Racial differences in clinically localized prostate cancers of black and white men

PURPOSE: Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression were examined in clinically localized prostate cancers of black and white American men to learn whether these features showed racial differences. MATERIALS AND METHODS: A total of 117 prostate cancers (43 black and 74 white patients) obtained at radical prostatectomy for clinically localized disease were assigned Gleason scores by a single pathologist. Enzymatically dissociated nuclei from archival prostate cancers were examined by DNA flow cytometry using propidium iodide staining and the multicycle program to remove debris and sliced nuclei and to perform cell cycle analysis. For immunostaining after microwave antigen retrieval we used a DO-1/DO-7 monoclonal antibody cocktail for p53 and the clone 124 antibody for bcl-2. RESULTS: Significantly more black than white men had Gleason score 7 tumors. The DNA ploidy distribution of Gleason 6 or less tumors was similar for both races. As anticipated, the ploidy distribution of higher grade prostate cancer in white men was more abnormal but, unexpectedly, this was not found for higher grade prostate cancer in black men. No significant racial differences were found in S phase fractions, p53 or bcl-2 immunopositivity. However, for prostate cancer in black men there was a significant association between bcl-2 immunopositivity and higher S-phase fractions. CONCLUSIONS: The aggressive prostate cancers of black men may be characterized by the 2 features of high proliferation and a block to programmed cell death.     

Early tumor cell dissemination in patients with clinically localized carcinoma of the prostate

Death-associated protein kinase (DAP kinase) has been recently identified as a novel Ca2+/calmodulin-dependent protein kinase and as a potential mediator of gamma interferon-induced cell death of Hela cells, which has cytological characteristics of the programmed cell death. In order to elucidate its functional roles in the rat brain where the programmed cell death is an essential mechanism in the organization of postmitotic neurons during development, we cloned a rat homologue of the human DAP kinase from the rat embryonic brain cDNA library. The deduced amino acid sequence was highly conserved between the two species (93.6%). By in situ hybridization histochemistry, the expression of DAP kinase mRNA was observed in the mantle and ventricular zones of the entire neuraxis on embryonic day 15. However, the overall expression in the brain decreased markedly after birth and the expression was maintained at substantial levels in several restricted mature neuronal populations, such as olfactory bulb, hippocampal formation and cerebellar Purkinje and granule cells. Its wide expression during development and its maintained expression in the restricted mature neuronal population suggest that DAP kinase might be involved in some neuronal functions beyond simply executing the developmental neuronal cell death.     

Interstitial iodine-125 radiation without adjuvant therapy in the treatment of clinically localized prostate carcinoma

The electrophysiological properties of neurons of the medial septal nucleus and the nucleus of the diagnonal band of Broca (MS/DB) were studied using intracellular methods in urethane-anesthetized rats. Three types of rhythmically bursting neurons were identified in vivo on the basis of their action potential shapes and durations, afterhyperpolarizations (AHPs), membrane characteristics, firing rates and sensitivities to the action of muscarinic antagonist: (1) Cells with short-duration action potentials and no AHPs (2 of 34 rhythmic cells, 6%) had high firing rates and extremely reliable bursts with 6-16 spikes per theta cycle, which were highly resistant to scopolamine action. (2) Cells with short-duration action potentials and short-duration AHPs (8 of 34 rhythmic cells, 24%) also had high firing rates and reliable bursts with 4-13 spikes per theta cycle, phase-locked to the negative peak of the dentate theta wave. Hyperpolarizing current injection revealed a brief membrane time constant, time-dependent membrane rectification and a burst of firing at the break. Depolarizing current steps produced high-frequency repetitive trains of action potentials without spike frequency adaptation. The action potential and membrane and characteristics of this cell type are consistent with those described for GABAergic septal neurons. Many of these neurons retained their theta-bursting pattern in the presence of muscarinic antagonist. (3) Cells with long-duration action potentials and long-duration AHPs (24 of 34 rhythmic cells, 70%) had low firing rates, and usually only 1-3 spikes per theta cycle, locked mainly to the positive peak of the dentate theta rhythm. Hyperpolarizing current injection revealed a long membrane time constant and a break potential; a depolarizing pulse caused a train of action potentials with pronounced spike frequency adaptation. The action potential and membrane properties of this cell type are consistent with those reported for cholinergic septal neurons. The theta-related rhythmicity of this cell type was abolished by muscarinic antagonists. The phasic inhibition of "cholinergic" MS/DB neurons by "GABAergic" MS/DB neurons, followed by a rebound of their firing, is proposed as a mechanism contributing to recruitment of the whole MS/DB neuronal population into the synchronized rhythmic bursting pattern of activity that underlies the occurrence of the hippocampal theta rhythm.     

