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Abstract: Thirteen male and five female patients received a Conserve Plus hip resurfacing and prospectively provided blood samples to measure cobalt and chromium levels for up to 11 years. Trends in metal levels over time in unilateral and bilateral patients were studied. A multi-variate regression model was used to account for potential covariates. For unilaterals over all time intervals, the median Serum Cobalt level (CoS) was 1.06 μg/L, while the median Serum Chromium level (CrS) was 1.58 μg/L. For bilaterals, the median post operative CoS was 2.80 μg/L, while the median CrS was 5.80 μg/L. Metal levels increased within the first year then decreased and stabilized. These results show that serum metal levels in well-functioning implants can be low and do not increase with time. [Copyright &y& Elsevier]

Objective: We examined whether the depiction of brown adipose tissue (BAT) with positron emission tomography/computed tomography (PET/CT) in pediatric patients is associated with anthropometric meaures. Study design: We determined measures of body mass, adiposity, and musculature in 71 children and adolescents who underwent PET/CT examinations and compared patients with and without BAT. We used regression analyses to assess the relation between BAT and anthropometric measures. Results: A total of 30 patients (42%) had BAT depicted on PET/CT, 10 of 26 girls (38%) and 20 of 45 boys (44%). Compared with patients without functional BAT, patients with BAT had significantly greater neck musculature (1880 ± 908 cm3 versus 1299 ± 806 cm3; P = .028 for boys and 1295 ± 586 cm3 versus 854 ± 392 cm3; P = .030 for girls) and gluteus musculature (1359 ± 373 cm3 versus 1061 ± 500 cm3; P = .032 for boys and 1138 ± 425 cm3 versus 827 ± 297 cm3; P = .038 for girls), but no differences in age, body mass index, or measures of subcutaneous fat. With logistic regression analyses, neck and pelvic musculature predicted the presence of BAT independently of age, sex, body size, and season of scan (P = .018 and .009, respectively). Conclusion: Pediatric patients with visualized BAT on PET/CT examinations had significantly greater muscle volume than patients with no visualized BAT. [ABSTRACT FROM AUTHOR]

Abstract: There are limited data to guide surgeon recommendations regarding activities after total joint arthroplasty. The present study aims to better clarify the current community standards. A questionnaire was distributed to the members of the American Association for Hip and Knee Surgeons attending the 2007 annual meeting inquiring about recommendations for 15 activities for patients with total hip arthroplasty or total knee arthroplasty. One hundred thirty-nine surveys were returned. Spearman rank correlation was used to analyze the data. More than 95% of the responses placed no limitations on low-impact activities including level surface walking, stair climbing, level surface bicycling, swimming, and golf. Higher-impact activities were more commonly discouraged, although there was considerable variability. Recommendations after total hip arthroplasty were more liberal compared to those after total knee arthroplasty. Higher-volume surgeons tended to be more liberal in their recommendations. No responder indicated that there was strong scientific evidence for their recommendations. Investigations are needed to elucidate the long-term effects of higher load and/or higher cycle activities on total joint arthroplasty. [Copyright &y& Elsevier]

Objective: To study the refractory cases of Kawasaki disease (KD) and identify potential risk factors in patients in whom standard therapy fails. Study design: A retrospective chart review of patients with KD admitted from January 1, 2002, through December 31, 2006. Demographic, clinical, laboratory, echocardiographic, and therapeutic data were recorded. Results: Of 196 patients, 40 (20%) needed re-treatment. The number of refractory cases were 7 (14.3%), 6 (17.1%), 11(28.9%), 10 (24.4%), and 6 (17.6%) for 2002 to 2006, respectively. There were no significant differences in age, sex, ethnicity, number of days with symptoms at diagnosis, white blood cell count, erythrocyte sedimentation rate (ESR), or C-reactive protein (CRP). Refractory patients had higher band counts (22.7% vs 7%), lower albumin levels (3 vs 3.4), and a higher number of abnormal echocardiography results at diagnosis (80% vs 16.1%). Conclusions: An elevated band count, low albumin level, and an abnormal initial echocardiography result can be useful tools to identify patients at risk for a more complicated clinical course. [Copyright &y& Elsevier]

Abstract: Patients who are treated with steroids for immunosuppression after solid organ transplant are at risk for development of osteonecrosis. The purpose of this study was to determine the prevalence of symptomatic osteonecrosis of the hip and knee in patients who were treated with corticosteroids after cardiac transplantation and to determine if there was a relationship between steroid dose and the development of osteonecrosis. We retrospectively evaluated 204 patients who underwent cardiac transplantation and noted that only 6 (3%) of 204 patients developed symptomatic osteonecrosis of the hip or knee. The osteonecrosis was diagnosed an average of 38.5 months (range, 21-52 months) after transplantation. There was no association noted between steroid dose and the development of symptomatic osteonecrosis. The low prevalence of osteonecrosis supports the hypothesis that the development of osteonecrosis in these patients is an idiosyncratic response to steroids, perhaps related to an underlying hypercoagulable state or hypofibrinolysis. [Copyright &y& Elsevier]

