Time to onset of clinically meaningful improvement with tadalafil 5 mg once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: analysis of data pooled from 4 pivotal, double-blind, placebo controlled studies.

PURPOSE: Tadalafil once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia consistently shows statistically significant I-PSS improvements. However, physicians and patients wish to know whether tadalafil provides rapid, clinically meaningful improvement in lower urinary tract symptoms. In this post hoc analysis we integrated results from 4 placebo controlled studies to determine the duration of tadalafil once daily required to achieve clinically meaningful improvement. MATERIALS AND METHODS: We performed post hoc analysis of data integrated from 4 double-blind studies of tadalafil 5 mg and placebo once daily in 742 and 735 men, respectively, 45 years old or older with total I-PSS 13 or greater. Two clinically meaningful improvement categories were assessed, including 1) 3-point or greater baseline to end point total I-PSS improvement and 2) 25% or greater baseline to end point total I-PSS improvement. I-PSS was assessed at weeks 4, 8 and 12 in all studies, week 1 in 2 and week 2 in 1. Results in men treated with tadalafil who showed clinically meaningful improvement (responders) were further examined to determine the earliest time to clinically meaningful improvement. RESULTS: Of 742 tadalafil treated patients 513 (69.1%) and 444 (59.8%) demonstrated category 1 and 2 clinically meaningful improvement, respectively, at the study end point. Of 234 category 1 responders with week 1 assessments 140 (59.8%) achieved clinically meaningful improvement by week 1 and 407 of the total of 513 category 1 responders (79.3%) showed it by week 4. Of the 205 category 2 responders with week 1 assessments 103 (50.2%) achieved clinically meaningful improvement by week 1 while 322 of the 444 category 2 responders (72.5%) did so by week 4. CONCLUSIONS: Tadalafil 5 mg once daily led to clinically meaningful improvement in approximately two-thirds of men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. More than half of this group of tadalafil treated responders achieved clinically meaningful improvement after 1 week of therapy and more than 70% did so within 4 weeks.

Safety and efficacy of epelsiban in the treatment of men with premature ejaculation: a randomized, double-blind, placebo-controlled, fixed-dose study.

AIM: To assess the efficacy and safety of the selective oxytocin receptor antagonist epelsiban in the treatment of premature ejaculation (PE). METHODS: Double-blind, randomized, parallel-group, placebo-controlled, stopwatch-monitored, phase 2, multicenter study (GSK557296; NCT01021553) conducted in men (N=77) 18-55 years of age, with PE defined as per International Society for Sexual Medicine consensus definition. Patients provided informed consent prior to a 4-week un-medicated run-in to determine baseline intravaginal ejaculatory latency times (IELT) recorded in an electronic diary. Patients needed to make a minimum of four intercourse attempts and have a mean IELT<65 seconds to be considered for randomization. Men with moderate-to-severe erectile dysfunction were excluded from the study. Eligible patients were randomized to placebo, epelsiban 50 mg, or 150 mg, taken 1 hour before sexual activity. Active treatment IELT times were recorded in an electronic diary, along with subjective measures of intercourse satisfaction, over an 8-week treatment period. The Modified Index of Premature Ejaculation and International Index of Erectile Function were completed at study visits. MAIN OUTCOME MEASURES: Stopwatch timed IELT recordings and a modified version of the patient-reported outcome questionnaire the IPE were used in this study to determine the effect of epelsiban when taken orally prior to intercourse in subjects diagnosed with PE. RESULTS: The baseline (mean) IELT for patients pretreatment was (0.52, 0.63, and 0.59 minutes) for placebo, epelsiban 50 mg and 150 mg, respectively. On-treatment, average geometric least squares means of the median IELT values (mean) were slightly higher in the 50 mg and 150 mg groups (0.72 and 0.69 minutes), respectively, vs. the placebo group (0.62 minutes). Headache was the most common adverse event, and rates were similar across all groups. CONCLUSIONS: Epelsiban 50 mg and 150 mg were well tolerated, but did not result in a clinically or statistically significant change in IELT in men with PE, compared with placebo.