A multiple prognostic index predictive of disease outcome after irradiation for clinically localized prostate carcinoma

To reliably identify the residual tetracycline antibiotics (TCs), oxytetracycline (OTC), tetracycline, chlortetracycline (CTC) and doxycycline (DC), in bovine tissues, we have established a confirmation method using electrospray ionization liquid chromatography-tandem mass spectrometry (ESI LC-MS-MS) with daughter ion scan. All TCs gave [M+H-NH3]+ and [M+H-NH3-H2O]+ as the product ions, except for DC when [M+H]+ was selected as the precursor ion. The combination of C18 cartridge clean-up and the present ESI LC-MS-MS method can reliably identify TCs fortified at a concentration of 0.1 ppm in bovine tissues, including liver, kidney and muscle, and has been successfully applied to the identification of residual OTC in bovine liver and residual CTC in bovine muscle samples previously found at concentrations of 0.58 ppm and 0.38 ppm by LC, respectively.     

Results of radical prostatectomy in men with clinically localized prostate cancer

OBJECTIVE: To assess the results of radical prostatectomy in men with early prostate cancer. DESIGN: Retrospective, nonrandomized, multi-institutional pooled analysis. SETTING: Eight university medical centers in the United States and Europe. PATIENTS: A total of 2758 men with stage Tl and T2 prostatic cancer. MAIN OUTCOME MEASURES: Disease-specific and metastasis-free survival rates. RESULTS: Tumor grade was the most important preoperative factor in determining outcome. Disease-specific survival 10 years following surgery and associated 95% confidence intervals were 94% (range, 87%-98%), 80% (range, 74%-85%), and 77% (range, 65%-86%) for those men with grade 1, 2, and 3 tumors, respectively. Metastasis-free survival at 10 years was 87% (range, 78%-92%), 68% (range, 62%-73%), and 52% (range, 38%-64%) for patients with grade 1, 2, and 3 cancers, respectively. CONCLUSIONS: Radical prostatectomy leads to high 10-year disease-specific survival rates in men with all tumor grades. However, caution is needed in comparing these results with similar studies of alternative treatment strategies, such as watchful waiting, due to the inherent potential biases in uncontrolled trials. Nevertheless, these results offer the best currently available estimates of 10-year outcome of radical prostatectomy in men with clinically localized prostate cancer and may be useful in counseling patients with early malignancy.     

Analyzing outcome-based staging for clinically localized adenocarcinoma of the prostate

BACKGROUND: A clinical staging system based on the prostate-specific antigen (PSA) and the calculated prostate carcinoma volume (cVCa) construct previously has been proposed. This study was performed to assess whether this proposed clinical staging system was valid in an independent surgical and radiation data set in patients with clinically localized disease. METHODS: Cox regression multivariable analyses were used to assess the significance of staging systems (1992 American Joint Commission on Cancer Staging [AJCC] clinical and pathologic stage, versus cVCa-PSA clinical stage) to predict time to posttherapy PSA failure in 441 and 465 patients managed by surgery and radiation, respectively. Significant staging systems identified using Cox regression were tested further using established comparative measures to define the most clinically useful system. RESULTS: Both the 1992 AJCC pathologic stage and the cVCa-PSA clinical stage were significant predictors of time to postoperative PSA failure (P = 0.0001), whereas only the cVCa-PSA clinical stage was a significant predictor of time to postradiation PSA failure (P = 0.0001) using a Cox regression multivariable analysis. Further analyses using a pairwise comparison of the 1992 AJCC pathologic stage and cVCa-PSA clinical stage found the cVCa-PSA staging system provided a more clinically useful prediction of time to postoperative PSA failure. Specifically, the cVCa-PSA staging system was able to identify surgically managed patients with pathologic AJCC T2 disease who did poorly (3-year bNED = 22%) while also selecting patients with clinical AJCC T2b,c disease that was managed by radiation who did well (3-year bNED = 100%). CONCLUSIONS: A clinical staging system based on parameters obtained during the routine evaluation for AJCC clinical T1,2 prostate carcinoma provided a clinically useful stratification of both postoperative and postradiation PSA failure free survival.     