Abstract: The purpose of the present study was to determine the effectiveness of modifications in the surgical technique on loosening of the femoral component in the first 600 consecutive Conserve Plus metal-on-metal hybrid resurfacings (Wright Medical Technologies, Arlington, Tenn). These modifications were gradually introduced over time, but all the changes were implemented after the first 300 hips. The average age of the patients was 48.9 years, and 74% were male. The average follow-up was 70.5 months for the first 300 hips and 42.4 months for the second 300, and there was a significant improvement (P = .016) of the second 300 hips over the first 300 in a time-dependant analysis using as an end point the time to appearance of a radiolucency, suggesting potential femoral component loosening. None of the components with cemented stems showed femoral radiolucencies or were revised for aseptic loosening. Adding fixation holes in the dome and chamfered areas and cleansing and drying using a suction tip in the dome hole were significantly related to the improvement of the results. Positioning the femoral component in a more valgus position did not show any effect as an independent variable. [Copyright &y& Elsevier]

Purpose: The purpose of this study was to quantify the stiffness of the human finger proximal interphalangeal (PIP) joint and to study its relationship to different common clinical parameters. Methods: Eighty-nine normal adult subjects had their PIP joints of the index, middle, and ring fingers evaluated using a computer-controlled moment-angle plotter. This device was used to measure stiffness and energy absorbed at the PIP joint during passive flexion and extension. Results: The average overall stiffness was 0.05 N-cm/degree. There was a weak correlation between stiffness and energy absorbed and the size of the finger: they both increased with the size of the finger. The men’s fingers were stiffer and absorbed more energy than the corresponding women’s fingers. No significant associations were found between the time of day when the test took place, occupation, hobbies, or age with stiffness or absorbed energy. No significant differences were associated with hand dominance. The finger on the dominant hand had a larger circumference for both genders. Heavier individuals had more stiffness and absorbed more energy than lighter individuals. Conclusions: The PIP joint stiffness was defined quantitatively and measured over a wide cross-section of a normal population. This may allow future studies to record the outcome of different treatments for finger joint stiffness objectively. The stiffness was greater in men and in larger fingers. [Copyright &y& Elsevier]

Objectives: To examine risk factors for fracture in a racially diverse cohort of healthy children in the US. Study design: A total of 1470 healthy children, aged 6-17 years, underwent yearly evaluations of height, weight, body mass index, skeletal age, sexual maturation, calcium intake, physical activity levels, and dual-energy x-ray absorptiometry (DXA) bone and fat measurements for up to 6 years. Fracture information was obtained at each annual visit, and risk factors for fracture were examined using the time-dependent Cox proportional hazards model. Results: The overall fracture incidence was 0.034 fracture per person-year with 212 children reporting a total of 257 fractures. Being white (hazard ratio [HR] = 2.1), being male (HR = 1.8), and having skeletal age of 10-14 years (HR = 2.2) were the strongest risk factors for fracture (all P ≤ .001). Increased sports participation (HR = 1.4), lower body fat percentage (HR = 0.97), and previous fracture in white girls (HR = 2.1) were also significant risk factors (all P ≤ .04). Overall, fracture risk decreased with higher DXA z scores, except in white boys, who had increased fracture risk with higher DXA z scores (HR = 1.7, P < .001). Conclusions: Boys and girls of European descent had double the fracture risk of children from other backgrounds, suggesting that the genetic predisposition to fractures seen in elderly adults also manifests in children. [ABSTRACT FROM AUTHOR]

Objective: To examine whether anthropometric measurements, blood pressure (BP), fasting total cholesterol, and low-density lipoprotein are related to ultrasound measures of carotid intima-media thickness (CIMT) in children and teenagers with no known risk factors for cardiovascular disease. Study design: This cross-sectional study included 599 subjects, 6 to 20 years of age (292 males, 307 females; 224 Hispanics, 210 European-Americans, 126 African-Americans, and 39 Asian-Americans) whose body mass index, waist circumference, BP, lipid profiles, and values for CIMT were determined. Results: Measures of CIMT were significantly greater in males than females (P =.006) and in African-Americans when compared with other ethnic groups (all P < .05). There were no relations between age, diastolic BP, or fasting levels of triglycerides, total cholesterol, or low-density lipoprotein values and CIMT measures, regardless of sex or ethnic background. Stratified multiple regression analysis indicated that body mass index and waist circumference independently predicted CIMT in both males and females, even after controlling for age, weight, BP, fasting lipid levels, and ethnic background. Conclusion: Increased body mass and adiposity are associated with increased intima-media thickness in children and teenagers. This association is present in children not considered overweight, underscoring the need for the continued promotion of adequate nutritional and physical exercise behavior during childhood. [Copyright &y& Elsevier]