Prostate size does not predict high grade cancer.

PURPOSE: Several radical prostatectomy series have linked small prostates with high grade cancer based on the hypothesis that a small prostate results from a low androgen milieu that selects for less hormone dependent, more aggressive tumors. We previously reported that this association resulted from ascertainment bias from the performance characteristics of prostate specific antigen rather than from tumor biology in our radical prostatectomy cohort. In this study we analyzed this association in a more generalized population of men who underwent prostate needle biopsy. MATERIALS AND METHODS: The prostate needle biopsy database at our institution was queried for all initial biopsies. Included patient characteristics were age, race, family history of prostate cancer, prostate specific antigen, abnormal digital rectal examination and prostate volume in ml on transrectal ultrasound. Multivariate logistic regression was used to determine the influence of prostate volume on the odds of high grade cancer. RESULTS: The study population included 1,295 patients during 2000 to 2010, of whom 582 (44.9%) had prostate cancer and 398 (30.7%) had high grade cancer. When all patients were pooled, the OR for high grade cancer was 0.85 (95% CI 0.78-0.92) for each 10 ml increase in prostate volume. When patients were divided by clinical T stage, the corresponding ORs for those with T1c disease was 0.83 (95% CI 0.74-0.93) and for those with T2 or greater disease it was 0.99 (0.98-1.00). CONCLUSIONS: The association between small prostates and high grade cancer exists only in men with clinical T1c (normal digital rectal examination) prostate cancer. It likely resulted from ascertainment bias due to the performance characteristics of prostate specific antigen rather than tumor biology.

Estimating the risk of cancer associated with imaging related radiation during surveillance for stage I testicular cancer using computerized tomography.

PURPOSE: Computerized tomography has a critical role in the surveillance of stage I nonseminomatous germ cell tumors of the testis. Some protocols call for up to 16 computerized tomography scans over 5 years, thereby exposing young patients to a significant amount of radiation. We estimated the lifetime risk of cancer incidence and cancer death from imaging related radiation received during surveillance of stage I nonseminomatous germ cell tumor. MATERIALS AND METHODS: Using a model with a 64-slice computerized tomography scanner obtaining images of the abdomen and pelvis with or without chest in a standardized, phantom male patient, organ specific radiation doses were estimated using Monte Carlo simulation techniques. Lifetime attributable risks of cancer were estimated using the approach outlined in the Biological Effects of Ionizing Radiation VII Phase 2 report. RESULTS: With a 5-year surveillance protocol as suggested by the National Comprehensive Cancer Network, lifetime cancer risk ranged from 1 in 52 (1.9%) for an 18-year-old to 1 in 63 for a 40-year-old patient (1.2%). If chest computerized tomography is also performed the risk increases to 1 in 39 (2.6%) and 1 in 85 (1.6%), respectively. Lung and colon cancer accounted for most of the risk. The relative risk of a secondary malignancy with surveillance compared to a single scan after retroperitoneal lymph node dissection is approximately 15.2. CONCLUSIONS: Computerized tomography used in testicular cancer surveillance protocols imparts large radiation doses and is associated with a significant risk of cancer. This risk should be factored into counseling patients with stage I nonseminomatous germ cell tumor.

Decreasing use of luteinizing hormone-releasing hormone agonists in the United States is Independent of Reimbursement Changes: A Medicare and Veterans Health Administration claims analysis.