Outcome based staging for clinically localized adenocarcinoma of the prostate

PURPOSE: Some patients with clinically localized prostate cancer are not cured after radical prostatectomy because of the presence of occult systemic disease. The American Joint Commission on Cancer staging classification for prostate cancer does not reliably distinguish between clinically localized patients who are likely or unlikely to be cured after local therapy. This project was undertaken to develop a staging system capable of predicting long-term outcome after radical prostatectomy on the basis of the clinical parameters obtained routinely during the standard workup for patients with adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 688 clinically localized prostate cancer patients managed with a radical retropubic prostatectomy for adenocarcinoma of the prostate between 1989 and 1996 was evaluated for clinical features predictive of time to prostate specific antigen (PSA) failure using a Cox regression multivariate analysis. A recently defined clinical factor called the calculated prostate cancer volume and its ability to predict time to PSA failure in conjunction with PSA, biopsy Gleason score and clinical stage were evaluated. RESULTS: The calculated prostate cancer volume (p <0.0001) and the pretreatment PSA (p <0.001) provided the optimal staging system for predicting freedom from PSA failure after radical prostatectomy. CONCLUSIONS: The calculated prostate cancer volume and PSA may provide clinically useful information regarding outcome after radical prostatectomy, enabling the selection of a therapeutic approach for an individual patient with clinically localized disease. Validation of this staging system is needed.     

Radiotherapy for high grade clinically localized adenocarcinoma of the prostate

PURPOSE: We defined the efficacy of radiotherapy for the treatment of high grade (Gleason scores 8 to 10) adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 50 patients underwent radiotherapy with curative intent for clinically localized prostate cancer with Gleason scores of 8 to 10 at 1 of 4 facilities affiliated with the University of California San Francisco. Patients were considered to have biochemical failure if they had a significant increase in prostate specific antigen (PSA) of 0.5 ng./ml. per year, an increase in PSA to greater than 1.0 ng./ml. or a positive biopsy. RESULTS: Among the 50 patients median PSA was 22.7 ng./ml. (range 1.3 to 93.4). Tumors were clinical stage T1 or T2 in 46% of the cases and stage T3 or T4 in 54%. The overall actuarial probability of freedom from biochemical failure at 4 years was 23%. In a multivariate analysis including all patients pretreatment PSA was the only predictor of PSA failure, with 64% free of progression if the pretreatment PSA was 10 ng./ml. or less compared to only 16% at 3 years if PSA was more than 10 ng./ml. (p = 0.01). In a multivariate analysis restricted to patients with PSA less than 20 ng./ml. 83% of those treated to more than 71 Gy. were free of progression compared to 0% for those treated to less than 71 Gy. (p = 0.03). In a multivariate analysis PSA 10 ng./ml. or less (related risk 11.4, p = 0.02), T stage 1 or 2 (relative risk 3.8, p = 0.05) and radiation dose more than 71 Gy. (relative risk 4.0, p = 0.06) were associated with a favorable outcome. CONCLUSIONS: At 4 years the freedom from PSA failure following radiotherapy for high grade prostate cancer was comparable to previously reported surgical series. The high failure rate among patients with PSA greater than 20 ng./ml. suggests that these patients should be considered for investigational approaches. The apparent improvement in freedom from progression with the use of higher doses provides reason for optimism.     

Similar clinical outcomes in African-American and non-African-American males treated with suramin for metastatic prostate cancer

African-American males have a higher incidence of prostate cancer than non-African-American males and an overall poorer prognosis. Environmental factors such as socioeconomic status and biological factors such as an increased frequency of androgen receptor mutation have been identified as causal. As androgen ablation therapy is ubiquitous in the treatment of metastatic prostate cancer, little information is available on clinical outcome independent of hormone therapy. Our experience at the Warren G. Magnusson Clinical Center, National Institutes of Health with the anticancer agent, suramin, offers the opportunity to study clinical outcome in patients treated with an agent whose tumoricidal activity is not dependent on androgen receptor function. Clinical outcome was examined retrospectively in 43 patients treated on a single suramin-based protocol and evaluated as a function of ethnic background. No significant difference in time to disease progression or survival was observed between African Americans (n = 4) and the other 39 patients. These findings are consistent with the hypothesis that therapies that work through mechanisms independent of the androgen receptor may result in similar outcomes across ethnic groups.     