Abstract: Objectives: To compare tissue androgen levels in the prostate gland of African-American and white men, looking for a possible explanation of the increased incidence of cancer in the former. Methods: The subjects were 25 African-American and 36 white men, undergoing prostate biopsy consecutively, in whom cancer was absent. Biopsy cores (18 gauge) from the peripheral zone were homogenized, subjected to ether extraction, and separation by chromatography. Tissue testosterone and dihydrotestosterone (DHT) levels were determined by radioimmunoassay. Results: The groups were matched for mean age (67.6 ± 9.6 years), prostate volume (37.9 ± 21.0 cm3), body mass index (28.2 ± 4.2 kg/m2), and serum prostate-specific antigen (2.8 to 3.4 ng/mL) and testosterone (330 ± 114 ng/dL) levels (P = NS for all measures). No significant difference in tissue testosterone (median 0.8 ng/g) or DHT (median 4.6 ng/g) was found between groups (P = NS). Furthermore, the tissue DHT/testosterone ratio (∼5) was not significantly different between the two groups (P = NS). Conclusions: Prostatic tissue levels of testosterone and DHT were similar in African-American and white men; thus, the present data do not support a hypothesis of increased androgenic activity in African-American men. Because the ratio of DHT/testosterone in prostatic tissue was similar in the two groups, the possibility of increased 5-alpha-reductase activity in African-American men did not seem likely. Using needle biopsy specimens, both absolute values and the ratio of the androgens in prostatic tissue were similar to those found in previous studies using surgically excised glands. Thus, quick-frozen biopsy cores appear to be a valuable tissue source for evaluating the androgen status within the prostate. [Copyright &y& Elsevier]

Cytokines associated with osteolysis have been demonstrated in tissues surrounding failed metal–metal (MM) total hip replacements (THRs). The objective of the present study was to semi-quantify the amounts of inflammatory cytokines in tissues from 28 failed MM THRs, and determine their relationship with the quantity of metal particles. Paraffin sections were immunohistochemically stained with monoclonal antibodies: anti-IL-1-β, anti-IL-6 and anti-TNF-α. Cytokines and metal particles were rated in 10 fields per tissue using standard light microscopy. Because of the use of light microscopy, only relatively large particles or agglomerations of particles were visible. Therefore, a polarized light and a semi-quantitative scheme based on the discoloration of cell cytoplasms induced by the presence of particles were used to evaluate the quantity of metal particles. Results showed an overall higher amount of IL-6 than IL-1β while TNF-α remained at very low levels. For each patient, the average IL-1β and IL-6 ratings decreased when the average particle rating increased, following a linear regression, with relatively high correlation factors (r=−0.69 for IL-1β and r=−0.57 for IL-6). IL-1β decreased about twice as fast as IL-6. TNF-α, remaining at very low levels, did not demonstrate any correlation with particle rating. When multiple tissues were available for the same patient, the correlation factors between the average cytokine and particle ratings were highly variable between samples, demonstrating the heterogeneity between the tissues from the same patient. At the cellular level, there was an even higher correlation between the quantity of metal particles and the production of IL-1β and IL-6 (r=−0.99), while TNF-α did not demonstrate any correlation, remaining at very low levels. In conclusion, this study showed that tissues surrounding failed MM THRs with low to moderate quantities of metal particles can induce the production of potentially osteolytic cytokines. However, the overall number of cells producing these cytokines tended to be lower than that typically seen in tissues surrounding metal-polyethylene THRs. [Copyright &y& Elsevier]

: ObjectivesTo investigate the relationship between physician-assessed quality-of-life (QOL) parameters obtained from patient interview and patient self-report of QOL by using the short form of the Urogenital Distress Inventory (UDI-6).: MethodsFemale patients presenting for the first time at our clinic at two different academic institutions were consecutively evaluated. All patients were asked to fill out the UDI-6 while in the waiting area before their appointment. One additional global QOL question specific to the patient’s overall urinary condition was included in the questionnaire. A physician who was unaware of the patient’s responses then interviewed all patients. The physicians then filled out the UDI-6 on the basis of their impression of the patient’s symptoms from the patient’s responses during the medical interview. A statistician unaware of the patient’s diagnosis and presenting symptoms compared the physician and patient symptom bother assessments.: ResultsSeventy-nine patients were analyzed. Statistical analysis with weighted kappas revealed poor concordance between the physician and patient responses. Overall, the physicians at both institutions underestimated the patient’s degree of bother 25% to 37% of the time.: ConclusionsReports of outcomes after treatment of urinary incontinence should always include independent patient self-administered questionnaires. Because of interviewer bias, physician assessment of QOL tends to underestimate a patient’s bother from urinary symptoms. [Copyright &y& Elsevier]

