Surgical Specialist, Oncology Specialist (cancer), Urologists
33 years of experience

Accepting new patients
Durham Va Medical Center
508 Fulton St
Durham, NC 27705
919-286-0411
Locations and availability (4)

Education ?

Medical School
Tulane University (1977)

Awards & Distinctions ?

Awards  
One of America's Leading Experts on:
Prostate Cancer (Prostatic Neoplasm)
Castle Connolly America's Top Doctors® (2004 - 2008, 2010 - 2014)
Castle Connolly America's Top Doctors® for Cancer (2005 - 2007, 2009 - 2012, 2014)
Patients' Choice Award (2011)
Compassionate Doctor Recognition (2011)
Appointments
Duke University School of Medicine
Associate Professor of Surgery
Duke University Medical Center
Associations
American Urological Association
Member
Society of Urologic Oncology
Member
American Society of Clinical Oncology
Member
American College of Surgeons
Member
American Urological Association (urologyhealth.org)
Member

Affiliations ?

Dr. Robertson is affiliated with 7 hospitals.

Hospital Affilations

Score

Rankings

  • Duke Raleigh Hospital
    Medical Oncology
    3400 Wake Forest Rd, Raleigh, NC 27609
    • Currently 4 of 4 crosses
    Top 25%
  • Durham Regional Hospital
    Urology
    3643 N Roxboro St, Durham, NC 27704
    • Currently 3 of 4 crosses
    Top 50%
  • Duke University Hospital *
    Urology
    2301 Erwin Rd, Durham, NC 27710
    • Currently 3 of 4 crosses
    Top 50%
  • Durham VA Medical
  • Durham Veterans Affairs Medical Center
    508 Fulton St, Durham, NC 27705
  • Durham Regional Hospital Medical Staff Services
  • Veterans Affairs Med Ctr, Durham, Nc
  • * This information was reported to Vitals by the doctor or doctor's office.

    Publications & Research

    Dr. Robertson has contributed to 87 publications.
    Title Factors Predicting Early and Late Phase Decline of Sexual Health-related Quality of Life Following Radical Prostatectomy.
    Date February 2012
    Journal The Journal of Sexual Medicine
    Excerpt

    The association between early and late phase sexual health-related quality of life (HRQoL) following radical prostatectomy (RP) is unclear. Moreover, factors that predict either early or late sexual HRQoL decline have not been fully investigated.

    Title Kidney Cancer.
    Date January 2012
    Journal Journal of the National Comprehensive Cancer Network : Jnccn
    Title Predicting Occult Multifocality of Renal Cell Carcinoma.
    Date January 2011
    Journal European Urology
    Excerpt

    Multifocal renal cell carcinoma (RCC) has been reported in up to 25% of all radical nephrectomy specimens. Modern imaging tends to underestimate the rate of multifocality. Recognition of multifocality before treatment may guide physicians and patients to the type of intervention and tailor long-term follow-up.

    Title Adjuvant Versus Salvage Radiation Therapy for Prostate Cancer and the Risk of Death.
    Date January 2011
    Journal Bju International
    Excerpt

    To investigate whether salvage radiation therapy (RT) for prostate-specific antigen (PSA) failure can provide the same result as adjuvant RT, which decreases the risk of all-cause mortality (ACM) for men with positive margins (R1), or extra-capsular or seminal vesicle extension (pT3).

    Title Prostate-specific Antigen-based Risk-adapted Discontinuation of Prostate Cancer Screening in Elderly African American and Caucasian American Men.
    Date December 2010
    Journal Urology
    Excerpt

    To evaluate the relationship between initial prostate-specific antigen (PSA) and prostate cancer (PCa) risk in elderly African American (AA) and Caucasian American (CA) men.

    Title Predicting Non-organ-confined Prostate Cancer in Men Diagnosed After 2000.
    Date December 2010
    Journal Prostate Cancer and Prostatic Diseases
    Excerpt

    The objective of this study was to preoperatively predict non-organ-confined disease in patients considering radical prostatectomy. To account for the stage migration seen in prostate cancer, we included only those patients who underwent prostatectomy after the year 2000. Information on a cohort of 1895 patients who underwent radical prostatectomy from 2000 to 2008 was retrieved from the Duke Prostate Center database. Race (African American, non-African American), body mass index, age at surgery, PSA, biopsy Gleason sum (<7, 7 and >7) and clinical tumor stage (cT1, cT2/3) were analyzed by univariate analysis followed by logistic regression analysis. The Duke Interactive Clinical Equation for staging (DICE-S score) was calculated from the logistic regression model. The model was then internally validated using a bootstrapping technique. Biopsy Gleason sums 7 and >7 were more likely to have non-organ-confined disease compared with <7 (OR=2.97, Gleason sum=7; OR=3.25, Gleason sum>7). Clinical tumor stage, cT2/3, predicted non-organ-confined disease (OR=1.58). Older age was associated with non-organ-confined disease (OR=1.02), as was greater PSA (OR=1.12). DICE-S equation x=ln (p/1-p)=-3.627+0.019 (age)+0.109 (PSA)+1.087 (bGleason=7)+1.180 (bGleason >7)+0.459 (clinical T stage >T1), where p=(e(x))/(1+e(x)). A concordance index (prediction accuracy) of 0.73 was reached on internal validation. Using the DICE-S score, age, PSA, biopsy Gleason sum and clinical tumor stage, we can predict non-organ-confined disease in radical prostatectomy at an acceptable accuracy. Preoperative information on disease stage may aid in treatment decisions and surgical approach.

    Title Testicular Cancer. Clinical Practice Guidelines.
    Date August 2010
    Journal Journal of the National Comprehensive Cancer Network : Jnccn
    Title Kidney Cancer. Clinical Practice Guidelines.
    Date August 2010
    Journal Journal of the National Comprehensive Cancer Network : Jnccn
    Title Factors Predicting Prostatic Biopsy Gleason Sum Under Grading.
    Date June 2010
    Journal The Journal of Urology
    Excerpt

    We determined clinical factors affecting the under grading of biopsy Gleason sum compared with prostatectomy pathology and developed a model predicting the probability of under grading.

    Title Public Survey and Survival Data Do Not Support Recommendations to Discontinue Prostate-specific Antigen Screening in Men at Age 75.
    Date June 2010
    Journal Urology
    Excerpt

    To evaluate the US Preventative Services Task Force (USPSTF) recommendation to discontinue prostate-specific antigen (PSA) screening at age 75.

    Title Impact of Postoperative Prostate-specific Antigen Disease Recurrence and the Use of Salvage Therapy on the Risk of Death.
    Date May 2010
    Journal Cancer
    Excerpt

    This report evaluated whether biochemical recurrence (BCR) as a time-dependent covariate (t) after radical prostatectomy (RP) for prostate cancer was associated with the risk of death and whether salvage therapy with radiotherapy (RT) and/or hormonal therapy (HT) can lessen this risk

    Title Tumor Volume, Tumor Percentage Involvement, or Prostate Volume: Which is Predictive of Prostate-specific Antigen Recurrence?
    Date March 2010
    Journal Urology
    Excerpt

    To compare the effects of tumor volume (TV), tumor percentage involvement (TPI), and prostate volume (PV) on prostate-specific antigen (PSA) recurrence (PSAR) after radical prostatectomy (RP).

    Title Initial Prostate Specific Antigen 1.5 Ng/ml or Greater in Men 50 Years Old or Younger Predicts Higher Prostate Cancer Risk.
    Date March 2010
    Journal The Journal of Urology
    Excerpt

    Studies show that initial prostate specific antigen higher than the median in young men predicts a subsequent higher risk of prostate cancer. To our knowledge this relationship has not been studied in patients stratified by race.

    Title Tumor Percent Involvement Predicts Prostate Specific Antigen Recurrence After Radical Prostatectomy Only in Men with Smaller Prostate.
    Date March 2010
    Journal The Journal of Urology
    Excerpt

    We determined the predictive power of tumor percent involvement on prostate specific antigen recurrence in patients when stratified by prostate weight.

    Title A Retrospective Comparison of Anesthetic Management of Robot-assisted Laparoscopic Radical Prostatectomy Versus Radical Retropubic Prostatectomy.
    Date November 2009
    Journal Journal of Clinical Anesthesia
    Excerpt

    To compare anesthetic management and postoperative outcomes in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALP) and radical retropubic prostatectomy (RRP) with general anesthesia.

    Title Men Older Than 70 Years Have Higher Risk Prostate Cancer and Poorer Survival in the Early and Late Prostate Specific Antigen Eras.
    Date October 2009
    Journal The Journal of Urology
    Excerpt

    We clarified whether men older than 70 years have a higher risk of prostate cancer and poorer survival in the early and late prostate specific antigen eras.

    Title Delayed Prostate-specific Antigen Recurrence After Radical Prostatectomy: How to Identify and What Are Their Clinical Outcomes?
    Date September 2009
    Journal Urology
    Excerpt

    To identify factors that predict delayed (> 5 years) prostate-specific antigen recurrence (PSAR) after radical prostatectomy (RP) and to analyze the associated clinical outcomes.

    Title Effect of Age and Pathologic Gleason Score on Psa Recurrence: Analysis of 2911 Patients Undergoing Radical Prostatectomy.
    Date September 2009
    Journal Urology
    Excerpt

    To clarify the relationship between age and pathologic Gleason score and their effect on prostate-specific antigen recurrence (PSAR).

    Title Nccn Clinical Practice Guidelines in Oncology: Testicular Cancer.
    Date August 2009
    Journal Journal of the National Comprehensive Cancer Network : Jnccn
    Title Nccn Clinical Practice Guidelines in Oncology: Kidney Cancer.
    Date August 2009
    Journal Journal of the National Comprehensive Cancer Network : Jnccn
    Title Body Mass Index, Prostate-specific Antigen, and Digital Rectal Examination Findings Among Participants in a Prostate Cancer Screening Clinic.
    Date June 2008
    Journal Urology
    Excerpt

    OBJECTIVES: Prior studies suggested obese men have lower prostate-specific antigen (PSA) values. However, the association between body mass index (BMI) and digital rectal examination (DRE) findings and the association between weight at age 18 and adult PSA or DRE findings have not been examined. We sought to study the associations among BMI and weight at age 18 and adult PSA and DRE findings. METHODS: We analyzed data from 535 participants in a free prostate cancer-screening program in North Carolina held in September 2006. The associations among BMI and weight at age 18 and abnormal DRE and PSA levels were determined using multivariate logistic and linear regression models, respectively. RESULTS: A total of 391 men (73%) were overweight or obese, of whom 144 (27%) were obese. Mean +/- standard deviation and median age were 61.4 +/- 10.5 and 61 years, respectively; and 294 men (55%) were black, 219 (41%) white, and 22 (4%) neither black nor white. On multivariate analysis, higher BMI was significantly associated with lower PSA values (P = 0.03) but was not significantly associated with DRE findings. Weight at age 18 was not significantly related to adult PSA levels or DRE findings. CONCLUSIONS: In a multiethnic cohort of participants in a prostate cancer-screening clinic, obesity was associated with decreased PSA levels. We found no significant associations among BMI and DRE findings or weight at age 18 and adult PSA levels or DRE findings. The current data suggest that the PSA cut-points used to recommend biopsy need to be adjusted for the degree of obesity.

    Title Rectourethral Fistula After Combination Radiotherapy for Prostate Cancer.
    Date July 2007
    Journal Urology
    Excerpt

    OBJECTIVES: To describe 6 cases of rectourethral fistula in patients treated with brachytherapy plus external beam radiotherapy for localized prostate cancer and subsequent rectal biopsies or rectal surgery. METHODS: A retrospective chart review was undertaken of patients with prostate cancer treated with brachytherapy who presented to our institution with the diagnosis of rectourethral fistula from February 1999 to June 2002. Potential contributing factors, including patient age, cancer grade and stage, cancer treatment, rectal procedure, and time to the complication, were evaluated. Potential approaches to rectourethral fistula treatment and their outcomes are reported. RESULTS: The mean patient age was 63.8 years. All 6 men underwent combination prostate brachytherapy and external beam radiotherapy with subsequent rectal biopsy/hemorrhoidectomy. All 6 patients developed a rectourethral fistula, with an average time between the end of radiotherapy and fistula development of 22.6 months. Four patients underwent hyperbaric oxygen therapy, which failed. Three patients underwent fecal diversion with gracilis interposition flaps, and two underwent pelvic exenteration. CONCLUSIONS: The results of our study have shown that rectourethral fistula development is a serious complication of combination radiotherapy, with definitive repair requiring major intraabdominal surgery. Biopsy of rectal ulcers in the clinical setting of combined radiotherapy should not be performed. In addition, elective rectal surgery should not be performed on irradiated tissue. In our series, hyperbaric oxygen therapy and conservative treatment did not obviate the need for definitive surgical management of the rectourethral fistula.