p53 nuclear protein expression is an independent prognostic marker in clinically localized prostate cancer patients undergoing radical prostatectomy

Immunohistochemical (IHC) staining for p53 protein nuclear expression was evaluated in archival paraffin-embedded radical prostatectomy specimens from 139 patients with clinically localized prostate cancer followed up from 1 to 8 (mean, 4) years. Elevated nuclear p53 protein expression was detected in 85 (61%) of 139 patients, being heterogeneous and focal in the majority of specimens. Only four specimens displayed homogeneous nuclear accumulation of p53 protein. Disease progression, most commonly prostate-specific antigen elevation, was noted in 46 (33%) patients, with 39 (85%) having positive p53 protein IHC stains. Conversely, 93 (67%) of 139 have not recurred, with 46 (49%) having positive p53. Of all 54 p53-negative patients, 47 (87%) have had no disease recurrence. An increased p53 protein IHC stain was associated with a higher pathological stage (T1 and T2, 51% versus >/=T3, 69%) and Gleason score 2-4, 17%; 5-7, 72%; and 8-10, 87.5%). Despite these associations, p53 IHC staining was an independent predictor of disease-free survival in a multivariate analysis of p53, age, race, stage, and grade. This study revealed that a majority of clinically localized prostate cancers heterogeneously express elevated nuclear levels of p53 protein in at least a subset of malignant cells, and that this expression is an independent predictor of disease progression in prostate cancer patients after radical prostatectomy.     

An evaluation of lymphography in localized carcinoma of the prostate

Lymph node biopsies were positive in 20% (7/35) of stage T1 and T2 (stage B) tumors and 64% (21/33) of stage T3 (stage C) tumors in 69 previously untreated and unselected patients with apparently localized carcinoma of the prostate. One patient with a To (stage A) tumor had no evidence of lymph node metastasis. Prospective analysis demonstrated an overall lymphographic accuracy of 78%, sensitivity of 57% and specificity of 92%. The detection of lymph node metastases in the lymphogram is limited by the frequency of microscopic metastasis and the frequency of benign changes within pelvic lymph nodes in this older patient population. Diagnostic criteria for metastatic disease which gives a low incidence of false-positive interpretations should be maintained, since relaxing the criteria will not necessarily improve the detection rate of metastases and would decrease specificity.     

Surgical therapy of locally confined prostate carcinoma

Since prostate specific antigen (PSA) has been established as marker for screening, a dramatic increase of prostatic cancer incidence has been observed over the past years. A further consequence of PSA-measurements lies in the observation that nowadays the majority of newly diagnosed prostatic carcinoma is in a clinically localized stage and therefore amendable to radical prostatectomy in a curative intervention. An important task yet to be solved is to find parameters able to estimate the malignant potential of the tumor preoperatively. Long-term results of radical prostatectomy are explained and the possibilities for reduction of intra- and perioperative complications are discussed.     