: ObjectivesTo determine the ideal cutpoint for defining prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Although various cutpoints have been used, a recent study suggested that 0.4 ng/mL may be the most appropriate.: MethodsA retrospective survey of 358 men undergoing RP at the West Los Angeles Veterans Affairs Medical Center between 1991 and 2001 was undertaken. The 3-year and 5-year risk of PSA recurrence was estimated by Kaplan-Meier analyses using various cutpoints of postoperative PSA to define recurrence: greater than 0.1, greater than 0.2, greater than 0.3, greater than 0.4, and greater than 0.5 ng/mL. The 1 and 3-year risk of PSA progression after a detectable PSA level (PSA rising to a higher cutpoint) was evaluated for each definition of PSA recurrence using Kaplan-Meier analyses. Multivariate analysis using a Cox proportional hazards model was used to determine the clinical variables that were significant independent predictors of PSA recurrence at each cutpoint.: ResultsFor patients with a detectable postoperative PSA value from 0.11 to 0.2 ng/mL, the 1 and 3-year risk of PSA progression was 64% (95% confidence interval [CI] 46% to 82%) and 93% (95% CI 74% to 99%), respectively. For patients with a PSA value from 0.21 to 0.3 ng/mL, the 1 and 3-year risk of PSA progression was 86% (95% CI 69% to 97%) and 100% (95% CI 87% to 100%), respectively. The use of higher PSA cutpoints to define recurrence resulted in a lower 5-year risk of PSA recurrence. The 5-year risk of PSA recurrence using a greater than 0.1 ng/mL cutpoint resulted in a 43% (95% CI 36% to 50%) risk of recurrence compared with only 23% (95% CI 18% to 30%) for a greater than 0.5 ng/mL cutpoint. In multivariate analysis, PSA and biopsy Gleason score were significant independent predictors of biochemical recurrence, regardless of the definition of PSA recurrence used (P ≤0.002).: ConclusionsPSA and biopsy Gleason score were significant predictors of biochemical failure, regardless of the definition of failure used. However, the definition of PSA recurrence dramatically affected the perceived success of therapy. Patients with a postoperative PSA value greater than 0.2 ng/mL are at very high risk of developing an additional rise in PSA. On the basis of this finding, a PSA value greater than 0.2 ng/mL is an appropriate cutpoint to define PSA recurrence after RP. [Copyright &y& Elsevier]

Objectives: Whether race is an independent predictor of prostate-specific antigen (PSA) recurrence after RP is controversial. To compare racial differences in clinical and pathologic features and biochemical recurrence in men undergoing radical prostatectomy (RP), we used a newly established multicenter database of patients from four equal-access healthcare centers in California, the Shared Equal Access Regional Cancer Hospital (SEARCH) database.Methods: A retrospective survey of 1547 patients treated with RP at four different equal-access medical centers in California between 1988 and 2001 was undertaken. Race was categorized as white (n = 1014), black (n = 338), or nonwhite-nonblack (n = 195). Patients were analyzed for racial differences in preoperative variables (age at surgery, clinical stage, PSA, and biopsy Gleason score) and surgical variables (pathologic stage, surgical Gleason score, incidence of seminal vesicle invasion, positive surgical margins, capsular penetration, and pelvic lymph node involvement). Patients were followed up for PSA recurrence. Multivariate analysis was used to determine whether race was an independent predictor of biochemical failure.Results: Significant differences were found among the races in the preoperative factors of clinical stage, age, serum PSA, and biopsy Gleason score, although the absolute differences were small. No differences were found among the races in the pathologic features of the RP specimens, including Gleason score, pathologic stage, and incidence of positive surgical margins, capsular penetration, seminal vesicle invasion, or lymph node involvement. In both univariate and multivariate analyses, only serum PSA (P <0.001) and biopsy Gleason score (P <0.001) were significant independent predictors of time to biochemical recurrence.Conclusions: In a large multicenter cohort of patients from four equal-access medical care facilities in California, although racial differences were found in clinical stage, age, biopsy Gleason score, and serum PSA level at diagnosis, we found race was not an independent predictor of biochemical recurrence after RP. Race should not be used in models or nomograms predicting PSA failure after RP. The current study represents the largest series of black patients and the first large series of nonwhite-nonblack patients treated with RP reported to date. The Shared Equal Access Regional Cancer Hospital database is a valuable resource for studying patients treated with RP. [ABSTRACT FROM AUTHOR]