    Title Testicular Cancer. Clinical Practice Guidelines in Oncology.
    Date May 2007
    Journal Journal of the National Comprehensive Cancer Network : Jnccn
    Title Kidney Cancer. Clinical Practice Guidelines in Oncology.
    Date May 2007
    Journal Journal of the National Comprehensive Cancer Network : Jnccn
    Title The Role of Early Adopter Bias for New Technologies in Robot Assisted Laparoscopic Prostatectomy.
    Date April 2007
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We determined the potential influence of an early adopter bias in patients undergoing robot assisted laparoscopic prostatectomy. MATERIALS AND METHODS: We compared baseline demographic, clinical and health related quality of life characteristics of patients undergoing 3 different surgical procedures for clinically localized prostate cancer following the introduction of robot assisted laparoscopic prostatectomy at our institution. Patients included in this analysis were participating in a prospective health related quality of life study using the SF-12(R) and Expanded Prostate Cancer Index Composite validated questionnaires. RESULTS: Of 402 patients 159 (39%) underwent robot assisted laparoscopic, 144 (36%) underwent radical perineal and 99 (25%) underwent radical retropubic prostatectomy. There were no statistically significant associations between procedure type and patient age (p = 0.267), race (p = 0.725), number of medical comorbidities (p = 0.490), income (p = 0.056) and level of education (p = 0.495). Mean prostate specific antigen was 5.9 +/- 3.3, 7.3 +/- 5.5 and 5.7 +/- 5.0 ng/ml for robot assisted laparoscopic, radical perineal and radical retropubic prostatectomy, respectively (p = 0.030). The proportion of robot assisted laparoscopic, radical perineal and radical retropubic prostatectomy patients with a final Gleason score of 4-6 was 55%, 45% and 39%, respectively (p = 0.037). The proportion of robot assisted laparoscopic, radical perineal and radical retropubic prostatectomy patients with stage T2 disease was 91%, 68% and 80%, respectively (p = 0.001). Statistically significant associations of higher income and education with higher baseline health related quality of life scores were seen in the sexual and physical domains (each p <0.01). CONCLUSIONS: We failed to find evidence of an early adopter bias for patients undergoing robot assisted laparoscopic prostatectomy. Nevertheless, observational studies comparing robot assisted laparoscopic prostatectomy to radical perineal and radical retropubic prostatectomy should account carefully for patient baseline characteristics to allow meaningful comparisons of surgical outcomes.

    Title Financial Comparative Analysis of Minimally Invasive Surgery to Open Surgery for Localized Prostate Cancer: a Single-institution Experience.
    Date March 2007
    Journal Urology
    Excerpt

    OBJECTIVES: To evaluate the financial implications of how the costs of new minimally invasive surgery such as laparoscopic robotic prostatectomy (LRP) and cryosurgical ablation of the prostate (CAP) technologies compare with those of conventional surgery. METHODS: From January 2002 to July 2005, 452 consecutive patients underwent surgical treatment for clinically localized (Stage T1-T2) prostate cancer. The distribution of patients among the surgical procedures was as follows: group 1, radical retropubic prostatectomy (RRP) (n = 197); group 2, radical perineal prostatectomy (RPP) (n = 60); group 3, LRP (n = 137); and group 4, CAP (n = 58). The total direct hospital costs and grand total hospital costs were analyzed for each type of surgery. RESULTS: The mean length of stay in the CAP group was significantly lower (0.16 +/- 0.14 days) than that for RRP (2.79 +/- 1.46 days), RPP (2.87 +/- 1.43 days), and LRP (2.15 +/- 1.48 days; P <0.0005). The direct surgical costs were less for the RRP (2471 dollars +/- 636 dollars) and RPP (2788 dollars +/- 762 dollars) groups than for the technology-dependent procedures: LRP (3441 dollars +/- 545 dollars) and CAP (5702 dollars +/- 1606 dollars; P <0.0005). The total hospital cost differences, including pathologic assessment costs, were less for LRP (10,047 dollars +/- 107 dollars, median 9343 dollars) and CAP (9195 dollars +/- 1511 dollars, median 8796 dollars) than for RRP (10,704 dollars +/- 3468 dollars, median 9724 dollars) or RPP (10,536 dollars +/- 3088 dollars, median 9251 dollars), with significant differences (P <0.05) between the minimally invasive technique and open surgery groups. CONCLUSIONS: In our study, despite the relatively increased surgical expense of CAP compared with conventional surgical prostatectomy (RRP or RPP) and LRP, the overall direct costs were offset by the significantly lower nonoperative hospital costs. The cost advantages associated with CAP included a shorter length of stay in the hospital and the absence of pathologic costs and the need for blood transfusion.

    Title Age Adjusted Prostate Specific Antigen and Prostate Specific Antigen Velocity Cut Points in Prostate Cancer Screening.
    Date February 2007
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We identified age adjusted prostate specific antigen and prostate specific antigen velocity cut points for prostate cancer biopsy. MATERIALS AND METHODS: A cohort of 33,643 men was retrieved from the Duke Prostate Center database. Of this group 11,861 men with 2 or more prostate specific antigen values within 2 years were analyzed for age adjusted prostate specific antigen and prostate specific antigen velocity performance in cancer risk assessment using a receiver operating characteristic curve. RESULTS: In the 11,861 men prostate cancer prevalence was 273 (8.0%), 659 (14.9%) and 722 (17.9%) in the groups of men 50 to 59 years old, 60 to 69 and 70 years old or older. In prostate cancer groups median prostate specific antigen and prostate specific antigen velocity in men 50 to 59 vs 70 years old or older were 5.6 vs 8.1 ng/ml and 1.37 vs 1.89 ng/ml per year (<0.0001). In men 50 to 59 years old the sensitivity and specificity were 82.1% and 80.7% at prostate specific antigen 2.5 ng/ml, and 84.3% and 72.4% at prostate specific antigen velocity 0.40 ng/ml per year, higher than those in men 70 years old or older at prostate specific antigen 4.0 ng/ml or prostate specific antigen velocity 0.75 ng/ml per year. Decreasing the prostate specific antigen cut point to 2.0 ng/ml and the prostate specific antigen velocity cut point to 0.40 ng/ml per year in men 50 to 59 years old improved the cancer detection rate but decreased the positive predictive value. CONCLUSIONS: Current biopsy guidelines (prostate specific antigen 4.0 ng/ml or greater, or prostate specific antigen velocity 0.75 ng/ml or greater per year) underestimated cancer risk in men 50 to 59 years old. Prostate specific antigen and prostate specific antigen velocity cut points should be age adjusted. In men 50 to 59 years old prostate specific antigen and prostate specific antigen velocity cut points could be decreased to 2.0 ng/ml and 0.40 ng/ml per year, respectively. Factors of age, sensitivity, specificity, positive predictive value and cancer prevalence are critical for obtaining the desired balance between cancer detection and negative biopsy.

    Title Timing and Patterns of Recurrences and Deaths from Prostate Cancer Following Adjuvant Pelvic Radiotherapy for Pathologic Stage T3/4 Adenocarcinoma of the Prostate.
    Date January 2007
    Journal Prostate Cancer and Prostatic Diseases
    Excerpt

    To determine the timing and patterns of late recurrence after radical prostatectomy (RP) alone or RP plus adjuvant radiotherapy (RT). Between 1970 and 1983, 159 patients underwent RP for newly diagnosed adenocarcinoma of the prostate and were found to have positive surgical margins, extracapsular extension and/or seminal vesicle invasion. Of these, 46 received adjuvant RT and 113 did not. The RT group generally received 45-50 Gy to the whole pelvis, then a boost to the prostate bed (total dose of 55-65 Gy). In the RP group, 62% received neoadjuvant/adjuvant androgen deprivation vs 17% in the RT group. Patients were analyzed with respect to timing and patterns of failure. Only one patient was lost to follow-up. The median follow-up for surviving patients was nearly 20 years. The median time to failure in the surgery group was 7.5 vs 14.7 years in the RT group (P=0.1). Late recurrences were less common in the surgery group than the RT group (9 and 1% at 10 and 15 years, respectively vs 17 and 9%). In contrast to recurrences, nearly half of deaths from prostate cancer occurred more than 10 years after treatment. Deaths from prostate cancer represented 55% of all deaths in these patients. Recurrences beyond 10 years after RP in this group of patients were relatively uncommon. Despite its long natural history, death from prostate cancer was the most common cause of mortality in this population with locally advanced tumors, reflecting the need for more effective therapy.

    Title Complications After Percutaneous Radiofrequency Ablation of Renal Tumors.
    Date January 2006
    Journal Urology
    Excerpt

    OBJECTIVES: To evaluate our experience with percutaneous radiofrequency ablation (pRFA) to determine common characteristics of patients with complications, to elucidate possible relative contraindications to therapy. METHODS: Medical records of all patients undergoing pRFA were reviewed for demographic data, medical and surgical history, indication, tumor characteristics, and treatment information (complications and management). The group of patients with complications was analyzed for common characteristics. RESULTS: From January 2000 to September 2003, 24 patients (mean age 61 years, 5:1 male/female) with 32 renal tumors were treated with pRFA. Indications for pRFA included prior renal surgery and/or chronic renal insufficiency, significant medical disease, patient choice, von Hippel-Lindau disease, and treatment of a metastasis. Average pretreatment tumor size was 2.4 cm (range 0.5-8.6 cm). Of the 5 patients experiencing complications from pRFA treatment, 2 developed perinephric hematomas, 1 had a persistent urinoma and proximal ureteral stricture, and 2 had colonic injuries. Among patients with complications, 3 of 5 had undergone prior partial nephrectomy on the pRFA-treated kidney. Two of four patients treated for multiple tumors and 57% of patients (4 of 7) with anteriorly located tumors experienced complications. CONCLUSIONS: Early experience with pRFA for renal tumor seems promising, but patient selection criteria are evolving. On the basis of our limited experience, we recommend caution when using renal pRFA in patients with prior partial nephrectomy, multiple tumors treated in the same setting, and tumors located anteriorly or centrally. Further clinical experience will help establish guidelines for the use of this powerful technology in the management of renal tumors.

    Title Supplement Use Among Men with Prostate Cancer.
    Date November 2005
    Journal Urology
    Excerpt

    OBJECTIVES: To characterize supplement use within a sample population of men diagnosed with prostate cancer. METHODS: A census of men diagnosed with prostate cancer at Duke University Medical Center from 1997 to 2002 (n = 1402) was mailed a survey that ascertained data on health status, education, diet, exercise, smoking status, and information on supplement use. Differences between demographic and treatment subgroups were described and tested, as was change in supplement use after diagnosis. RESULTS: Data from 805 respondents indicated that a majority (73%) used supplements, and 68% claimed that this information was shared with their cancer care provider. The most commonly reported supplements were multivitamins (56%), vitamin E (43%), vitamin C (33%), and calcium (26%). On average, 2.7 +/- 2.8 supplements per day were taken, and use increased significantly after diagnosis for most supplements. Use was significantly higher among men who were white (P = 0.043), were more highly educated (P = 0.002), exercise regularly (P = 0.020), and who consume five or more daily servings of fruits and vegetables (P = 0.040). CONCLUSIONS: A high percentage of men with prostate cancer take supplements, especially those who are white, more educated, and who pursue healthful behaviors. Systematic means of capturing these data are necessary to begin to understand the potential impact of supplements on disease outcome, especially because no data exist to suggest that supplements are of any benefit after diagnosis.

    Title Pilot Study to Explore Effects of Low-fat, Flaxseed-supplemented Diet on Proliferation of Benign Prostatic Epithelium and Prostate-specific Antigen.
    Date October 2004
    Journal Urology
    Excerpt

    OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.