Cost benefit of emerging technology in localized carcinoma of the prostate

PURPOSE: In a health care environment strongly concerned with cost containment, cost-benefit studies of new technology must include analyses of loco-regional tumor control, morbidity, impact on quality of life, and financial considerations. METHODS AND MATERIALS: This nonrandomized study analyzes 124 patients treated with three-dimensional conformal radiation therapy (3D CRT) and 153 with standard irradiation (SRT) between January 1992 and December 1995, for histologically proven adenocarcinoma of prostate, clinical Stage T1 or T2. Mean follow-up is 1.4 years. Three-dimensional CRT consisted of six or seven coplanar oblique and lateral and, in some patients, AP fields designed to treat the prostate with a 1 to 1.7 cm margin. SRT consisted of 120 degrees bilateral arc rotation. Total doses to prostate were 67 to 70 Gy when pelvic lymph nodes were irradiated or 68.4 to 73.8 Gy when prostatic volume only was treated; dose per fraction was 1.8 Gy. Patients were interviewed weekly for severity of 12 acute intestinal and urinary pelvic irradiation side effects (0 to 4+ grading). Time and effort for 3D RTP and daily treatment with 3D CRT and SRT were recorded. Dose-volume histograms (DVHs) were calculated for gross tumor volume, planning target volume, bladder, and rectum. Actual reimbursement to the hospital and university was determined for 41 3D CRT, 43 SRT, and 40 radical prostatectomy patients treated during the same period. RESULTS: Average treatment planning times (in minutes) were: 101 for 3D conformal therapy simulation, 66 for contouring of target volume and sensitive structures, 55 for virtual simulation, 39 for plan preparation and documentation, 65 for physical simulation, and 20 for approval of treatment plan. Daily mean treatment times were 19 min for 3D CRT with Cerrobend blocking, 16 with multileaf collimation, and 10 with bilateral arc rotation. Dosimetric analysis (DVHs) showed a reduction of 50% in volume of bladder or rectum receiving doses higher than 65 Gy. Acute side effects included dysuria, moderate difficulty in urinating, and nocturia in 25-39% of both SRT and CRT patients; loose stools or diarrhea in 5-12% of 3D CRT and 16-22% of SRT patients; moderate proctitis in 3% of 3D CRT and 12% of SRT patients (p = 0.01). Chemical disease-free survival (prostate-specific antigen < or =2 ng/ml) at 3 years was 90% with 3D CRT and 80% with SRT (p = 0.01). Average initial treatment reimbursements were $13,823 (3D CRT), $10,864 (SRT), and $12,250 (radical prostatectomy). Average total treatment reimbursement and projected cost of management of initial therapy failures per patients were $15,173, $16,264, and $16,405, respectively. CONCLUSIONS: Three-dimensional CRT irradiated less bladder and rectum volume than SRT; CRT initial reimbursement was 28% higher than SRT and 12% higher than radical prostatectomy. Because of projected better local tumor control, average total cost of treating a patient with 3D CRT or radical prostatectomy is equivalent to cost of SRT. Treatment morbidity was lower with 3D CRT. Our findings reflect an overall benefit with 3D CRT as a new promising technology in treatment of localized prostate cancer. Dose-escalation studies may enhance its efficacy and cost benefit.     

DNA ploidy and survival of patients with clinically localized prostate cancer treated without intent to cure

We prospectively measured quantitative changes in the crystalline lens after trabeculectomy with mitomycin C. Twenty-four eyes in 24 trabeculectomy cases were consecutively enrolled in the study. The enrollment criteria consisted of: phakic eye, no history of intraocular surgeries and no corneal opacification. The transparency of the lens was measured and analyzed by EAS-1000 preoperatively, then 1 and 3 months postoperatively. Changes occurred primarily in the anterior part of the lens, especially in the anterior subcapsular region. The multivariate regression analysis demonstrated an association of cataract development with age, myopic refraction, difference in preoperative and postoperative IOP and systemic hypertension.     

Is there a role for cryoablation of the prostate in the management of localized prostate carcinoma?