Objectives. The percentage of total prostate needle biopsy tissue with cancer was previously found to be a stronger predictor of biochemical failure after radical prostatectomy (RP) than either biopsy Gleason score or serum prostate-specific antigen (PSA). To improve our ability to predict preoperatively the risk of biochemical recurrence after RP, we sought to determine the cutpoints of the percentage of biopsy tissue with cancer to separate patients into low, intermediate, or high-risk groups. We then examined whether we could further stratify low, intermediate, and high-risk groups (on the basis of the PSA level and biopsy Gleason score) using the percentage of prostate needle biopsy tissue with cancer.Methods. A single pathologist reviewed the prostate needle biopsy specimens of 217 men who underwent RP between 1991 and 2001. Biopsy specimens were examined for Gleason score and the percentage of total biopsy tissue with cancer. Cutpoints were identified to define patients with differing risk of biochemical recurrence after RP. These cutpoints were applied to low, intermediate, and high-risk patients, on the basis of PSA and biopsy Gleason score, to determine whether preoperative risk stratification could be improved.Results. Using the cutpoints for the percentage of prostate needle biopsy tissue with cancer of less than 20% (low risk), 20% to less than 55% (intermediate risk), and 55% or greater (high risk), patients were separated into three groups with differing risks of biochemical failure after RP (hazard ratio 1.95, 95% confidence interval 1.37 to 2.77, P <0.001). These cutpoints further stratified patients with an intermediate (P = 0.002) or high risk (P = 0.05) of biochemical failure (on the basis of the PSA and biopsy Gleason score). However, these cutpoints provided no improvement in risk stratification for patients who were at low risk (P = 0.501) of biochemical failure (on the basis of PSA and biopsy Gleason score).Conclusions. The percentage of total prostate needle biopsy tissue with cancer can be used to stratify patients into low, intermediate, and high-risk groups preoperatively for biochemical recurrence after RP. These cutpoints could further stratify patients preoperatively who were at intermediate or high risk of biochemical failure on the basis of PSA and biopsy Gleason score. [Copyright &y& Elsevier]

Objectives Targeted biopsy, using magnetic resonance (MR)-ultrasound (US) fusion, may allow tracking of specific cancer sites in the prostate. We aimed to evaluate the initial use of the technique to follow tumor sites in men on active surveillance of prostate cancer. Methods and materials A total of 53 men with prostate cancer (all T1c category) underwent rebiopsy of 74 positive biopsy sites, which were tracked and targeted using the Artemis MR-US fusion device (Eigen, Grass Valley, CA) from March 2010 through January 2013. The initial biopsy included 12 cores from a standard template (mapped by software) and directed biopsies from regions of interest seen on MR imaging (MRI). In the repeat biopsy, samples were taken from sites containing cancer at the initial biopsy. Outcomes of interest at second MR-US biopsy included (a) presence of any cancer and (b) presence of clinically significant cancer. Results All cancers on initial biopsy had either Gleason score 3+3 = 6 ( n = 63) or 3+4 = 7 ( n = 11). At initial biopsy, 23 cancers were within an MRI target, and 51 were found on systematic biopsy. Cancer detection rate on repeat biopsy (29/74, 39%) was independent of Gleason score on initial biopsy ( P = not significant) but directly related to initial cancer core length ( P <0.02). Repeat sampling of cancerous sites within MRI targets was more likely to show cancer than resampling of tumorous systematic sites (61% vs. 29%, P = 0.005). When initial cancer core length was≥4 mm within an MRI target, more than 80% (5/6) of follow-up tracking biopsies were positive. An increase of Gleason score was uncommon (9/74, 12%). Conclusions Monitoring of specific prostate cancer–containing sites may be achieved in some men using an electronic tracking system. The chances of finding tumor on repeat specific-site sampling was directly related to the length of tumor in the initial biopsy core and presence of tumor within an MRI target; upgrading of Gleason score was uncommon. Further research is required to evaluate the potential utility of site-specific biopsy tracking for patients with prostate cancer on active surveillance. [ABSTRACT FROM AUTHOR]