    Title Comparison of [18 F]fluorocholine and [18 F]fluorodeoxyglucose for Positron Emission Tomography of Androgen Dependent and Androgen Independent Prostate Cancer.
    Date July 2002
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Positron emission tomography (PET) imaging is used for the metabolic evaluation of cancer. [18F]fluorodeoxyglucose (FDG) is commonly used as a radiotracer but its low cellular uptake rate in prostate cancer limits its usefulness. We evaluated the novel choline analog [18F]fluorocholine (FCH) for detecting androgen dependent and androgen independent prostate cancer, and its metastases. MATERIALS AND METHODS: The cellular uptake of FCH and FDG was compared in cultured prostate cancer cells (LNCaP and PC-3). FCH and FDG were injected into nude mice xenografts (CWR-22 and PC-3) and radiotracer uptake in various organs were evaluated. Patients with androgen dependent (9) and independent (9) prostate cancer were studied by FCH and FDG PET. RESULTS: FCH uptake was 849% and 60% greater than FDG uptake in androgen dependent (LNCaP) and independent (PC-3) cells, respectively. The addition of hemicholinium-3 (5 mM.) 30 minutes before radiotracer administration inhibited FCH uptake by 79% and 70% in LNCaP and PC-3 cells, respectively, whereas FDG uptake was not significantly affected. Although nude mice xenografts showed that FDG uptake was equal to or greater than FCH uptake, clinical imaging in patients demonstrated 2 to 4-fold higher uptake of FCH in those with androgen and androgen independent prostate carcinoma (p <0.001). More lesions were detected by FCH than by FDG in primary tumors, osseous metastases and soft tissue metastases. CONCLUSIONS: In vitro data demonstrated greater FCH than FDG uptake in androgen dependent (LNCaP) and androgen independent (PC-3) prostate cancer cells. Although the murine xenograft data showed greater accumulation of FDG than FCH in PC-3 tumors, PET in humans showed that FCH was better than FDG for detecting primary and metastatic prostate cancer. Overall the data from this study suggest that FCH is preferable to FDG for PET of prostate carcinoma and support the need for future validation studies in a larger number of subjects.

    Title Heat Shock Protein 70 (hsp70) Does Not Prevent the Inhibition of Cell Growth in Du-145 Cells Treated with Tgf-beta1.
    Date March 2002
    Journal Anticancer Research
    Excerpt

    BACKGROUND: Mitogen-activated protein kinase (MAPK) is one of the transforming growth factor-beta (TGF-beta signaling pathways while heat shock protein 70 (HSP70) prevents apoptosis by affecting MAPK signaling downstream. However, the interrelationship between TGF-beta and HSP70 signaling is still unknown. MATERIALS AND METHODS: DU-145 prostate cancer cells were treated with 40 pM and 200 pM TGF-beta1. After 3, 6, 9, 12 and 24 hours, cell proliferation assay and cell cycle analysis were performed. The activities of HSP70 and MAPKs (c-Jun N-terminal kinase 1 (JNK1), extracellular signal-regulated kinase 1 (ERK1), ERK2 and p38) were analyzed by Western blot at each time-point. RESULTS: TGF-beta1 inhibited the cell growth in a dose-dependent manner at 3 hours. Late G1 accumulation in the cell cycle was observed in a dose-dependent manner after 24 hours. HSP70 and JNK1 increased only at 3 hours and decreased for up to 24 hours thereafter. ERK1, ERK2 and p38 decreased from 3 to 24 hours after TGF-beta1 treatment. CONCLUSION: These data suggest that HSP70 does not prevent the inhibition of cell growth in DU-145 cells treated with TGF-beta1.

    Title Prostatic Sarcoma with Rapid Tumor Progression After Nerve Sparing Radical Cystoprostatectomy.
    Date October 2001
    Journal The Journal of Urology
    Title Pilot Study of Dietary Fat Restriction and Flaxseed Supplementation in Men with Prostate Cancer Before Surgery: Exploring the Effects on Hormonal Levels, Prostate-specific Antigen, and Histopathologic Features.
    Date August 2001
    Journal Urology
    Excerpt

    OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.

    Title Synthesis and Evaluation of 18f-labeled Choline As an Oncologic Tracer for Positron Emission Tomography: Initial Findings in Prostate Cancer.
    Date January 2001
    Journal Cancer Research
    Excerpt

    The up-regulation of rates of choline uptake and phosphorylation in certain malignancies has motivated the development of positron-labeled choline analogues for noninvasive detection of cancer using positron emission tomography (PET). The choline analogue, no-carrier-added [18F]fluoromethyl-dimethyl-2-hydroxyethyl-ammonium (FCH), was synthesized through the intermediate [18F]fluorobromomethane. FCH was evaluated in relationship to 2-[18F]fluoro-2-deoxyglucose (FDG) as an oncological probe in cultured PC-3 human prostate cancer cells, a murine PC-3 human prostate cancer xenograft model, and in PET imaging studies of patients with prostate cancer. FCH was synthesized in 20-40% radiochemical yield and >98% radiochemical purity. Accumulation of FCH and FDG were comparable in cultured prostate cancer cells, whereas only FCH was inhibited (90%) by hemicholinium-3, a specific inhibitor of choline transport and phosphorylation. FCH showed similar biodistribution to [14C]choline in the tumor-bearing mouse, with prominent renal and hepatic uptake. Tumor uptake of FCH was similar to choline and FDG in the mouse model, although tumor:blood ratios were moderately higher for FCH. Initial PET imaging studies in prostate cancer patients showed high uptake of FCH in advanced prostate carcinoma and detection of osseous and soft tissue metastases. FCH uptake by tumors was markedly reduced in patients rescanned during androgen deprivation therapy. It is concluded that FCH closely mimics choline uptake by normal tissues and prostate cancer neoplasms. FCH is potentially useful as a PET tracer for detection and localization of prostate cancer and monitoring effects of therapy.

    Title Early Onset Baldness and Prostate Cancer Risk.
    Date May 2000
    Journal Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
    Excerpt

    Prostatic carcinoma is the leading cancer among American men, yet few risk factors have been established. Although increased androgen levels have long been associated with both prostatic carcinoma and baldness, to date no studies have shown an association between hair patterning and prostate cancer risk. A lack of standardized instruments to assess baldness or the assessment of hair patterning during uninformative periods of time may have precluded the ability of previous studies to detect an association. We hypothesized that baldness, specifically vertex baldness, should be assessed using standardized instruments and during early adulthood if an association with prostate cancer risk is to be found. To test this hypothesis, we included identical items related to hair patterning in surveys that were administered in two distinct prostate cancer case-control studies (Duke-based study, n = 149; 78 cases; 71 controls and community-based study, n = 130; 56 cases; 74 controls). In each, participants were provided with an illustration of the Hamilton Scale of Baldness and asked to select the diagrams that best represented their hair patterning at age 30 and again at age 40. From these data, the following five categories were created and compared: not bald (referent group); vertex bald early onset (by age 30); vertex bald later onset (by age 40); frontal bald early onset (by age 30); frontal bald later onset (by age 40); and frontal (at age 30) to vertex bald (at age 40). Separate analyses of the two studies are consistent and suggest an association between vertex baldness and prostate cancer [vertex bald early onset odds ratios, 2.44 [confidence interval (CI), 0.57-10.46)] and 2.11 (CI, 0.66-6.73), respectively; vertex bald later onset odds ratios, 2.10 (CI, 0.63-7.00) and 1.37 (CI, 0.47-4.06), respectively]. Although statistical significance was not achieved in either one of these studies, the concordance between the data suggests a need for future studies to determine whether early onset vertex baldness serves as a novel biomarker for prostate cancer and whether androgen production, metabolism, or receptor status differs among these men when compared to those who exhibit other types of hair patterning.

    Title Transient Lumbosacral Polyradiculopathy After Prostatectomy: Association with Spinal Stenosis.
    Date September 1999
    Journal Southern Medical Journal
    Excerpt

    Mononeuropathies are common after pelvic surgery. They are usually the result of unnatural positioning during surgery or faulty restraining devices. Polyneuropathy in the postoperative setting is rare. We report two cases of polyradiculopathy after radical prostatectomy using two different patient positions. Both patients complained of paresthesias and weakness in their lower extremities on postoperative day 1. Neurologic examination in each case was consistent with a polyradiculopathy. Significant spinal stenosis of the lumbosacral spine was found in both patients by magnetic resonance imaging. We propose that spinal stenosis is a risk factor for this type of neurologic injury.

    Title Qol and Outcomes Research in Prostate Cancer Patients with Low Socioeconomic Status.
    Date August 1999
    Journal Oncology (williston Park, N.y.)
    Excerpt

    The VA Cancer of the Prostate Outcomes Study (VA CaPOS) is collecting quality-of-life (QOL) information from prostate cancer patients, spouses, and physicians at six VA medical centers. Currently, 601 men with prostate cancer are included in the study, most of whom are of low socioeconomic status and over half of whom are African-American. Quality-of-life responses were most favorable for newly diagnosed patients, intermediate for those with stable metastatic disease, and poorest for those with progressive metastatic disease. Patients could not provide reliable estimates of their own preferences for future QOL states but responded reliably to questions phrased as a comparison of the preferences of two hypothetical patients. High out-of-pocket costs for hormonal therapies, lack of health insurance, and a belief that the non-VA system offered poorer services were the most common reasons for patient transferral to the VA system. Satisfaction with medical care was generally high. While African-American patients were more likely to have advanced prostate cancer at diagnosis, after adjustment for differences in health literacy, race was no longer a significant predictor of advanced disease. The VA CaPOS provides useful information on health status and patient satisfaction of VA prostate cancer patients. Long-term evaluations are needed to detect clinically meaningful QOL information as the disease progresses.

    Title Molecular Cytogenetic Analysis of the Bladder Carcinoma Cell Line Bk-10 by Spectral Karyotyping.
    Date June 1999
    Journal Genes, Chromosomes & Cancer
    Excerpt

    The bladder cancer cell line BK-10 was established from a grade III-IV transitional cell carcinoma (TCC). BK-10 is near-tetraploid (+/-4n) and consists of two subclones with 20-25 structural aberrations. Here we report the cytogenetic analysis of BK-10 by G-banding, spectral karyotyping (SKY), and FISH. SKY refers to the hybridization of 24 differentially labeled chromosome painting probes and the simultaneous visualization of all human chromosomes using spectral imaging. SKY enabled us to confirm 12 markers in BK-10 previously described by G-banding, redefine 11 aberrations, and detect 4 hidden chromosomal rearrangements, 2 of which had been identified as normal or deleted copies of chromosome 20 and 1 as a normal chromosome 3. Twenty out of 21 translocations identified were unbalanced. FISH analysis of BK-10 using chromosome arm-specific paints, centromere probes, and oncogene/tumor suppressor gene-specific probes revealed a deletion of CDKN2A (p16) in all copies of chromosome 9, a low-level amplification of MYC (five copies), and loss of one copy of TP53; detected the presence of the Y chromosome in a hidden translocation; and detected four copies of ERBB-2. A probe set for BCR and ABL verified breakpoints for all translocations involving chromosomes 9 and 22. A new karyotype presentation, "SKY-gram," is introduced by combining data from G-banding, SKY, and FISH analysis. This study demonstrates the approach of combining molecular cytogenetic techniques to characterize fully the multiple complex chromosomal rearrangements found in the bladder cancer cell line BK-10, and to refine the chromosomal breakpoints for all translocations.

    Title Peptidyl Membrane-interactive Molecules Are Cytotoxic to Prostatic Cancer Cells in Vitro.
    Date March 1999
    Journal World Journal of Urology
    Excerpt

    Cytotoxic membrane disruption via lytic peptides is a well-recognized mechanism of immune surveillance for antifungal and antibacterial host protection. Naturally occurring lytic peptides were shown to exhibit antitumor activity as well. Peptidyl membrane-interactive molecules (MIMs) are synthetic lytic peptides specifically designed to maximize antitumor activity. We tested nine novel Peptidyl MIMs for activity against four androgen-insensitive prostate-cancer cell lines using a standard microculture tetrazolium (MTT) assay. Five Peptidyl MIMs known to form alpha-helical secondary structures were active against prostate carcinoma and were chosen for further study. Three peptides configured in beta-pleated sheets were noticeably less effective. Concentrations lethal to 50% of the prostate-cancer cell lines treated (D50 values) with the five chosen Peptidyl MIMs ranged from 0.6 to 1.8 microM. For comparison, two alpha-helically structured peptides, D2A21 and DP1E, were tested on several other cancer types: breast (n = 2), colon (n = 2). bladder, cervical and lung carcinomas (n = 1 each). Resulting LD50 values obtained in breast carcinoma cells were significantly higher (P < 0.05) than those observed in prostate cancer cells. LD50 values recorded for D2A21 and DP1E in cervical, colon, bladder, and lung cancer lines were similar to those obtained in prostate cancer cells. As compared with cisplatin, a standard chemotherapeutic drug, the LD50 values recorded for D2A21 were significantly lower (P < 0.04) in prostate-cancer cell lines, suggesting the therapeutic efficacy of Peptidyl MIMs. These data demonstrate for the first time the cytotoxic potential of Peptidyl MIMs against prostate cancer cells and suggest a dependence on a specific secondary alpha-helical structure of the peptide.