PURPOSE: Luteinizing hormone-releasing hormone agonists are the most common form of androgen deprivation therapy in men with prostate cancer. Limited data exist regarding physician decision-making in prescribing luteinizing hormone-releasing hormone agonists. We present an analysis of luteinizing hormone-releasing hormone agonist use trends based on a time matched comparison of data from Medicare and the Veterans Health Administration, a health care system unaffected by recent changes in Medicare reimbursement implemented by the Medicare Modernization Act in 2004. MATERIALS AND METHODS: Medicare claims and payment data were obtained from the Centers for Medicare and Medicaid Services from 2003 to 2007 for luteinizing hormone-releasing hormone agonists and for simple orchiectomy. The Veterans Health Administration Pharmacy Benefits Management database was queried for the annual number of prescriptions for luteinizing hormone-releasing hormone agonists during the same period. RESULTS: After implementation of the Medicare Prescription Drug, Improvement and Modernization Act in 2004 the reimbursement of luteinizing hormone-releasing hormone agonists in the Medicare population decreased by 54.8% and annual claims decreased by 25.1% from 2004 to 2007. During the same period luteinizing hormone-releasing hormone agonist use decreased by 16.8% in the Veterans Health Administration population. There was no compensatory increase in the use of simple orchiectomy for androgen deprivation therapy during the study period. CONCLUSIONS: Use of luteinizing hormone-releasing hormone agonists has decreased in the Medicare and Veterans Health Administration populations since 2004 without a compensatory increase in the use of alternative forms of androgen deprivation therapy. The shift in practice patterns is likely due to a decrease in Medicare reimbursement for these drugs, an increase in the use of intermittent therapy and increased recognition of the adverse effects associated with androgen deprivation therapy.

Crowdsourced Assessment of Ureteroscopy with Laser Lithotripsy Video Feed Does Not Correlate with Trainee Experience.

OBJECTIVES: We sought to validate the use of crowdsourced surgical video assessment in the evaluation of urology residents performing flexible ureteroscopic laser lithotripsy. METHODS: We collected video feeds from 30 intrarenal ureteroscopic laser lithotripsy cases where residents, postgraduate year (PGY) two through six, handled the ureteroscope. The video feeds were annotated to represent overall performance and to contain parts of the procedure being scored. Videos were submitted to a commercially available surgical video evaluation platform (Crowd-Sourced Assessment of Technical Skills). We used a validated ureteroscopic laser lithotripsy global assessment tool that was modified to include only those domains that could be evaluated on the captured video. Videos were evaluated by crowd workers recruited using Amazon's Mechanical Turk platform as well as five endourology-trained experts. Mean scores were calculated and intraclass correlation coefficients (ICCs) were computed for the expert domain and total scores. ICCs were estimated using a linear mixed-effects model. Spearman rank correlation coefficients were calculated as a measure of the strength of the relationships between the crowd mean and expert average scores. RESULTS: A total of 30 videos were reviewed 2488 times by 487 crowd workers and five expert endourologists. ICCs between expert raters were all below accepted levels of correlation (0.30), with the overall score having an ICC of <0.001. For individual domains, the crowd scores did not correlate with expert scores, except for the stone retrieval domain (0.60 p = 0.015). In addition, crowdsourced scores had a negative correlation with the PGY level (0.44, p = 0.019). CONCLUSIONS: There is poor agreement between experts and poor correlation between expert and crowd scores when evaluating video feeds of ureteroscopic laser lithotripsy. The use of an intraoperative video of ureteroscopy with laser lithotripsy for assessment of resident trainee skills does not appear reliable. This is further supported by the lack of correlation between crowd scores and advancing PGY level.

Racial variations in the performance of prostate specific antigen and prostate specific antigen density in the era of extended prostate biopsy schemes.