Abstract: Background: Conventional biopsy fails to detect the presence of some prostate cancers (PCas). Men with a prior negative biopsy but persistently elevated prostate-specific antigen (PSA) pose a diagnostic dilemma, as some harbor elusive cancer. Objective: To determine whether use of magnetic resonance–ultrasound (MR-US) fusion biopsy results in improved detection of PCa compared to repeat conventional biopsy. Design, setting, and participants: In a consecutive-case series, 105 subjects with prior negative biopsy and elevated PSA values underwent multiparametric magnetic resonance imaging (MRI) and fusion biopsy in an outpatient setting. Intervention: Suspicious areas on multiparametric MRI were delineated and graded by a radiologist; MR–US fusion biopsy was performed by a urologist using the Artemis device; targeted and systematic biopsies were obtained regardless of MRI result. Outcome measurements and statistical analysis: Detection rates of all PCa and clinically significant PCa (Gleason ≥3+4 or Gleason 6 with maximal cancer core length ≥4mm) were determined. The yield of targeted biopsy was compared to systematic biopsy. The ability of an MRI grading system to predict clinically significant cancer was investigated. Stepwise multivariate logistic regression analysis was performed to determine predictors of significant cancer on biopsy. Results and limitations: Fusion biopsy revealed PCa in 36 of 105 men (34%; 95% confidence interval [CI], 25–45). Seventy-two percent of men with PCa had clinically significant disease; 21 of 23 men (91%) with PCa on targeted biopsy had significant cancer compared to 15 of 28 (54%) with systematic biopsy. Degree of suspicion on MRI was the most powerful predictor of significant cancer on multivariate analysis. Twelve of 14 (86%) subjects with a highly suspicious MRI target were diagnosed with clinically significant cancer. Conclusions: MR–US fusion biopsy provides improved detection of PCa in men with prior negative biopsies and elevated PSA values. Most cancers found were clinically significant. [Copyright &y& Elsevier]

Objective: Nonmyeloablative cytoreduction is used in clinical hematopoietic stem cell gene therapy trials to increase engraftment of gene-modified cells. We utilized an infant rhesus monkey model to identify an optimal dosage of busulfan that results in efficient long-term gene marking with minimal toxicities. Methods: Bone marrow (BM) was harvested, followed by a single 2-hour intravenous infusion of busulfan at escalating dosages of 0 to 160 mg/m2. CD34+ cells were immunoselected from BM, transduced overnight with a simian immunodeficiency virus–based lentiviral vector carrying a nonexpressed marker gene, and injected intravenously 48 hours post–busulfan administration. Pharmacokinetics were assessed, as well as adverse effects and peripheral blood and BM gene marking. Results: Increasing dosages of busulfan resulted in increased area-under-the-curve (AUC) with some variability at each dosage level, suggesting interindividual variation in clearance. Blood chemistries were normal and no adverse effects were observed as a result of busulfan infusion. At 120 and 160 mg/m2, transient neutropenia and thrombocytopenia were noted but not lymphopenia. Over the 6 months of study posttransplantation, a busulfan dosage-related increase in gene marking was observed ranging from undetectable (no busulfan) up to 0.1% gene-containing cells in animals achieving the highest busulfan AUC. This corresponds to a more than 100-fold increase in gene marking over the busulfan dosage range studied. Conclusions: These data indicate that increased gene marking of hematopoietic stem cells can be achieved by escalating busulfan dosages from 40 to 160 mg/m2 without significant toxicity in infant nonhuman primates. [Copyright &y& Elsevier]

Abstract: Objectives. To investigate the relationship between diet and prostate cancer (CaP) among native Japanese (NJ) and second-generation or third-generation Japanese-American (J-A) men—focusing on the effects of animal fat and soy on prostatic tissues. Methods: The subjects were 50 Japanese men undergoing radical prostatectomy, 25 NJ living in Nagoya, Japan and 25 U.S.-born J-A men, living in Los Angeles, California. A priori, the NJ men were believed to be a low-fat, high-soy group and the J-A men, a high-fat, low-soy group. The studies included postoperative measurements of diet (Block questionnaire), body fat (bioimpedance), blood, urine, and prostatic biomarkers in malignant and adjacent normal tissue, using a tissue microarray made from the original paraffin blocks. Results: The NJ and J-A men were similar in age (65 to 70 years old; P <0.05), prostate-specific antigen level (7.1 to 8.6 ng/mL), prostate volume (35 to 38 cm3), and Gleason score (5.6 to 6.6), but their body composition differed. J-A men had more body fat (24% versus 19%), higher serum triglyceride levels (245 versus 106 mg/dL), lower estradiol levels (27 versus 31 ng/mL), and much lower urinary soy-metabolite levels (1:3) than NJ men (P <0.02). In both NJ and J-A groups, expression of numerous tissue biomarkers separated normal from CaP tissue, including markers for apoptosis (Bcl-2, caspase-3), growth factor receptors (epidermal growth factor receptor), racemase, 5-lipoxygenase, kinase inhibition (p27), and cell proliferation (Ki-67; all P <0.02). Furthermore, within both normal and CaP tissues, caspase-3 and 5-lipoxygenase were expressed more in NJ than in J-A men (P <0.01). Nuclear morphometry showed that the chromatin in each of the four groups (normal versus CaP, NJ versus J-A) was different (area under the curve 85% to 94%, P <0.01), despite fundamental genetic homogeneity. Conclusions: NJ and J-A men, products of similar genetics but differing environments, were shown to have differences in body composition that could influence CaP evolution. The CaP specimens from the NJ and J-A men were histologically similar, but tissue biomarker expression, especially of lipoxygenase and the caspase family, suggested differing mechanisms of carcinogenesis. Differences in nuclear morphometry suggested the additional possibility of gene-nutrient interactions. [Copyright &y& Elsevier]