    Title Isolation and Characterization of a Novel Human Bladder Cancer Cell Line: Bk10.
    Date November 1998
    Journal In Vitro Cellular & Developmental Biology. Animal
    Excerpt

    Molecular studies of bladder carcinomas have aided in determining causative genetic events and the prognosis of cancers endowed with certain abnormalities. In vitro bladder cancer characterization of key cytogenetic alterations is useful for study of molecular changes that may promote oncogenic events. In our laboratory, a novel human bladder cancer cell line, BK10, has been established in vitro and passaged for more than 20 mo. This new bladder cancer cell line (BK10) was derived from bladder tissue containing grade III-IV/IV transitional cell carcinoma. Bladder cancer tissue was obtained at the time of radical cystoprostatectomy extirpation. Cell cultures derived from this surgical sample exhibited an epithelial morphology and expressed epithelial cytokeratins. Immunostains of BK10 were negative for prostate specific antigen (PSA), fibronectin, smooth muscle actin alpha, and desmin. Karyotypic analysis revealed an aneuploid chromosomal content <4n> with many numerical and structural abnormalities previously linked to bladder oncogenesis. Translocations occurred in chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, 15, 16, 17, 19, 20, 21, 22, X and Y. G-banding analysis revealed rearrangements involving chromosomes 9q and 17p, and the location of the ab11 oncogene and the p53 gene, respectively. The availability of this bladder cancer cell line will provide a useful tool for the further study of bladder carcinoma oncogenesis and gene therapy.

    Title Does Prostate Transitional Cell Carcinoma Preclude Orthotopic Bladder Reconstruction After Radical Cystoprostatectomy for Bladder Cancer?
    Date December 1997
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We determined if urethral preservation and orthotopic bladder replacement in patients with transitional cell carcinoma within the prostatic urethra or prostate placed these patients at risk for urethral recurrence or death. MATERIALS AND METHODS: The clinical course of all patients undergoing urethral preservation and orthotopic bladder replacement was reviewed. The urethra was sacrificed only if the distal prostatic urethral margin was positive for transitional cell carcinoma. The pathological T stage and the grade of the primary malignancy, local recurrence, site of recurrence (urethral, pelvic, distant) and death were documented. RESULTS: Of 81 patients 70 were evaluable (June 1996) with a mean followup of 35 months. Of the 70 patients 48 were alive without evidence of disease for a mean of 38 months (range 8 to 107) and 5 died without evidence of disease. Eight of these 53 patients (15%) had prostatic involvement (carcinoma in situ in 6, intraductal carcinoma in 1 and stromal invasive transitional cell carcinoma in 1). Of the 70 patients 17 had disease recurrence (13 died of disease and 4 are alive, 1 of whom had urethral recurrence without initial prostatic transitional cell carcinoma). Of the 17 patients (35%) 6 had transitional cell carcinoma prostatic involvement (carcinoma in situ in 4 and stromal invasion in 2), and 5 of these 6 died, none with or of urethral recurrence but of the primary bladder pathology. Of these 5 patients 1 had stromal invasive transitional cell carcinoma of the prostate and experienced a bulbar urethra recurrence at 1 month and a pelvic recurrence at 3 months, and died at 5 months. Death was not secondary to the urethral recurrence. Thus, of the 14 patients who had prostatic transitional cell carcinoma, only 1 had urethral recurrence (7%), and this recurrence did not present as the cause of death. CONCLUSIONS: The guidelines for urethral resection can be relaxed, increasing the opportunities for orthotopic reconstruction, without placing the patients at increased risk for death of transitional cell carcinoma.

    Title Serum Androgens: Associations with Prostate Cancer Risk and Hair Patterning.
    Date December 1997
    Journal Journal of Andrology
    Excerpt

    Cancer of the prostate is the leading cancer among American men, yet few risk factors have been established. Hair growth and development are influenced by androgens, and it has long been suspected that prostate cancer also is responsive to these hormones. A blinded, case-control study was undertaken to determine if hair patterning is associated with risk of prostate cancer, as well as specific hormonal profiles. The study accrued 315 male subjects who were stratified with regard to age, race, and case-control status (159 prostate cancer cases/156 controls). Hair-patterning classification and serum levels of total and free testosterone (T), sex hormone binding globulin, and dihydrotestosterone (DHT) were performed. Data indicate that hair patterning did not differ between prostate cancer cases and controls; however, significant hormonal differences were detected between the two groups. Free T was greater among cases than in controls (16.4 +/- 6.1 vs. 14.9 +/- 4.8 pg/ml, P = 0.02). Conversely, DHT-related ratios were greater among controls (P = 0.03 for DHT/T and P = 0.01 for DHT/free T). Several strong associations also were found between hormone levels and hair patterning. Men with vertex and frontal baldness had higher levels of free T (16.5 +/- 5.5 and 16.2 +/- 8.0 pg/ml, respectively) when compared to men with either little or no hair loss (14.8 +/- 4.7 pg/ml) (P = 0.01). Data suggest that increased levels of free T may be a risk factor for prostatic carcinoma. In addition, although no differences in hair patterning were detected between cases and controls within this older population, further research (i.e., prospective trials or case-control studies among younger men) may be necessary to determine if hair patterning serves as a viable biomarker for this disease, especially given the strong association between free T levels and baldness.

    Title Anthropometric Risk Factors for Prostate Cancer.
    Date November 1997
    Journal Nutrition and Cancer
    Excerpt

    Cancer of the prostate is the leading cancer among American men, yet few risk factors are known. Anthropometry may help uncover potential risk factors for prostate cancer, since fat distribution, skeletal structure, and musculature may differ between men with this hormonally linked cancer and those without it. A case-control study was undertaken to determine whether anthropometric differences exist between prostate cancer cases and controls and whether such differences are associated with specific hormonal profiles. The study accrued 315 men stratified for race, age, and case/control status. Weight, height (sitting/standing), skinfold thicknesses (triceps, biceps, subscapular, suprailiac, thigh), circumferences (midarm, waist, hip, thigh), breadths (elbow, biacromial, biiliac), hormonal levels (total and free testosterone, dihydrotestosterone, sex hormone-binding globulin), bone density, and body composition were measured. Measures of upper body robustness [i.e., biacromial breadth-to-height ratio (p = 0.02) and biacromial (p = 0.05) and bideltoid (p = 0.04) breadths] were greater among controls. Strong negative associations were found uniformly between sex hormone-binding globulin levels and measures of body adiposity and musculature. Data show that prostate cancer cases exhibit a propensity toward a slight upper body skeleton, which may in itself serve as a risk factor or provide a benchmark of past nutritional and/or hormonal status and help elucidate the etiology of this disease.

    Title Fenretinide: Induction of Apoptosis and Endogenous Transforming Growth Factor Beta in Pc-3 Prostate Cancer Cells.
    Date May 1997
    Journal Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
    Excerpt

    N-(4-Hydroxyphenyl)retinamide (4-HPR, Fenretinide) is a retinoid derivative with antineoplastic activity in various tumor types including prostate carcinoma. The mechanism of action of 4-HPR toxicity is unknown. 4-HPR induces apoptosis in leukemia- and lymphoma-derived cells, neuroblastoma, and small cell lung cancers. The present study was designed to investigate: (a) the mechanism of 4-HPR cytotoxicity in prostate cancer cells; and (b) correlate increased expression of transforming growth factor beta 1 (TGF beta 1) with induction of apoptosis. 4-HPR exposure to PC-3 cells in vitro was associated with apoptosis as evidenced by increased incidence of hypodiploid nuclei in propidium iodide fluorescence histograms and DNA fragmentation. An increase in the percentage of nuclei in the G1 phase of the cell cycle preceded induction of apoptosis. TGF beta 1-increased expression was noted in mRNA levels and in secretion of active TGF beta 1 into culture media. TGF beta 1 and TGF-beta receptor type II detected immunohistochemically were increased in 4-HPR-treated PC-3 cells. Furthermore, 4-HPR-induced cytotoxicity in PC-3 cells was abrogated by the addition of anti-TGF beta 1 antibody. In BT-20 cells, a 4-HPR-resistant breast carcinoma cell line, apoptosis was not observed after exposure to 4-HPR nor was TGF beta 1 expression enhanced in stained cells or in conditioned media. It is concluded that 4-HPR induces the expression of TGF beta 1 in association with the induction of apoptosis.

    Title Endoscopic Brush Cytology of the Upper Urinary Tract. Evaluation of Its Efficacy and Potential Limitations in Diagnosis.
    Date May 1997
    Journal Acta Cytologica
    Excerpt

    OBJECTIVE: To evaluate the efficacy of endoscopic brush cytology in diagnosing transitional cell carcinoma of the upper urinary tract. STUDY DESIGN: Sixty-three endoscopic brush cytology specimens from 48 patients were compared with corresponding cytologic specimens obtained by irrigation and catheterization as well as histologic specimens. RESULTS: Twenty patients (25 brushes) had histologically documented transitional cell carcinoma (TCC) or carcinoma in situ (CIS) of either the ureter or renal pelvis. Among these, 8 (32%) of the brush samples were reported as positive for TCC, 10 (40%) atypical or suspicious, and 7 (28%) negative. The seven negative cases were ultimately shown to be low grade (I-II/IV) TCC. Combining atypical and positive diagnoses, the calculated sensitivity for diagnosis of TCC by this technique was 72%. The irrigations or catheterized urines from these same patients yielded lower sensitivity, 48%, and detected only higher grade lesions. Ten patients were proven histologically to have nonneoplastic disease (hydroureter, obstruction, inflammation). Sixteen of the 17 brush specimens from these patients were negative, resulting in a specificity of 94%. In the remaining 18 patients (21 brushes) there were 17 negatives and 4 atypicals. Concomitant cytology supported the brush diagnosis in all but one sample. CONCLUSION: Brush cytology is a specific and more sensitive sampling method than irrigation or catheterized urine in detecting TCC of the upper urinary tract. Brush cytology does not appear to be successful in diagnosing dysplasia or CIS. As with urinary cytology in general, the technique is less effective in diagnosing low grade (I and II) lesions.

    Title Isolation and Characterization of a Novel Human Prostatic Stromal Cell Culture: Duk50.
    Date December 1996
    Journal In Vitro Cellular & Developmental Biology. Animal
    Excerpt

    A novel human prostatic stromal cell culture, designated DuK50, has been passed in vitro > 12 mo. Tissue cultures were obtained from material harvested within a normal region of a radical prostatectomy specimen. These monolayers exhibited normal fibroblastic characteristics with each cell having a flattened, elongated appearance. Karyotypic analysis revealed a normal, male 46, XY chromosomal content with no numerical or structural abnormalities. DNA analysis using a Cell Analysis Systems Image Analyzer confirmed a euploid DNA content (7.9 pg DNA). Cellular markers for verification of stromal cell type were performed by immunohistochemical techniques. DuK50 stained positive for vimentin and fibronectin. Immunostains for epithelial cytokeratins and prostate-specific antigen were negative, which ruled out contamination with prostatic epithelial cells. Negative immunostaining with desmin monoclonal antibody and light staining with smooth muscle actin alpha is consistent with the staining pattern of myofibroblasts. Response to various androgens, measured by a microculture tetrazolium assay technique, revealed a significant growth stimulation of DuK50. Soft agar invasiveness assays and tumorigenicity studies in nude mice were negative. DuK50 exhibits a rapid doubling time with excellent plating efficiency, thrives in a readily available media supplemented with fetal bovine serum, and passes with routine trypsin protocols. The availability of this prostatic stromal cell culture may facilitate studies on this cell type's role in growth factor modulation, drug and steroid metabolism, and stromal-epithelial interactions in the prostate.

