurrence in the prostatic bed and 2 patients (1.8%) had distant metastases. Treatment has been very well tolerated, with only 3 patients in the arc-rotation group experiencing grade 2 treatment toxicity. Prostate bed irradiation is an effective treatment in a significant proportion of patients who present with a biochemical failure after radical prostatectomy.

Acute Disease↗

PubMed2002

Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia.

OBJECTIVES: To study the efficacy and safety of dutasteride, a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II. METHODS: A total of 4325 men (2951 completed) with clinical benign prostatic hyperplasia, moderate to severe symptoms (American Urological Association-Symptom Index score of 12 points or greater), a peak flow rate of 15 mL/s or less, a prostate volume of 30 cm3 or greater (as measured by transrectal ultrasonography), and a serum prostate-specific antigen level of 1.5 to 10.0 ng/mL (inclusive) were enrolled into three identical clinical trials and randomized to 0.5 mg dutasteride daily or placebo. After a 1-month, single-blind, placebo lead-in, patients were followed up for 24 months in a double-blind trial with multiple interval assessments. RESULTS: At 24 months, serum dihydrotestosterone was reduced from baseline by a mean of 90.2% (median -93.7%; P <0.001), and the total prostate and transition zone volumes were reduced by a mean of 25.7% and 20.4%, respectively (P <0.001). The symptom score was improved by as early as 3 months, with pooled significance from 6 months onward (P <0.001) and a reduction of 4.5 points (21.4%) at 24 months (P <0.001). The maximal flow rate improved significantly from 1 month (P <0.01), with an increase of 2.2 mL/s reported at 24 months (P <0.001). Hence, the risk reduction of acute urinary retention was 57% and the risk reduction of benign prostatic hyperplasia-related surgical intervention was 48% compared with placebo. The drug was well tolerated. CONCLUSIONS: Dutasteride is a potent inhibitor of dihydrotestosterone production that is safe and effective in terms of the reduction of prostate volume and symptoms, flow rate improvement, and the reduction of the risk of acute urinary retention and surgery during a 24-month study period.

5-alpha Reductase Inhibitors↗

PubMed2002

Office-based transurethral microwave thermotherapy using the TherMatrx TMx-2000.

BACKGROUND AND PURPOSE: Transurethral microwave thermotherapy (TUMT) is an effective therapy for symptomatic benign prostatic hyperplasia (BPH), but the trade-off between the magnitude of clinical improvement and side effects and patient tolerance has limited its appeal to patients and urologists. This study, using the TherMatrx TMx-2000, a TUMT device that directly heats the transition zone to greater than 50 degrees C, has been focused on resolving these issues and developing a truly office-based therapy that is well tolerated with a benign post-treatment course. PATIENTS AND METHODS: This study was multi-institutional and designed as a blinded, randomized, and sham-controlled trial. A series of 200 patients with an AUA Symptom Index (AUASI) of >12, a peak flow rate of <12 mL/sec, and cystoscopic evidence of BPH were randomized 2:1 (active to sham) and treated in seven physician offices under a Food and Drug Administration-supervised and audited premarket approval protocol. No intravenous sedation was used in any patient. Follow-up for the sham-treatment group was 3 months, at which time, patients could cross over to an active treatment. A total of 119 patients have completed 1-year follow-up. RESULTS: The active and sham groups were statistically identical at baseline. The 1-hour total treatment was extremely well tolerated using urethral lidocaine and oral medications; not a single prostate block or parental dose of medication was required. The active-treatment group demonstrated a statistically significant reduction (p < 0.05) in AUASI at 3 months compared with sham treatment, with an AUASI decrease from 22.4 to 12.4 (n = 124) for active v 22.9 to 17 for sham (n = 62). For the 119 patients in the active arm who have reached 12 months, the AUASI has fallen to 10.6 points (47.1% decrease), and the peak flow rate has increased 5.0 mL/sec (58.1%). Postprocedure catheterization was typically 2 or 3 days, and the 16.8% of patients who failed their first voiding trial all voided within 1 week. No major adverse events such as stricture, rectal findings, or ejaculatory changes have been reported. CONCLUSIONS: This study demonstrates that the TherMatrx TMx-2000 TUMT effectively treats symptomatic BPH in the physician office with minimal morbidity.

Aged↗