PURPOSE: The incidence of prostate cancer is known to vary as a function of race. To date few studies have evaluated the performance of the prostate specific antigen test and its indexes in unique racial populations. We examined the performance of prostate specific antigen, prostate specific antigen density and transition zone density in racial groups undergoing an extended prostate biopsy scheme. MATERIALS AND METHODS: A retrospective review was performed of prospectively collected data on 1,115 white, 288 black and 161 Asian/Pacific Islander men referred for prostate needle biopsy. All participants had not undergone previous biopsy. ROC curves stratified by race were ascertained for prostate specific antigen, prostate specific antigen density and transition zone density for detecting cancer and high grade cancer (Gleason 3 + 4 or greater). RESULTS: Across all races prostate specific antigen density outperformed prostate specific antigen for detecting any prostate cancer and high grade cancer. Prostate specific antigen and prostate specific antigen density performed best for diagnosing high grade cancer and diagnosing cancer in men with an abnormal digital rectal examination. When comparing differing races, prostate specific antigen density performed the best in Asian/Pacific Islander men for high grade cancer detection. The performance of transition zone density was inferior to that of prostate specific antigen density. CONCLUSIONS: Racial variations exist in the performance of prostate specific antigen and prostate specific antigen density. In men of Asian/Pacific Islander descent prostate specific antigen and prostate specific antigen density perform better than in white men, especially for diagnosing clinically significant, high grade prostate cancer. In general prostate specific antigen and prostate specific antigen density perform equally well in white and black populations.

The performance of prostate specific antigen, prostate specific antigen density and transition zone density in the era of extended biopsy schemes.

PURPOSE: Prostate specific antigen, prostate specific antigen density and transition zone density have been previously identified as prostate cancer detection tools. Recent studies suggest that prostate specific antigen may be increasingly accurate for detecting clinically significant high grade prostate cancer (Gleason grade 7 or greater). We defined the performance of these measures in a referral based population undergoing an extended prostate biopsy scheme. MATERIALS AND METHODS: We retrospectively reviewed prospectively collected data on 1,708 men referred for prostate needle biopsy. All participants were men who had not undergone biopsy in the past. From these data ROC curves were constructed for prostate specific antigen, prostate specific antigen density and transition zone density for the presence of cancer, high grade (Gleason 3 + 4 or greater) and high volume (50% or greater of cores positive) disease. RESULTS: Prostate specific antigen density had a statistically higher AUC than prostate specific antigen for detecting all prostate cancers (0.737 vs 0.633, p <0.001) as well as high grade (0.766 vs 0.673, p <0.001) and high volume (0.843 vs 0.755, p <0.001) disease. Additionally, prostate specific antigen and prostate specific antigen density performed better for detecting high grade and high volume disease compared to overall prostate cancer detection. The performance of transition zone density was similar to that of prostate specific antigen density. CONCLUSIONS: Prostate specific antigen and prostate specific antigen density show improved performance characteristics for detecting clinically significant high grade and high volume prostate cancer in referral populations undergoing extended scheme prostate needle biopsy. Prostate specific antigen density shows better performance characteristics than prostate specific antigen. No advantage was seen when using transition zone density over prostate specific antigen density.

Preclinical Testing of a Combination Stone Basket and Ureteral Balloon to Extract Ureteral Stones.

We have developed the Peralta Stone Extraction System to increase the safety of ureteral stone extraction. The device combines a nitinol stone basket and low-pressure balloon into a single device. After visualization, the stone is captured in the tipless nitinol basket and enveloped by a low-pressure balloon. We tested the performance of device prototypes in a porcine model using stone mimics with diameters ranging from 4.2 to 6.2 mm. Stones extracted with the device required less force when compared with stones in a standard ureteral stone basket. The force reduction was most pronounced for stones greater than 4.2 mm in diameter, and when traversing a ureteral stenosis model. In conclusion, a combination stone basket and balloon device may provide a new and safer way to extract ureteral stones.

Molecular activity of 1,25-dihydroxyvitamin D3 in primary cultures of human prostatic epithelial cells revealed by cDNA microarray analysis.