    Title Correlation of Dna Ploidy and Histologic Diagnosis from Prostate Core-needle Biopsies: is Dna Ploidy More Sensitive Than Histology for the Diagnosis of Carcinoma in Small Specimens?
    Date November 1996
    Journal Journal of Surgical Oncology
    Excerpt

    DNA ploidy has been shown to have prognostic value in adenocarcinoma of the prostate. While occasional benign lesions of the prostate may be associated with a DNA aneuploid status, most aneuploid epithelial proliferations of the prostate are carcinomas. Because of the relationship between aneuploidy and malignancy, DNA ploidy analysis might improve detection of adenocarcinoma in small core-needle biopsy specimens. In this study, DNA ploidy analysis was performed on 186 fresh core biopsies from 32 patients who had undergone transrectal, ultrasonographically directed core-needle biopsies. Ploidy level was determined by Feulgen staining and image analysis with a CAS 200 image analyzer (Becton Dickinson-Cellular Imaging Systems, San Jose, CA). The resultant DNA ploidy levels were compared with the initial histologic diagnosis and subsequent clinical and pathologic follow-up. Nondiploid DNA patterns correlated with a diagnosis of carcinoma on core biopsy in 11 of 16 nondiploid cases and with a final diagnosis of malignancy in 13 of 16 nondiploid cases. Two patients with biopsy proven carcinoma had DNA diploid tumor patterns. Ploidy analysis had a sensitivity of 86.6% and a specificity of 73.7% in predicting the final diagnosis of malignancy. One case interpreted as DNA tetraploid by image analysis revealed seminal vesicle tissue on both the cytologic preparations and the core biopsy. Two DNA aneuploid specimen associated with cores initially read as benign or atypical demonstrated adenocarcinoma either on review of the original core biopsy or the prostatectomy specimen. The final DNA aneuploid specimen revealed acute prostatitis in the core biopsy. DNA ploidy analysis of core biopsy specimens appears to have relatively good specificity and sensitivity for the detection of prostatic carcinoma. Sampling errors appear to be the major cause of false negative results. Inappropriate measurement of seminal vesicle tissue and acute prostatitis can result in false positive results.

    Title Induction of Apoptosis by Diethylstilbestrol in Hormone-insensitive Prostate Cancer Cells.
    Date July 1996
    Journal Journal of the National Cancer Institute
    Excerpt

    BACKGROUND: Diethylstillbestrol (DES) and diethylstilbestrol diphosphate (DESdP) are effective agents for the treatment of advanced prostate cancers. Tumor-inhibiting effects of DES and DESdP are presumed secondary to suppression of androgen production in vivo. Little is known, however, about the direct cellular mechanisms of the tumor inhibition. Estrogens have been reported not only to stimulate growth but also to disrupt microtubule formation in prostate cancer cells. PURPOSE: The study was designed to examine and compare mechanisms of in vitro growth inhibition of DES and DESdP in human androgen-insensitive prostate cancer cells (DU145, 1-LN, and PC-3) and human androgen-sensitive prostate cancer cells (LNCaP) and to examine estrogen receptor modulation of such effects. METHODS: The cytotoxic effects of DES and DESdP were examined in vitro by use of a standard microculture tetrazolium assay to quantitate numbers of viable cells. Immunofluorescence microscopy, DNA fragmentation analysis, and fluorescence flow cytometry were used to investigate microtubules, the induction of apoptosis, and changes in cell cycle distribution. The degree of estrogen receptor positivity of untreated and treated cells was determined by immunohistochemistry and quantitative image analysis. RESULTS: LD50 levels (the dose at which 50% of cells are no longer viable) in the concentration range of 19-25 microM were observed for both DES and DESdP in all cell lines examined. DESdP-induced growth inhibition was found to be dependent on heat-labile phosphatases present in fetal calf serum. DES-induced cytotoxicity was not affected by the presence of 17 beta-estradiol, and it was not dependent on the presence of estrogen receptor. Estrogen receptor-positive cells and estrogen receptor-negative cells were equally responsive to DES. PC-3 cells stained with fluorescent anti-tubulin, phalloidin (actin stain), and 4',6-diamidino-2-phenylindole (DNA stain) showed no inhibition of microtubules or actin filaments but revealed the presence of apoptotic bodies in the nuclei. Fluorescence flow cytometry of nuclear DNA content of propidium iodide-stained nuclei from androgen-insensitive prostate cancer cells treated with 15 or 30 microM DES or DESdP revealed an increase in relative numbers of hypodiploid (apoptotic) nuclei, a depletion of G1- and S-phase cells, and an accumulation of cells in G2/M phase. Conversely, androgen-sensitive cells contained a lower percentage of hypodiploid nuclei but no accumulation of cells in G2/M phase. CONCLUSIONS: Direct cytotoxic effects of DES in prostate cancer cells are estrogen receptor independent and do not involve disruption of microtubule architecture but do involve the promotion of cell cycle arrest and apoptosis. These are the first data confirming direct cytotoxic effects of DES and DESdP in prostate cancer cells via an apoptotic mechanism. IMPLICATIONS. These results suggest that DES and DESdP have potential value as agents against androgen-insensitive prostate neoplasms through induction of an apoptotic cascade.

    Title The Alpha 1c-adrenoceptor in Human Prostate: Cloning, Functional Expression, and Localization to Specific Prostatic Cell Types.
    Date March 1996
    Journal British Journal of Pharmacology
    Excerpt

    1. Benign prostatic hyperplasia (BPH) causes urinary obstruction in aging men that frequently requires surgery to relieve the symptoms of urinary retention, nocturia, and micturition. Smooth muscle tone which contributes to the urethral constriction in the enlarged gland appears to be mediated by the alpha 1-adrenoceptors. In this paper, molecular and pharmacological approaches are used to establish the role played by the alpha 1C-adrenoceptor subtype in the prostate. 2. The alpha 1-adrenoceptor subtype(s) expressed in human prostate were investigated by use of polymerase chain reaction (PCR), Northern blot, and in situ hybridization. The alpha 1C subtype was found in both prostate stromal and glandular cells while alpha 1B and alpha 1D subtypes were expressed in glandular cells. High expression levels for alpha 1C were observed in prostate cancer tissues in both stroma and glandular cells. 3. Full length alpha 1C-adrenoceptor cDNA was cloned from human prostate. Stable mammalian cell lines expressing human alpha 1B-, alpha 1C-, and alpha 1D-adrenoceptors were made. Membranes prepared from these cell lines and human prostate were used to evaluate the pharmacological profiles of human alpha 1B-, alpha 1C- and alpha 1D-adrenoceptors in comparison to human prostate. Leverage plot analysis of compound affinities determined by competition for [125I]-I-HEAT binding demonstrated that the alpha 1C subtype is the predominant alpha 1-adrenoceptor in human prostate. 4. The alpha 1-adrenoceptors cause smooth muscle constriction by coupling to IP3 turnover and intracellular Ca2+ release. Using stable cell lines to measure IP3 production in response to noradrenaline, alpha 1C stimulated IP3 production most efficiently, with alpha 1B at an intermediate level, while little IP3 above background could be detected with alpha 1D. These results supported a functional role of the alpha 1C-adrenoceptor on prostate smooth muscle constriction by noradrenaline stimulation.

    Title Glutathione and Glutathione S-transferase in Benign and Malignant Prostate Cell Lines and Prostate Tissues.
    Date January 1996
    Journal Biochemical Pharmacology
    Excerpt

    Metastatic prostate adenocarcinoma is unresponsive to alkylator chemotherapy with virtually no prolonged remissions. Glutathione (GSH) and glutathione S-transferase (GST) have been reported to play a role in tumor resistance to alkylator therapy; however, there are no baseline studies that have investigated and compared GSH and GST in human prostate cell lines and tissues. Thus, we determined the GSH content and GST activity in benign prostate, in primary and metastatic prostate adenocarcinoma tissues, in immortal adenocarcinoma cell lines, and in primary cell cultures derived from both benign prostate and primary prostatic carcinoma tissue. The GSH content was higher in the immortal cell lines than in the fresh tissues and primary cultures. Conversely, the GST activity was significantly higher in the tissues and primary cultures than in the cell lines. The GSH content and GST activity of the primary cultured prostatic cells were similar to those of the prostate tissues. The differences between the immortal prostate cancer cell lines and prostate tissue are of sufficient magnitude to suggest that in vitro results with cell lines may not extrapolate to prostate cancer in vivo. The GSH content and GST activity in a prostate specific antigen-secreting human prostate tumor xenograft, LuCaP23, maintained in nude mice were similar to those of human prostate tissue and primary cultures. Both the xenograft and primary cultures from patients with prostate cancer may be more appropriate models than established cell lines for investigating techniques to increase the effectiveness of alkylators in prostate cancer.

    Title Knowledge, Beliefs, and Prior Screening Behavior Among Blacks and Whites Reporting for Prostate Cancer Screening.
    Date October 1995
    Journal Urology
    Excerpt

    OBJECTIVES. A survey to determine prostate cancer-related knowledge, beliefs, and prior screening behavior was administered to men participating in prostate cancer screening events at nine major sites in the southeast. Since prostate cancer disproportionately affects blacks, a primary focus of the analysis was to determine if differences in responses exist between racial groups. METHODS. A 20-question, multiple-choice survey to ascertain prostate cancer knowledge and beliefs, demographics, and health care access information was administered at nine major southeastern sites participating in Prostate Cancer Awareness screening events. Potential differences between the responses of blacks and whites were tested using the Cochran-Mantel-Haenszel test (P < 0.05), adjusting for differences among sites. RESULTS. Major findings of this study on 286 black and 1218 white men are as follows: (1) only 28% of black or white men report that their doctor ever discussed a test for prostate cancer with them; (2) blacks were less likely to have a regular doctor (P = 0.03) or ever to have had a digital rectal examination (P < 0.001) or prostate-specific antigen testing (P = 0.005); (3) blacks were less likely to report knowing someone with prostate cancer (P < 0.001) and were more apt to report their acquaintances experiencing post-treatment impotence than whites (P = 0.03); they were less likely to report that "a man with prostate cancer can lead a normal life" (P < 0.001) or that "men can have prostate cancer without symptoms" (P < 0.001); (4) a substantial number of all men did not know that race and/or heredity are risk factors; and (5) "peace of mind" was the leading reason why men (63% of whites and 50% of blacks) attended prostate cancer screening events. CONCLUSIONS. There are a number of similarities among black and white men regarding knowledge and beliefs related to prostate cancer. Important differences, however, in access to screening, perception of the disease and its treatment, and knowledge of risk factors exist between racial groups and represent significant barriers to early detection among African Americans.

    Title Adjuvant Radiotherapy for Pathologic Stage T3/4 Adenocarcinoma of the Prostate: Ten-year Update.
    Date September 1995
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To determine the role of adjuvant postoperative radiotherapy (RT) following radical prostatectomy (RP) in a group of patients with pathologic Stage T3/4 adenocarcinoma of the prostate followed for a median of 10 years after treatment. METHODS AND MATERIALS: Between 1970 and 1983, 159 patients underwent RP for newly diagnosed adenocarcinoma of the prostate and were found to have pathologic Stage T3/4. Forty-six received adjuvant RT and 113 did not. Radiotherapy usually consisted of 45-50 Gy to the whole pelvis followed by a boost to the prostate bed of 10-15 Gy, to a total dose of 55-65 Gy. Patients were analyzed with respect to survival, disease-free survival, local control, and freedom from distant metastases. A rising prostate-specific antigen in the absence of other evidence of relapse was scored as a separate category of recurrence. RESULTS: Both groups of patients have been followed for a median of 10 years. The actuarial survival at 10 and 15 years was 62% and 62% for the RT group compared to 52% and 37%, respectively, for the RP group (p = 0.18). The disease-free survival for the Rt group was 55% and 48% at 10 and 15 years, respectively, compared to 37% and 33% for the RP group (p = 0.16). Similarly, there was no difference in the rate of distant metastases between the two groups. In contrast, the local relapse rate was significantly reduced by the addition of postoperative radiotherapy. The actuarial local control rate at 10 and 15 years was 92% and 82%, respectively, for the RT group vs 60% and 53% for the RP group (p = 0.002). CONCLUSIONS: While postoperative pelvic RT significantly improves local control compared to RP alone for pathologic Stage T3/4 prostate cancer, it has no impact on distant metastases and consequently does not improve survival. These data are consistent with the conclusion that many patients with pathologic Stage T3/4 prostate cancer have occult metastases at presentation and will not be cured by local therapies alone. The optimal treatment for this patient population remains to be established.

    Title 6-methylene Progesterone is Cytotoxic to Human Cancer Cell Lines Independent of Its 5-alpha-reductase Activity.
    Date March 1995
    Journal The Prostate
    Excerpt

    This investigation examined the effects of 6-methylene progesterone (6MP), an irreversible inhibitor of 5-alpha-reductase, on prostatic cancer (PC) cell lines. Dose titration microculture tetrazolium assays were used to evaluate cytotoxicity in cultures treated for 72 hr with 6MP (0-20 micrograms/ml). An androgen-sensitive cell line, LNCaP, was drug-sensitive with a mean 50% lethal dose value (LD50) of 2.632 +/- 0.103. Hormone-resistant PC cell lines 1-LN, DU 145, and PC3 also demonstrated sensitivity with LD50 values between 0.8579-1.110 micrograms/ml with a group average of 1.023 +/- 0.082 micrograms/ml. Increasing dosages of dihydrotestosterone in the growth media did not alter 6MP cytotoxicity in androgen-insensitive prostatic cancer cell lines. No correlation between androgen-responsiveness and 6MP-induced cytotoxicity was observed. In nonprostatic malignancies, 6MP inhibited adenocarcinoma cell lines with a mean group LD50 value of 0.7772 micrograms/ml +/- 0.110. J82, a transitional cell carcinoma cell line of bladder origin, exhibited an average LD50 value of 1.041 +/- 0.260. In an epidermoid cervical cancer cell line, ME180, an LD50 value of 0.5356 micrograms/ml +/- 0.010 was noted. In a melanoma cell line, Du Mel 6, a mean LD50 of 0.7428 +/- 0.023 micrograms/ml was achieved with 6MP. We conclude that 6MP, a novel 5-alpha-reductase inhibitor, has potential as a cytotoxic agent in prostatic carcinoma and additional human malignancies. Further study is justified.