It is impossible to adequately answer the question of whether there is a role for CSAP in the management of localized prostate carcinoma without considering the relative advantages and limitations of using other therapies to manage this disease (radical prostatectomy, radiation therapy, hormonal therapy, brachytherapy, expectant observation, and so on). Obviously, this is beyond the scope of this article. It is probably fair to point out, however, that the management of localized prostate carcinoma in the United States is generally quite controversial at the present time, and that despite a considerable amount of data pertaining to these therapeutic alternatives, it is difficult to discern a standard approach that can be broadly applied for all men with this disease. Therefore, if an absence of consensus on the management of localized prostate carcinoma does exist, it seems evident that investigations into alternative therapies are justified, and the preliminary results and efforts investigating CSAP fall well into this paradigm. In this context, several points can be made based on the available information. Significant numbers of patients who undergo CSAP can sustain undetectable levels of PSA for durable periods of time (more than 24 months). Thus, on a clinical level it seems possible to ablate the entire prostate with percutaneous CSAP, although rates of achieving this may be lower than originally anticipated. The reasons for persistence of carcinoma post CSAP are likely technical and related to the difficulties in determining the effective probe placements, number of probes to be used, number of freeze-thaw-freeze cycles to be used, and so on. Previous radiation exposure appears to confer an increased risk of CSAP-related morbidity, with incontinence, tissue sloughing, and rectal injury most prominent. Among nonradiated patients, incontinence is rare, and the most prominent postoperative concern involves BOO/tissue sloughing in a minority of patients. The longest follow-up data available on CSAP suggests that for patients with nonmetastatic prostate carcinoma, CSAP is associated with persistence of carcinoma in only 25% of patients. This compares favorably with the available biopsy data following external beam radiotherapy, in which most reports document positive biopsy results ranging between 30% and 100%, with the majority in the 40% to 50% range. Notably, the positive biopsy rate among patients with stage T3 disease following CSAP at 2 years can be less than 30%, which compares very favorably with previously reported positive biopsy result for these patients following external beam radiation therapy, which ranged between 40% and 100%. The management of patients with persistent carcinoma following CSAP poses fewer concerns to physicians than for those with persistent carcinoma following radiation therapy. Given the number of patients with prostate carcinoma who currently undergo radiotherapy as primary management, these data indicate that CSAP can now be considered a very viable therapeutic alternative for selected patients. With standardizations of technique as well as improved modifications in equipment, these preliminary CSAP results may well improve steadily in the near future. In the absence of randomized, comparative trials, it is difficult to draw meaningful comparisons between CSAP and radical prostatectomy. Based on available information, CSAP appears to be associated with a much lower incidence of stress and total incontinence than is radical prostatectomy. The rates of impotence following CSAP are somewhat comparable to those seen after radical prostatectomy, with wide variation among individual series. For patients who would be ideal candidates for radical prostatectomy (for example, less than stage T2c disease, PSA less than 10 ng/mL, and Gleason score of 7 or less), several authors have noted that the positive biopsy rate between 6 and 12 months is less than 10%.     

Endorectal coil magnetic resonance imaging identifies locally advanced prostate cancer in select patients with clinically localized disease

PURPOSE: The chemical and thermal stability of five species of mammalian serum albumins (human, bovine, dog, rabbit, and rat) were investigated, and conformational stabilities were compared to obtain structural information about the different albumins. METHODS: The chemical stability was estimated by using guanidine hydrochloride (GdnCl), and monitored by fluorometry and circular dichroism (CD). Thermal stability was evaluated by differential scanning calorimetry (DSC). RESULTS: In human, bovine, and rat albumin, two transitions were observed when GdnCl-induced denaturation was monitored fluorometrically, indicating at least one stable intermediate, although, in dog and rabbit albumin, only one transition was observed. However, GdnCl denaturation, as monitored by the ellipticity, showed a two-state transition in all species used in this study. Since these proteins, showing two transitions, contained a conserved tryptophan residue within domain II, these structural changes might have occurred in domain II during intermediate formation. DSC measurements showed that human, bovine, and rat albumin exhibited single sharp endotherms and these were clearly consistent with a two-state transition, while the deconvolution analysis of broad thermograms observed for dog and rabbit albumin showed that the absorption peaks could be approximated by a two-component composition, and were consistent with independent transitions of two different cooperative blocks. CONCLUSIONS: These experimental results demonstrate that species differences exist with respect to the conformational stability and the mechanism of the unfolding pathway for mammalian albumin.     

A nationwide survey of practicing urologists: current management of benign prostatic hyperplasia and clinically localized prostate cancer

PURPOSE: Our aim was to define the spectrum of urological care for benign prostatic hyperplasia (BPH) and clinically localized prostate cancer. MATERIALS AND METHODS: In 1995 a random sample of 394 American urologists was surveyed with a response rate of 67%. RESULTS: Respondents reported seeing a median of 240 BPH patients during the preceding 12 months, and they had prescribed alpha-blockers for 70 and finasteride for 15. They had performed a median of 25 transurethral prostatectomies but few other operations for BPH. Almost all urologists routinely used digital rectal examinations and prostate specific antigen tests for BPH diagnosis. The next most common studies were American Urological Association symptom scores and uroflowmetry. Pressure-flow studies were rarely done. Respondents reported seeing a median of 35 new patients with prostate cancer during the last year, and performing a median of 90 prostate biopsies and 13 radical prostatectomies. Respondents had referred a median of 10 patients for external beam radiotherapy but few patients received brachytherapy or cryotherapy. Urologist staging practices varied considerably. CONCLUSIONS: These data provide a picture of current practice regarding the management of BPH and prostate cancer.     