1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] exerts anti-proliferative, differentiating and apoptotic effects on prostatic cells. These activities, in addition to epidemiologic findings that link Vitamin D to prostate cancer risk, support the use of 1,25(OH)(2)D(3) for prevention or therapy of prostate cancer. The molecular mechanisms by which 1,25(OH)(2)D(3) exerts antitumor effects on prostatic cells are not well-defined. In addition, there is heterogeneity among the responses of various prostate cell lines and primary cultures to 1,25(OH)(2)D(3) with regard to growth inhibition, differentiation and apoptosis. To understand the basis of these differential responses and to develop a better model of Vitamin D action in the prostate, we performed cDNA microarray analyses of primary cultures of normal and malignant human prostatic epithelial cells, treated with 50 nM of 1,25(OH)(2)D(3) for 6 and 24 h. CYP24 (25-hydroxyvitamin D(3)-24-hydroxylase) was the most highly upregulated gene. Significant and early upregulation of dual specificity phosphatase 10 (DUSP10), validated in five additional primary cultures, points to inhibition of members of the mitogen-activated protein kinase (MAPK) superfamily as a key event mediating activity of 1,25(OH)(2)D(3) in prostatic epithelial cells. The functions of other regulated genes suggest protection by 1,25(OH)(2)D(3) from oxidative stress. Overall, these results provide new insights into the molecular basis of antitumor activities of Vitamin D in prostate cells.

The accordion antiretropulsive device improves stone-free rates during ureteroscopic laser lithotripsy.

PURPOSE: The Accordion is a novel endoscopic device that prevents retropulsion of ureteral stones and their fragments during ureteroscopic laser lithotripsy. We describe our experience with its use focusing on three main endpoints: operating time, fluoroscopy time, and stone-free rates. METHODS: Of 308 consecutive cases of unilateral ureteroscopic laser lithotripsy from 2006-2010, we analyzed 235 cases of ureteral stones. Chart review was performed to document patient demographics (age, sex, and race), stone characteristics (stone size, density, laterality, location, and multiplicity), operative characteristics (use of preoperative and/or postoperative stents, ureteral balloon dilators, ureteral access sheaths, the Holmium laser, and the Accordion device), and surgical outcomes (operative time, fluoroscopy time, stone-free status, and complications). RESULTS: The baseline characteristics between the Accordion and non-Accordion group were statistically similar. In univariate nonparametric tests of medians, Accordion device usage was not associated with a significant reduction in fluoroscopy time (median 1.68 vs. 1.95 minutes, p=0.28) or operating time (median 52.5 vs. 61 minutes, p=0.19). However, the stone-free rate for the Accordion group was significantly higher compared to the non-Accordion group (84.2% vs. 53.6%, p=0.001). In multivariate generalized linear models, Accordion usage was not associated with decreased operating or fluoroscopy times. Accordion use was associated with statistically significant greater odds of stone-free status (odds ratio 4.35, 95% confidence interval 2.36-8.00). Complication severity and rates were comparable between the two groups. CONCLUSIONS: The Accordion antiretropulsive device improves stone-free rates during ureteroscopic laser lithotripsy. Prospective studies are needed to validate these results.

Tracking intraoperative fluoroscopy utilization reduces radiation exposure during ureteroscopy.

PURPOSE: Recent studies have demonstrated deleterious effects of ionizing radiation from diagnostic and therapeutic imaging procedures. One of the barriers to minimizing patient exposure is physician awareness. We prospectively studied whether providing surgeons with feedback on their fluoroscopy utilization would affect intraoperative fluoroscopy times. MATERIALS AND METHODS: In 2007, we prospectively began to track fluoroscopy usage for all urology cases. Nine months later, surgeons started to receive periodic reports with their mean fluoroscopy time compared with their peers. We reviewed all ureteroscopic cases for nephrolithiasis from the date tracking began (2006-2010, n = 311). Using the initial 9-month period as a control, we studied the effect of providing feedback on mean fluoroscopy times in subsequent periods and analyzed patient factors that may affect radiation exposure. RESULTS: Mean fluoroscopy times for unilateral ureteroscopy decreased by 24% after surgeons received feedback (2.74-2.08 minutes, p = 0.002). On multivariate analysis, factors that independently predicted decreased fluoroscopy times included female sex (p = 0.02), stones in the distal ureter (p = 0.04), and if the surgeon had received feedback (p = 0.0004). Factors that increased fluoroscopy times included the presence of hydronephrosis (p = 0.001), use of a ureteral access sheath (p = 0.04), ureteral balloon dilation (p = 0.0001), and placement of a postoperative stent (p = 0.002). CONCLUSIONS: Providing surgeons with feedback on their fluoroscopy usage reduces patient and surgeon radiation exposure. Implementing such a tracking system requires minimal changes to existing operating room staff workflow. Further study is warranted to study the impact of this program on other procedures that utilize fluoroscopy in urology and other specialties.