    Title Differential Immunoreactivity of Transforming Growth Factor Alpha in Benign, Dysplastic and Malignant Prostatic Tissues.
    Date February 1995
    Journal Surgical Oncology
    Excerpt

    Immunohistochemical examination of radical prostatectomy specimens from 57 patients was performed to determine the differential expression of transforming growth factor alpha in the human prostate. In addition, epidermal growth factor receptor (EGFr) immunoreactivity was assessed in each case. Stromal versus epithelial staining was determined for each histological subtype: benign prostatic hypertrophy (BPH), prostatic intra-epithelial neoplasia (PIN), and prostatic cancer (CaP) by a single pathologist reviewer. TGFa staining was predominant in stroma while EGFr was localized to the epithelial basal cell layer. Immunoreactivity of both TGFa (P = 0.002) and EGFr (P < 0.001) revealed a significant reduction in CaP compared to BPH or PIN. Autocrine stimulation of EGFr by TGFa or other unrecognized factors may be present in CaP. Conversely, altered stromal influence of CaP via TGFa may be present. These observations could form the basis for future cancer therapeutic strategies using antagonist factors.

    Title Differential Immunoreactivity of Her-2/neu Oncoprotein in Prostatic Tissues.
    Date January 1994
    Journal Surgical Oncology
    Excerpt

    To investigate HER-2/neu oncoprotein immunoreactivity, monoclonal antibody TA1 immunohistochemical examination of flash-frozen radical prostatectomy specimens was performed (n = 35). All prostatic specimens contained benign prostatic hyperplasia (BPH) and/or prostatic intraepithelial neoplasia (PIN), as well as prostatic carcinoma (CaP). HER-2/neu oncoprotein immunoreactivity in BPH tissues was not significantly different than that for the PIN basal cell layer (P = 0.10) or for the PIN luminal cells (P = 0.17). There was significantly more HER-2/neu oncoprotein immunoreactivity in BPH than in areas of CaP (P < 0.001). There was no significant difference in the amount of immunoreactivity present in PIN basal cells when compared to the PIN luminal cells (P = 0.49). Both the PIN basal cells and luminal cells stained for the HER-2/neu oncoprotein to a higher degree than cells in the CaP areas (P < 0.001 in both cases). HER-2/neu oncoprotein immunoreactivity is present at a significantly higher degree in BPH and PIN than in malignant prostatic epithelium.

    Title Characteristics of Men Reporting for Prostate Cancer Screening.
    Date October 1993
    Journal Urology
    Excerpt

    A survey to determine demographics, prostate cancer screening practices, and prostate cancer-related knowledge and beliefs was administered to over 1,700 participants at five sites during Prostate Cancer Awareness Week (1991) screening events. Findings are presented by site since significant differences in demographics existed. Results suggest that screenings conducted at the major medical centers attract primarily white males, a number of whom already practice adequate secondary prevention. Thus, if optimal benefit is sought through mass prostate cancer screening, innovative strategies to reach populations that are currently underserved and at risk are necessary.

    Title Genetic Risk and Carcinogen Exposure: a Common Inherited Defect of the Carcinogen-metabolism Gene Glutathione S-transferase M1 (gstm1) That Increases Susceptibility to Bladder Cancer.
    Date August 1993
    Journal Journal of the National Cancer Institute
    Excerpt

    BACKGROUND: Numerous studies have associated bladder cancer with exposure to carcinogens present in tobacco smoke and other environmental or occupational exposures. Approximately 50% of all humans inherit two deleted copies of the GSTM1 gene which encodes for the carcinogen-detoxification enzyme glutathione S-transferase M1. Recent findings suggest that the GSTM1 gene may modulate the internal dose of environmental carcinogens and thereby affect the risk of developing bladder cancer. PURPOSE: We investigated whether the absence of the GSTM1 gene affects bladder cancer risk and whether there are racial differences in GSTM1 genotype frequency. METHODS: Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the homozygous deleted genotype (GSTM1 0/0) in 229 patients with transitional cell carcinoma of the bladder and 211 control subjects who were enrolled from the Urology Clinics at Duke University Medical Center and the University of North Carolina Hospitals. Control subjects were urology clinic patients who primarily presented with benign prostatic hypertrophy or impotence, who had no history of any cancer other than nonmelanoma skin cancer, and who were frequency matched to case patients on race, sex, and age (10-year age intervals). In order to explore racial differences in GSTM1 gene frequency, genotype was also determined in a community-based sample of 466 paid, healthy, unrelated volunteers from Durham and Chapel Hill, N.C. The presence or absence of the GSTM1 gene locus was determined by using a differential PCR, a semiquantitative technique in which multiple genes are coamplified. RESULTS: Overall, the GSTM1 0/0 genotype conferred a 70% increased risk of bladder cancer (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.5; P = .004). Absence of the GSTM1 gene encoding the glutathione S-transferase M1 enzyme significantly increased risk to persons with exposure to the carcinogens in tobacco smoke (OR = 1.8; 95% CI = 1.2-3.0; P = .01) but poses little increased risk to persons without such exposure. Persons with smoking exposure of more than 50 pack-years who had the GSTM1 0/0 genotype had a sixfold greater risk relative to persons in the lowest risk group (i.e., nonsmokers who were GSTM1 +/+ or +/0). In the pooled clinic control and community sample groups (677 individuals), the GSTM1 0/0 genotype occurred less frequently among Blacks (35%) than among Whites (49%, P < .001). CONCLUSIONS: These findings support a protective role for the GSTM1 gene in bladder cancer. From these findings, it is estimated that 25% of all bladder cancer may be attributable to the at-risk GSTM1 0/0 genotype.

    Title Differential Immunoreactivity of Epidermal Growth Factor Receptor in Benign, Dysplastic and Malignant Prostatic Tissues.
    Date January 1993
    Journal The Journal of Urology
    Excerpt

    To investigate epidermal growth factor receptor (EGFr) presence in the prostate, monoclonal antibody (clone EGFR1) immunohistochemical examination of radical prostatectomy specimens was performed (n = 37). All prostatic specimens contained benign prostatic hyperplasia (BPH) and/or dysplasia (prostatic intraepithelial neoplasia or PIN), as well as prostatic carcinoma (CaP). Areas of dysplasia were further categorized as to the basal cell layer and the luminal cell area. BPH, PIN, and CaP tissues in each specimen were analyzed by a single observer and graded on a scale from 0-4+. Fifteen samples were also analyzed for EGFr content utilizing a Cell Analysis Systems (CAS 200) image cytometer. EGFr immunoreactivity of BPH basal cells was significantly higher than EGFr immunoreactivity in areas of CaP (p < 0.001). EGFr staining of BPH basal cells was also significantly higher than that seen in PIN luminal cells (p < 0.001). Immunoreactivity of EGFr in PIN basal cells was significantly higher than in PIN luminal cells (p < 0.001). EGFr staining of basal cells in BPH tissues was higher than that seen in the PIN basal cell layer but the difference was not statistically significant (p = 0.06). The amount of staining present in PIN luminal cells was also significantly greater than in CaP tissues (p = 0.002). Quantitative image analysis utilizing the CAS 200 image cytometer was performed on BPH and CaP areas exclusively. EGFr immunoreactivity in basal cells of the BPH tissues was significantly greater than that seen in CaP tissues (p < 0.001). The decreased EGFr immunoreactivity in CaP may reflect a differentiating role for EGFr in normal tissues. Loss of EGFr influence may be associated with an increased proliferative state in PIN and CaP. Destruction or alteration of the epidermal grwoth factor receptor by a protease, such as prostatic specific antigen, may also explain our findings. At the present time the meaning of the different amounts of EGFr in the various types of prostate tissues is unknown.

    Title Detection of Human Papillomavirus in the Prostate by Polymerase Chain Reaction and in Situ Hybridization.
    Date December 1992
    Journal The Journal of Urology
    Excerpt

    Human papillomavirus is associated with a variety of anogenital lesions, including genital warts, precancers and cancers. In male patients human papillomavirus has been identified in proliferative lesions ranging from penile and urethral warts to penile and prostatic cancers. We examined the association of human papillomavirus deoxyribonucleic acid (DNA) in 84 prostate tissue specimens. Specimens were selected from radical prostatectomy, transurethral resection or transrectal biopsy procedures. A total of 60 formalin-fixed, paraffin-embedded tissues (24 prostate cancer specimens, 16 benign prostatic hyperplasia specimens and 20 normal specimens) was examined by polymerase chain reaction and in situ hybridization. Also, 24 gelatin-embedded frozen prostate cancer specimens were examined for human papillomavirus DNA by polymerase chain reaction. Of the specimens 69 were deemed adequate for polymerase chain reaction analysis, whereas all 60 paraffin-embedded tissues were sufficient for in situ hybridization. Human papillomavirus DNA was detected in 2 normal tissues and 6 prostate cancers using polymerase chain reaction. None of the benign prostatic hyperplasia specimens was positive for human papillomavirus. Human papillomavirus typing results indicated that virus type 16 was present in each of the 8 positive specimens. Confirmation of the presence of human papillomavirus was obtained for 1 of the prostate cancers by nonisotopic in situ hybridization with biotinylated human papillomavirus genomic probes. The low prevalence of human papillomavirus in this study population does not strongly support an etiological role for the virus in prostate cancer.

    Title Body Dimension Differences in Men with or Without Prostate Cancer.
    Date September 1992
    Journal Journal of the National Cancer Institute
    Title Dna in Radical Prostatectomy Specimens. Prognostic Value of Tumor Ploidy.
    Date June 1991
    Journal Acta Oncologica (stockholm, Sweden)
    Excerpt

    In a series of 94 patients with prostatic adenocarcinoma the prognostic significance of some factors was studied after radical prostatectomy. DNA ploidy was assessed by flow cytometry of cells from deparaffinized specimens. Gleason sum, seminal vesicle status and ploidy turned all out to be important predictors of disease progression. The ploidy status significantly enhanced the ability to prognostically evaluate patients with intermediate grade carcinoma compared to tumor grade alone. Patients with seminal vesicle invasion and aneuploidy had a very poor prognosis which prompts trials with alternatives of adjuvant therapy in this patient population.

    Title The Relevance of Stage A Malignancy in Prostatic Cancer.
    Date June 1991
    Journal Acta Oncologica (stockholm, Sweden)
    Excerpt

    Patients with T1 (stage A) prostatic cancer detected on transurethral resection and patients with T2 (stage B) cancer, identified by palpation and needle biopsy, had similar time to failure and survival following radical prostatectomy. Transurethral resection was not associated with a higher degree of failure. The volume of the tumor and the biology of the disease were decisive of the outcome. In low-grade low-volume prostatic adenocarcinoma the risk of progression is very low.

    Title Radical Surgery Versus Radiation Therapy in Early Prostatic Carcinoma.
    Date June 1991
    Journal Acta Oncologica (stockholm, Sweden)
    Excerpt

    Patients with organ-confined prostatic cancer, as determined by digital examination, bone scans and serum acid phosphatase determination, were randomized to radical prostatectomy or external-beam radiation therapy. With respect to first evidence of treatment failure, there was a significant difference in favor of the patients who had surgical treatment. In the patients given radiotherapy there was no essential difference in time to failure as compared with comparable patients in two recent observation-only trials on record.

    Title Positive Margins: is Adjunctive Radiation Therapy Indicated?
    Date June 1991
    Journal Acta Oncologica (stockholm, Sweden)
    Excerpt

    Patients with margin positive disease after radical prostatectomy are prognostically disadvantaged. The question of postoperative adjunctive radiotherapy in these patients is controversial. A retrospective study suggested that adjunctive radiation therapy reduced the local recurrence rate but did not alter survival.