The purpose of the study was to evaluate unilocular and multilocular cystic renal cell carcinoma (cRCC). These tumors are a rare entity, comprising approximately 1 to 2% of all renal tumors, and their true biologic behavior is not well-known. Initial review of renal cell carcinoma (RCC) cases treated at our institution between 1989 and 2001 identified 39 cases of cRCC. However, histopathologic review of these cases by 2 pathologists revealed that only 18 cases met the criteria that all tumors have a cystic component that constitutes at least 75% of the total lesion without evidence of necrosis. These cases were compared to 614 conventional clear cell RCC cases with regards to clinical outcomes. All 18 patients presented with localized (N0M0) disease. Thirteen (72%) of the tumors were Fuhrman Grade 1, while the remaining 5 (28%) were Fuhrman Grade 2. By comparison, only 60% of the clear cell RCC tumors were Grade 1 or 2. Similarly, 83% of cRCC were pT1 tumors compared to only 35% of conventional clear cell tumors. Mean tumor size for the cRCC tumors was 4.9 cm compared to 7.4 cm for conventional clear cell tumors. Cystic RCC patients had an 82% four-year disease-specific survival (DSS). Unilocular and multilocular cRCC is a distinct subtype of clear cell RCC. Its biology appears to be more favorable with regards to important prognostic factors such as metastatic presentation, Fuhrman grade, 1997 T stage, and tumor size. These findings suggest that cRCC patients may benefit from nephron sparing surgery. [Copyright &y& Elsevier]

Objectives: To perform a retrospective analysis to determine the operative morbidity in patients with substantial comorbidities requiring renal surgery. Increasing numbers of patients requiring renal surgery are presenting with substantial comorbidities, such as diabetes mellitus, chronic obstructive pulmonary disease, and cardiovascular disease.Methods: The American Society of Anesthesiologists (ASA) physical status classification was used to define perioperative risk. Of 1087 patients who underwent nephrectomy between 1989 and 2001, 237 patients were classified as ASA classification 1 or 2 (low risk), 297 were ASA classification 3 (intermediate risk), and 17 were ASA classification 4 (high risk).Results: No statistically significant differences were found among the low-risk, intermediate-risk, or high-risk patients with regard to 1997 T stage distribution, mean tumor size, vascular and/or inferior vena cava involvement, percentage of partial nephrectomy, adjacent organ resection, or preoperative hemoglobin. Intermediate-risk patients did have a greater estimated blood loss (946 versus 739 mL, P = 0.05), leading to greater transfusion rates (42% versus 28%, P = 0.001). However, no increase occurred in intraoperative or postoperative morbidity. High-risk patients also had greater transfusion rates, as well as a greater rate of complications occurring more than 24 hours after surgery.Conclusions: Partial or radical nephrectomy can be offered to patients with comorbid conditions. ASA classification 3 patients are more likely to require transfusion. This may have been a result of a lower threshold to transfuse patients with preoperative morbidities. However, the perioperative and postoperative complication rates were similar to those of low-risk patients. Not surprisingly, high-risk patients had greater rates of transfusions and complications. [Copyright &y& Elsevier]

Objectives: To determine whether in the prostate-specific antigen (PSA) era stage and/or grade migration of patients treated with radical prostatectomy (RP) has occurred. We also examined whether the biochemical recurrence rates after RP have changed with time.Methods: A total of 1654 patients from the Shared Equal Access Regional Cancer Hospital (SEARCH) database were analyzed for time trends in age, preoperative PSA level, clinical stage, biopsy Gleason score, prostatectomy Gleason grade, pathologic stage, margin status, and recurrence rates after RP. Results were stratified into three 4-year blocks of time between 1988 and 2002 for analysis.Results: The preoperative PSA level, patient age, tumor stage, rate of capsular penetration, and lymph node involvement decreased with time. Both biopsy and pathologic Gleason grade steadily increased with time. The positive margin rate and incidence of seminal vesicle involvement remained stable. On multivariate analysis, only serum PSA level (P <0.001) and biopsy Gleason score (P <0.001) were significant independent predictors of the time to recurrence after RP. The year of surgery was not a significant independent predictor of biochemical recurrence after RP in multivariate analysis.Conclusions: Despite lower stage and lower PSA levels with time, we found no improvement in PSA recurrence rates over time. This may reflect lead-time bias in detecting PSA recurrence by the use of more sensitive PSA assays in recent years. [ABSTRACT FROM AUTHOR]