Population-based study of pelvic lymph node positivity in clinically localized prostate cancer: a study comparing African Americans and whites

Host genetic factors including major histocompatibility complex (MHC) polymorphisms influence both susceptibility to leprosy per se and also to leprosy type. Non-MHC genes may play an important role, but such genes remain undefined. The influence of two non-MHC candidate genes was assessed in a case-control study of Bengali leprosy patients from Calcutta. Recent studies have implicated variation in the vitamin D receptor (VDR) gene in susceptibility to several diseases, including osteoporosis and pulmonary tuberculosis. In this population, homozygotes for the alternate alleles of the VDR polymorphism are associated, respectively, with lepromatous and tuberculoid leprosy. The NRAMP1 (natural resistance associated macrophage protein 1) gene may influence human mycobacterial disease susceptibility based on studies with the murine homologue Nramp1. However, no significant association was found between NRAMP1 and leprosy susceptibility. This study suggests that the VDR polymorphism may influence susceptibility to some diseases by affecting the type and the strength of the host immune response.     

Physical activity in urban white, African-American, and Mexican-American women

PURPOSE AND METHODS: The purpose of this study was to analyze physical activity in a large, diverse sample of urban women (N = 521; X = 40.5 +/- 10.5 yr) relative to race/ethnicity, income, age, and education, using a sex-specific physical activity questionnaire. We also examined demographic and behavioral predictors of high levels (> or = 2000 kcal.wk-1) of leisure-time physical activity (LTPA; exercise, sports, recreational activities) in this population. RESULTS: The majority of women were sedentary (0-666 kcal.wk-1 in LTPA), and only 8% of African-American women (N = 6), 11% of Mexican-American women (N = 4), and 13% of white women (N = 55) participated in the level of physical activity recommended by the surgeon general (i.e., moderate to vigorous physical activity most days of the week for at least 30 min). Women of color, women over 40, and women without a college education had the lowest levels of participation in LTPA. Logistic regression analysis indicated that education was the only significant predictor of high LTPA in white women (P < 0.01) and marital status was the only significant predictor of high LTPA in minority women (P < 0.001). Age, body mass index (BMI; kg.m-2), income, self-rated health, alcohol intake, and smoking were not significant predictors of high LTPA for any of the women. Because the majority of adult women from this sample do not participate in adequate amounts of physical activity as recommended by the surgeon general, they may be at increased risk for hypokinetic diseases. CONCLUSIONS: These results indicate that public health efforts to increase physical activity in women should be focused on women of color, women over 40, and women without a college degree. More attention to predictors of physical activity that are specific to race or ethnicity may improve intervention program design and implementation.     

Systematic sextant biopsies improve preoperative prediction of pelvic lymph node metastases in patients with clinically localized prostatic carcinoma

PURPOSE: An algorithm including the results of systematic sextant biopsies was statistically developed and evaluated to predict the probability of pelvic lymph node metastases in patients with clinically localized carcinoma of the prostate. MATERIALS AND METHODS: Clinical stage, serum prostate specific antigen concentration, Gleason score, number of positive biopsies, number of biopsies containing any Gleason grade 4 or 5 cancer and number of biopsies predominated by Gleason grade 4 or 5 cancer were recorded in 345 patients undergoing pelvic lymph node dissection and correlated with the incidence of lymph node metastases. Multivariate logistic regression, and classification and regression trees analyses were performed. RESULTS: In univariate analysis all variables had a statistically significant influence on lymph node status. Logistic regression showed that the amount and distribution of undifferentiated Gleason grade 4 and 5 cancer in the biopsies were the best predictors of lymphatic spread followed by serum prostate specific antigen. Classification and regression trees analysis classified 79.9% of patients who had 3 or fewer biopsies with Gleason grade 4 or 5 cancer and no biopsies predominated by undifferentiated cancer as a low risk group. In this group positive lymph nodes occurred in only 2.2% (95% confidence interval 0.8 to 4.7%). CONCLUSIONS: Including the results of systematic sextant biopsies substantially enhances the predictive accuracy of algorithms that define the probability of lymph node metastases in prostatic cancer. Patients thus defined as having no lymphatic spread could potentially be spared pelvic lymph node dissection before definitive local treatment.