    Title Surgical Management of Pheochromocytoma with the Use of Metyrosine.
    Date December 1990
    Journal Annals of Surgery
    Excerpt

    Despite recommended preoperative preparation with alpha-adrenergic blockers, severe hemodynamic instability may occur during operations to resect pheochromocytoma. We combined the alpha-blocker phenoxybenzamine with the tyrosine hydroxylase inhibitor metyrosine in an attempt to better manage the hypertension of patients with pheochromocytoma undergoing surgical resection. This report reviews the cases of 25 consecutive patients undergoing surgery for known intra-abdominal pheochromocytoma. Each patient had elevated serum or urine levels of catecholamines or their metabolites. Nineteen patients were prepared before operation with phenoxybenzamine and metyrosine and six patients were given phenoxybenzamine alone. There were no significant differences in maximum, minimum, or mean blood pressure before or after tumor resection between patients who received metyrosine and those who did not. However careful review suggested that those who received metyrosine had more severe disease as judged by biochemical criteria. Study of selected patients matched for age and severity of disease suggested that the intraoperative blood pressure management of patients prepared with phenoxybenzamine and metyrosine was facilitated. In addition metyrosine-prepared patients lost less blood and required less volume replacement during surgery than did non-metyrosine-prepared patients. There were no apparent differences in postoperative fluid requirements. Although the study is not a prospective randomized trial, a retrospective review of patients managed with the combination of phenoxybenzamine and metyrosine suggests that surgery to resect pheochromocytoma can be better performed with both drugs than with phenoxybenzamine alone. The combination regimen appears to result in better blood pressure control, less blood loss, and the need for less intraoperative fluid replacement than does the traditional method of single-agent alpha-adrenergic blockade.

    Title Preparative Cytoreductive Surgery in Patients with Metastatic Renal Cell Carcinoma Treated with Adoptive Immunotherapy with Interleukin-2 or Interleukin-2 Plus Lymphokine Activated Killer Cells.
    Date September 1990
    Journal The Journal of Urology
    Excerpt

    A total of 63 patients with metastatic renal cell carcinoma with the primary kidney tumor in place was accepted as candidates for immunotherapy at the Surgery Branch of the National Cancer Institute. Of the 63 patients 54 underwent nephrectomy and 9 were treated with the primary kidney tumor in place. Many of the patients underwent associated procedures, such as regional lymphadenectomy (11), venacavotomy with extraction of tumor thrombus (9), hepatic resection (2), pulmonary wedge resection (2), cholecystectomy (2), splenectomy (2), distal pancreatectomy (1), omentectomy (1) and contralateral adrenalectomy (1). Of the 54 patients 20 were not able to enter therapy because of tumor-related (17) or other medical (3) reasons that developed between the operation and therapy, while 34 were able to receive immunotherapy postoperatively. The 20 patients who were treated with either high dose interleukin-2 or interleukin-2 plus lymphokine activated killer cells soon postoperatively (mean 2.1 months) were able to tolerate roughly the same amount of interleukin-2 as the 74 who had undergone nephrectomy before referral to our institute and who were treated for a mean of 22 months after nephrectomy. Further studies, including a prospective, randomized trial, will be required to define the role of nephrectomy in patients with advanced renal cell carcinoma before treatment with interleukin-2 based immunotherapies.

    Title Collecting Duct Carcinoma of the Kidney.
    Date May 1990
    Journal Human Pathology
    Excerpt

    Collecting duct carcinoma is an unusual variant of renal cell carcinoma, whose appearance and behavior are not well established. We identified six cases of collecting duct carcinoma in our files. The clinical, pathologic, and immunohistochemical characteristics of these tumors are reported. The most common symptom was gross hematuria (four cases). Two patients had cervical adenopathy due to metastatic tumor. Four rapidly developed systemic metastases and died within 4 to 24 months. The primary renal tumors were located predominantly in the renal medulla and pelvis and had a partially cystic white-gray appearance. Histologic examination showed prominent tubulopapillary structures, nests of clear cells, and infiltrating tubules in a dense desmoplastic stroma. Atypical hyperplastic changes were found in some of the adjacent collecting ducts. Mucicarminophilic material was present in glandular elements in all six cases. Immunohistochemical studies revealed positivity with antibodies to epithelial membrane antigen, keratins, peanut agglutinin, vimentin, Leu M1 and lysozyme. The location of this tumor in the medulla, its distinctive histologic appearance, mucin positivity, expression of high molecular weight cytokeratins, and peanut agglutinin suggest that this is a distinct clinicopathologic entity which has an aggressive clinical course.

    Title Epidermal Growth Factor Receptor Gene Analysis in Renal Cell Carcinoma.
    Date February 1990
    Journal The Journal of Urology
    Excerpt

    The epidermal growth factor receptor binds the mitogens epidermal growth factor and transforming growth factor-alpha. Increased expression of the epidermal growth factor receptor has been noted in many types of tumors and is associated with gene amplification in several including epidermoid carcinoma, lung carcinoma, breast carcinoma and glioblastoma. We have recently observed increased expression of the epidermal growth factor receptor messenger RNA in neoplastic tissue relative to normal kidney tissue from patients with renal cell carcinoma. To determine if epidermal growth factor receptor gene amplification was present in renal cell carcinoma, DNA was extracted from renal cell carcinoma cell lines and from normal kidney and renal cell carcinoma tissues derived from radical nephrectomy specimens from thirty patients. DNA was analyzed by Southern blot hybridization. There was no epidermal growth factor receptor gene amplification detected in the renal cell carcinoma samples studied, indicating the increased epidermal growth factor gene expression observed in renal cell carcinoma does not occur through gene amplification. Unlike other tumors with enhanced epidermal growth factor receptor gene expression, amplification of this gene does not appear to be a common feature of renal cell carcinoma.

    Title The Detection of Renal Carcinoma Extension into the Renal Vein and Inferior Vena Cava: a Prospective Comparison of Venacavography and Magnetic Resonance Imaging.
    Date October 1989
    Journal The Journal of Urology
    Excerpt

    Accurate preoperative evaluation of the inferior vena cava and renal vein in patients with renal cell carcinoma is mandatory to plan a successful surgical approach. The presence of venous extension may alter transfusion and anesthetic requirements, as well as require the addition of a vascular surgeon to the operative team. Venacavography traditionally has been considered the most reliable method to identify tumor thrombus, although magnetic resonance imaging has been proposed as a possible noninvasive alternative. We compared prospectively the accuracy of these 2 methods in 44 consecutive patients with renal cell carcinoma who subsequently underwent nephrectomy. Of the 44 patients 11 (25%) had tumor extension into the inferior vena cava and 17 (39%) had involvement of the renal vein at operation. Venacavography and magnetic resonance imaging correctly identified 9 of the 11 patients (82%) with inferior vena caval thrombus. When the results of both tests were combined, all 11 cases of vena caval extension were identified. Venacavography was slightly more sensitive (71%) in identifying the presence of renal vein thrombus than magnetic resonance imaging (65%) but these differences were not statistically significant. Magnetic resonance imaging better localized the thrombus within the renal vein. We conclude that venacavography and magnetic resonance imaging offer equal diagnostic accuracy in the identification of venous extension of renal cell carcinoma. The combination of both tests results in higher diagnostic yield than either test alone. Neither test by itself is reliable in the presence of a large, bulky adenopathic lesion that compresses the inferior vena cava.

    Title Genetic Changes in Human Adrenocortical Carcinomas.
    Date April 1989
    Journal Journal of the National Cancer Institute
    Excerpt

    Recent studies have suggested that loss of heterozygosity at loci on the short arm of human chromosome 11 (11p) may be important in the pathogenesis of benign and malignant adrenal cortical tumors. To test this concept, adrenocortical carcinomas from nine patients and benign adrenal cortical lesions from eight patients were tested for loss of alleles at loci on human chromosomes 11, 13, and 17. All patients with adrenocortical carcinoma whose normal somatic tissues were heterozygous for a locus on chromosome 17p had lost alleles in the tumor. Four of six patients with adrenocortical carcinoma who were heterozygous for one or more alleles on chromosome 11p in normal tissues had lost 11p alleles in the tumor. Three of six patients with adrenocortical carcinoma showed loss of 13q alleles in the tumor. Loss of alleles on chromosomes 11p, 13q, and 17p was observed in primary tumors and metastases but not in adrenocortical adenomas or hyperplastic lesions of the adrenal cortex. One patient with adrenocortical carcinoma had a somatic mutation in the HRAS1 gene in the normal adrenal gland. The consistency of the genetic changes on chromosomes 11p, 13q, and 17p suggests that they are important in the pathogenesis of adrenocortical carcinoma.

    Title The Inhibition of Human Adrenal Steroidogenic Enzyme Activities by Suramin.
    Date March 1989
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    Suramin has recently been used to treat patients with acquired immune deficiency syndrome because of the action of this drug on reverse transcriptase. Patients so treated developed the symptoms and hormonal profiles of adrenal insufficiency. To evaluate the mechanism of action of suramin on adrenalcortical function, adrenal mitochondrial and microsomal preparations from five subjects were assayed for steroidogenic enzyme activity in the presence and absence of suramin. Specifically, 3 beta-hydroxysteroid dehydrogenase/isomerase, 17 alpha-hydroxylase, 21-hydroxylase, 11 beta-hydroxylase, and 17,20-desmolase activities were measured in the presence of 0-5000 mumol/L suramin concentrations. In all assays, enzyme activities decreased in a dose-dependent fashion as suramin concentrations increased. The drug doses (calculated) that caused 50% inhibition of enzyme activity were: 21-hydroxylase activity, 50 mumol/L; 17 alpha-hydroxylase activity, 25 mumol/L; 17,20-desmolase activity, 50 mumol/L; 11 beta-hydroxylase, 2 mumol/L, and 3 beta-hydroxysteroid dehydrogenase/isomerase, 1200 mumol/L. These results suggest that suramin has a concentration-dependent inhibitory effect on the key P-450-regulated enzymatic steps in adrenal glucocorticoid steroidogenesis, which may explain the development of adrenal insufficiency in acquired immune deficiency syndrome patients treated with suramin.

    Title Evaluation of the Paracrine and Endocrine Effects of Genitourinary Tumor Produced Growth Factors.
    Date November 1988
    Journal Progress in Clinical and Biological Research
    Title Fournier Gangrene: Diagnosis with Scrotal Us.
    Date November 1988
    Journal Radiology
    Excerpt

    Skin thickening and subcutaneous air were detected at ultrasound (US) of the scrotum in a patient with normal-appearing testicles and signs and symptoms suggestive of an acute inflammatory process, such as epidydimitis or orchitis. The patient was found to have Fournier gangrene. In more advanced cases, US can demonstrate that this skin thickening and subcutaneous air extends posteriorly to include the perineum and buttocks. Because of the high mortality of this mixed anaerobic and aerobic infection, it is important to recognize Fournier gangrene early so that the correct surgical and medical treatment can be promptly instituted. To the authors' knowledge, this is the first description of the US characteristics of Fournier gangrene.

    Title Immunotherapy of Patients with Advanced Cancer Using Tumor-infiltrating Lymphocytes and Recombinant Interleukin-2: a Pilot Study.
    Date June 1988
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    Clinical investigations using the adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) to treat patients with advanced cancer have yielded encouraging results. We have thus sought ways to enhance the effectiveness of adoptive immunotherapy while minimizing its toxic side effects. Murine experiments have identified tumor-infiltrating lymphocytes (TIL) as killer cells more effective than LAK cells and less dependent on adjunctive systemically administered IL-2 to mediate antitumor effects. Accordingly, we performed a pilot protocol to investigate the feasibility and practicality of administering IL-2-expanded TIL to humans with metastatic cancers. Twelve patients, including six with melanoma, four with renal cell carcinoma, one with breast carcinoma, and one with colon carcinoma, were treated with varying doses and combinations of TIL (8.0 X 10(9) to 2.3 X 10(11) cells per patient), IL-2 (10,000 to 100,000 U/kg three times daily to dose-limiting toxicity), and cyclophosphamide (CPM) (up to 50 mg/kg). Two partial responses (PR) to therapy were observed: pulmonary and mediastinal masses regressed in a patient with melanoma, and a lymph node mass regressed in a patient with renal cell carcinoma. One additional patient with breast cancer experienced a partial regression of disease in lymph nodal and cutaneous sites with complete elimination of malignant cells from a pleural effusion, although cutaneous disease recurred at 4 weeks. The toxicities of therapy were similar to those ascribed to IL-2; no toxic effects were directly attributable to TIL infusions. In five of six melanoma patients, TIL demonstrated lytic activity specific for the autologous tumor target in short-term chromium-release assays, distinct from the nonspecific lytic activity characteristic of LAK cells. This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.