Objectives: Tumor volume in the prostate needle biopsy is an important prognosticator for patients with prostate cancer. However, the best method to measure tumor volume in the prostate needle biopsy is unknown. We compared the total percentage of biopsy tissue with cancer to the percentage of cores positive for their ability to predict adverse pathologic findings and biochemical failure after radical prostatectomy (RP).Methods: A retrospective survey of 355 patients from the Shared Equal Access Regional Cancer Hospital database treated with RP between 1990 and 2002 was undertaken. Multivariate analysis was used to compare the percentage of cores and percentage of tissue with cancer to the standard clinical variables of age, prostate-specific antigen (PSA) level, biopsy Gleason score, and clinical stage for their ability to predict positive surgical margins, non-organ-confined disease, seminal vesicle invasion, and time to PSA recurrence after RP.Results: On multivariate analysis, the percentage of tissue with cancer significantly predicted non-organ-confined disease and seminal vesicle invasion, but the percentage of cores did not significantly predict any of the pathologic features examined. In separate multivariate analysis, only the percentage of tissue with cancer, but not the percentage of cores with cancer, significantly predicted PSA failure. Moreover, when compared in the same multivariate analysis, only the percentage of tissue with cancer (hazard ratio 8.25, 95% confidence interval 3.06 to 22.22, P <0.001) was a significant predictor. The area under the receiver operating curves for predicting PSA failure was significantly greater for the percentage of tissue with cancer (0.697) than for the percentage of cores (0.644, P = 0.022). Cutpoints for the percentage of tissue with cancer (less than 20%, 20% to 40%, and greater than 40%) and the percentage of cores (less than 34%, 34% to 50%, greater than 50%) both provided significant preoperative risk stratification for biochemical failure, although the percentage of tissue with cancer cutpoints provided better risk stratification (higher hazard ratios and lower P value). Cutpoints for the percentage of tissue with cancer but not the percentage of cores positive further stratified patients who were at low (P = 0.041), intermediate (P = 0.002), and high (P = 0.023) risk on the basis of the PSA level and biopsy Gleason score.Conclusions: The percentage of tissue with cancer was better than the percentage of cores at predicting advanced pathologic features and PSA recurrence after RP. Unlike the percentage of cores, the percentage of tissue with cancer cutpoints further stratified low, intermediate, and high-risk patients on the basis of PSA level and biopsy Gleason score. Although the percentage of tissue with cancer is a slightly more cumbersome measurement than the percentage of positive cores, it provided statistically and clinically superior preoperative risk stratification for biochemical failure after RP. [ABSTRACT FROM AUTHOR]

: ObjectivesTo perform a retrospective study to determine whether survival and immunotherapy response are related to the site of metastases (lung versus bone) and to the number of organ sites involved (one versus multiple). The most common sites of metastatic renal cell carcinoma (mRCC) are the lung and bone.: MethodsThe records of 434 patients with mRCC were reviewed. Patients with pathologic evidence of nodal involvement were excluded, leaving 120 patients with mRCC to lung only, 33 patients to bone only, and 144 patients with multiple organ involvement. The response rates to immunotherapy and overall survival were compared. The variables evaluated in statistical analyses included Eastern Cooperative Oncology Group score, grade, 1997 tumor stage, and multiple organ involvement.: ResultsThe median survival for patients with lung only and bone only mRCC was 27 months; patients with multiple organ involvement had a median survival of 11 months. In patients who underwent nephrectomy followed by immunotherapy, the median survival time was 31, 31, and 13 months in the lung, bone, and multiple sites groups, respectively. The response rate to immunotherapy after nephrectomy was 44%, 20%, and 14% in the lung, bone, and multiple organ groups, respectively. Multivariate analysis confirmed that metastatic disease to more than one organ site was associated with poor prognosis (2.05 risk ratio, P <0.001).: ConclusionsPatients with mRCC to only one organ site fared significantly better than patients who had evidence of disease in multiple organs. Survival in patients with disease limited to the lung was similar to that of patients whose disease was limited to bone. [Copyright &y& Elsevier]