    Title Late Hematogenous Infection of Penile Prostheses.
    Date January 1988
    Journal The Journal of Urology
    Excerpt

    Late deep wound infection caused by hematogenous bacterial spread from a remote focus is a rare but disastrous complication of prosthetic devices. Six patients with probable late hematogenous infection are described. The initial implantation was free of contamination and infection, and a long functional interval ensued. A febrile process associated with a painful, swollen penis followed a probable remote infection source that was not covered with prophylactic antibiotics. All prostheses required removal. Prophylactic antibiotics may prevent these late hematogenous infections.

    Title A Progress Report on the Treatment of 157 Patients with Advanced Cancer Using Lymphokine-activated Killer Cells and Interleukin-2 or High-dose Interleukin-2 Alone.
    Date April 1987
    Journal The New England Journal of Medicine
    Excerpt

    We studied the effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells plus interleukin-2 or therapy with high-dose interleukin-2 alone in 157 patients with metastatic cancer for whom standard therapy had proved ineffective or no standard effective treatment was available. One hundred eight patients were treated with 127 courses of LAK cells plus interleukin-2, and 49 patients were treated with 53 courses of high-dose interleukin-2 alone. Of 106 evaluable patients receiving LAK cells plus interleukin-2, 8 had complete responses, 15 had partial responses, and 10 had minor responses. The median duration of response was 10 months among those with complete responses and 6 months among those with partial responses; the patient with the longest complete response was still in remission 22 months after treatment. Of 46 evaluable patients treated with high-dose interleukin-2 alone, 1 had a complete response (remission greater than 4 months), 5 had partial responses (2, greater than 3, greater than 5, 7, and greater than 11 months), and 1 had a minor response. Seven of the total of nine complete responses still remain in remission. Hypotension, weight gain, oliguria, and elevation of bilirubin and creatinine levels were common, but these side effects resolved promptly after interleukin-2 administration was stopped. There have been four treatment-related deaths among these 157 patients. This immunotherapeutic approach can result in marked tumor regression in some patients for whom no other effective therapy is available at present. Determining its ultimate role in cancer therapy awaits further attempts to increase the therapeutic efficacy of treatment and decrease its toxicity and complexity.

    Title Use of the Rectus Abdominis Muscle Flap in Urological Reconstructive Procedures.
    Date May 1986
    Journal The Journal of Urology
    Excerpt

    The rectus abdominis muscle flap has been used successfully in 4 reconstructive procedures complicated by tissue loss or urinary fistula. This simple procedure is advocated as an alternative to the use of omentum when prior abdominal surgery precludes omental mobilization. No adverse functional nor cosmetic result to the abdominal wall resulted.

    Title Bladder Substitution in Children.
    Date May 1986
    Journal The Urologic Clinics of North America
    Excerpt

    In spite of all the difficulties, cystoplasty, particularly with the ileocecal segment, has proved rewarding. Undiversion is easily accomplished in this way. Most patients are outwardly well and happy. Reflux usually does no harm in the near term, especially if infection can be prevented, and bladder pressures are not elevated. However, we believe that we are close to being able to prevent reflux in a reliable manner. If this is the case, the ileocecal segment or hemi-Kock pouch may clearly become the optimal choice for bladder substitution in patients with reflux or ureteral obstruction, as well as those with short ureters or very small bladders, or as a standard method of undiversion. We have also employed the intussuscepted ileum as the antireflux mechanism in patients undergoing bladder substitution using a patch of small bowel as in the hemi-Kock. This technique allows one to leave the cecum and ileocecal valve in situ, reducing the risk of chronic postoperative diarrhea. In addition, small bowel is proving to be more compliant on the average than large bowel segments when used in bladder reconstruction. Whether the ileocecal segment or the hemi-Kock cystoplasty has a permanent place in undiversion and in the treatment of chronic or pharmacoresistant noncompliant bladder, neuropathic or otherwise, the techniques learned are making total replacement of the bladder with bowel segments a more attractive and feasible undertaking. The pool of patients susceptible to such maneuvers is a large one.

    Title Lethal Complications of Standard Self-retaining Ureteral Stents in Patients with Ileal Conduit Urinary Diversion.
    Date May 1985
    Journal The Journal of Urology
    Excerpt

    While standard commercially available pigtail ureteral stents are used commonly in the obstructed patient, particularly when metastatic disease has been identified, our recent experience suggests caution in the use of such stents for patients with ileal conduits. Rapid obstruction of these stents occurs with unacceptable frequency, which has resulted in urosepsis and death, and they do not appear to be cost-effective even for palliation. Although these standard pigtail stents have physical properties that allow easy placement by angiographic wire guidance, they are not to be recommended. Safe internal ureteral diversion in patients with an ileal conduit awaits further evolution in stent technology.

    Title The Vascularized Skin Island Urethroplasty: Its Role and Results in Urethral Stricture Management.
    Date January 1985
    Journal The Journal of Urology
    Excerpt

    We report 11 vascularized island skin flap urethroplasties. Results appear to be excellent when the procedure is used for strictures of the pendulous urethra. Use of vascularized skin flap urethroplasties for the repair of bulbar and membranous strictures has been complicated by pseudodiverticula and stone formation, and in this portion of the urethra the technique probably should be reserved for cases in which local factors mitigate against alternative 1-stage procedures.

    Title Race and Prostate Weight As Independent Predictors for Biochemical Recurrence After Radical Prostatectomy.
    Date
    Journal Prostate Cancer and Prostatic Diseases
    Excerpt

    We hypothesized that factors beyond pathological stage, grade, PSA and margin status would be important predictors of biochemical recurrence (BCR) after radical prostatectomy (RP). A cohort of 3194 patients who underwent RP between 1988 and 2007 and who had neither neoadjuvant therapy nor postoperative adjuvant hormonal therapy was retrieved from the Duke Prostate Center database. Age, prostate-specific antigen (PSA), pathological Gleason score (pG), lymph node status, seminal vesicle invasion (SVI), extracapsular extension (ECE), positive surgical margin (PSM) status, year of surgery, race, adjuvant radiation therapy (XRT), percent tumor involvement in the RP specimen and prostate weight were evaluated as possible predictors of BCR in multivariate Cox regression analysis. BCR was defined as a PSA of 0.2 ng ml(-1) or higher at least 30 days after surgery. A nomogram was developed from the Cox model. Predictive accuracy was obtained by calculating bias-corrected Harrell's c and by bootstrap calibration. In multivariate analysis, PSA (hazard ratio 1.39 (95% confidence interval 1.29-1.51)), ECE (1.22 (1.04-1.44)), pG score (1.38 (1.14-1.68), 2.23 (1.76-2.84), 2.69 (2.12-3.40) for pG 3+4, 4+3, >7, respectively), SVI (1.72 (1.40-2.12)), PSM (2.05 (1.73-2.42)), year of surgery (0.65 (0.54-0.77)), African-American race (1.37 (1.13-1.66)), adjuvant XRT (0.19 (0.11-0.34)) and prostate weight (0.83 (0.76-0.92)) were identified as independent predictors of BCR (P</=0.018 for all factors). Predictive accuracy of the nomogram was 0.75. Race and prostate weight were independent predictors for BCR after RP. By incorporating these variables, we developed a nomogram, which provides a highly accurate means for estimating risk of BCR after RP.Prostate Cancer and Prostatic Diseases advance online publication, 22 April 2008; doi:10.1038/pcan.2008.18.

    Title Satisfaction and Regret After Open Retropubic or Robot-assisted Laparoscopic Radical Prostatectomy.
    Date
    Journal European Urology
    Excerpt

    BACKGROUND: To counsel patients adequately, it is important to understand the variables influencing satisfaction and regret following prostatectomy. OBJECTIVE: To identify independent predictors for satisfaction and regret after radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Patients who had undergone retropubic radical prostatectomy (RRP) or robot-assisted laparoscopic radical prostatectomy (RALP) between 2000 and 2007 were mailed cross-sectional surveys composed of sociodemographic information, the Expanded Prostate Cancer Index Composite (EPIC), and questions regarding satisfaction and regret. MEASUREMENTS: Sociodemographic variables, perioperative complications, type of procedure, length of follow-up, and EPIC scores were evaluated as independent predictors of satisfaction and regret in multivariate logistic regression analysis. RESULTS AND LIMITATIONS: A total of 400 patients responded (response rate 61%) of whom 84% were satisfied and 19% regretted their treatment choice. In multivariate analysis, lower income (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.03-0.23), shorter follow-up (OR, 0.63; 95% CI, 0.41-0.98), having undergone RRP versus RALP (OR, 4.45; 95% CI, 1.90-10.4)], urinary domain scores (OR, 2.70; 95% CI, 1.60-4.54), and hormonal domain scores (OR, 2.01; 95% CI, 1.30-3.12) were independently associated with satisfaction (p</=0.039). In terms of regret, RALP versus RRP (OR, 3.02; 95% CI, 1.50-6.07), lower urinary domain scores (OR, 0.58; 95% CI, 0.37-0.91) and hormonal domain scores (OR, 0.67; 95% CI, 0.45-0.98), and years since surgery (OR, 1.63; 95% CI, 1.13-2.36) were again predictive (p</=0.041). African American race (OR, 3.58; 95% CI, 1.52-8.43) and lower bowel domain scores (OR, 0.73; 95% CI, 0.55-0.97) were also independently associated with regret (p</=0.028). CONCLUSIONS: Sociodemographic variables and quality of life were important variables associated with satisfaction and regret. Patients who underwent RALP were more likely to be regretful and dissatisfied, possibly because of higher expectation of an "innovative" procedure. We suggest that urologists carefully portray the risks and benefits of new technologies during preoperative counseling to minimize regret and maximize satisfaction.

    Title Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery.
    Date
    Journal Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
    Excerpt

    BACKGROUND: Prostate cancer affects one of six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. METHODS: We undertook a multisite, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n = 161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: (a) control (usual diet), (b) flaxseed-supplemented diet (30 g/d), (c) low-fat diet (<20% total energy), or (d) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and before surgery and analyzed for prostate-specific antigen, sex hormone-binding globulin, testosterone, insulin-like growth factor-I and binding protein-3, C-reactive protein, and total and low-density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. RESULTS: Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67-positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) versus 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serologic endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P = 0.048). CONCLUSIONS: Findings suggest that flaxseed is safe and associated with biological alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.

    Title Prostate-specific Antigen Velocity Based Risk-adapted Discontinuation of Prostate Cancer Screening in Elderly Men.
    Date
    Journal Bju International
    Excerpt

    Study Type - Prognostic (cohort)
Level of Evidence 2b OBJECTIVE: To evaluate weather prostate-specific antigen (PSA) velocity could be used to stratify patients at risk of death from prostate cancer (PCa) and be useful in aiding decision making regarding PSA screening in elderly men, as previous studies have shown that PSA velocity can predict PCa risk. PATIENTS AND METHODS: The cohort included 3,525 patients aged ≥ 75 years with two or more PSA tests before a diagnosis of PCa. Cox proportional hazard model was used to evaluate which variables at time of last PSA measurement were associated with death from PCa. The rates of death from PCa after diagnosis in different PSA velocity groups were calculated. Kaplan-Meier and log rank test were used to assess the significant difference in death from PCa after diagnosis, stratified by PSA velocity cutoff. RESULTS: On multivariate analysis, men with a PSA velocity of PSA velocity ≥0.45 ng/mL/year had a 4.8-fold higher risk of death from PCa as compared to men with a PSA velocity of <0.45 ng/mL/year (p value = 0.013). After a median 6.5 (up to 16.9) years of follow-up from diagnosis, 1.4% of the men with a PSA velocity <0.45 ng/mL/year had died of PCa as compared to 8.7% of those with a PSA velocity ≥0.45 ng/mL/year. The cumulative rate of death from PCa after diagnosis, stratified by a PSA velocity of 0.45 ng/mL/year, was statistically different (log rank test, P < 0.001). CONCLUSION: Men age ≥ 75 years old with a PSA velocity of <0.45 ng/mL/year are unlikely to die of PCa. It may be safe to discontinue PSA screening in these men.

    Title Clinical Predictors of Renal Mass Pathological Features.
    Date
    Journal Bju International
    Excerpt

    Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Widespread use of abdominal imaging has changed the landscape of kidney lesions with an increase in serendipitously detected small renal masses (SRMs) that represent a new epidemiological entity that requires further understanding and potentially reconsideration of current treatment schemes. We identified specific preoperative factors associated with renal mass pathological features, and specifically with an increased risk of malignant, potentially aggressive disease. These factors should be considered when evaluating potential candidates for active surveillance and ablative techniques.

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