Comparison of holding strength of suture anchors on human renal capsule.

INTRODUCTION: The use of surgical clips as suture anchors has made laparoscopic partial nephrectomy (LPN) technically simpler by eliminating the need for intracorporeal knot tying. However, the holding strength of these clips has not been analyzed in the human kidney. Therefore, the safety of utilizing suture anchors is unknown as the potential for clip slippage or renal capsular tears during LPN could result in postoperative complications including hemorrhage and urinoma formation. With the above in mind, we sought to compare the ability of Lapra-Ty clips and Hem-o-lok clips to function as suture anchors on human renal capsule. METHODS: Fresh human cadaveric kidneys with intact renal capsules were obtained. A Lapra-Ty clip (Ethicon, Cincinnati, OH) or a Hem-o-lok clip (Weck, Raleigh, NC) was secured to a no. 1 Vicryl suture (Ethicon) with and without a knot, as is typically utilized during the performance of LPN. The suture was then placed through the renal capsule and parenchyma and attached to an Imada Mechanical Force Tester (Imada, Northbrook, IL). The amount of force required both to violate the renal capsule and to dislodge the clip was recorded separately. RESULTS: Six Lapra-Ty clips and six Hem-o-lok clips were tested. The mean force in newtons required to violate the renal capsule for the Lapra-Ty group was 7.33 N and for the Hem-o-lok group was 22.08 N (p < 0.001). The mean force required to dislodge the clip from the suture for the Lapra-Ty group was 9.0 N and for the Hem-o-lok group was 3.4 N (p < 0.001). When two Hem-o-lok clips were placed on the suture in series, the mean force required to dislodge the clips was 10.6 N. CONCLUSION: When compared with Lapra-Ty clips, using two Hem-o-lok clips may provide a more secure and cost-effective method to anchor sutures on human renal capsule when performing LPN.

The influence of prostate volume on prostate-specific antigen performance: implications for the prostate cancer prevention trial outcomes.

PURPOSE: Although showing a 25% reduction in the biopsy prevalence of cancer compared with placebo in the Prostate Cancer Prevention Trial, finasteride was associated with a higher prevalence of high-grade disease. This observation was driven by "for-cause" biopsies. We sought to understand how volume-dependent changes in prostate-specific antigen test performance characteristics may have contributed. EXPERIMENTAL DESIGN: A retrospective review was done on 1,304 men referred for initial biopsy with a prostate-specific antigen between 4 and 10 ng/mL or an abnormal digital rectal examination. Receiver-operator curves and positive predictive values were ascertained for prostate-specific antigen stratified by diagnosis and prostate volume. RESULTS: The performance of prostate-specific antigen changed for any and high-grade (Gleason, > or =3 + 4) cancer in a volume-specific manner. For any cancer, the area under the curve (AUC) decreased from 0.758 to 0.629 to 0.520 as prostate volume increased (<30, 30-50, >50 cm(3), respectively). For high-grade cancer, a similar trend was shown (AUC, 0.712, 0.639, and 0.497, respectively). The positive predictive value of a prostate-specific antigen of > or =4 ng/mL was also affected by prostate volume. Trends for Gleason < or = 6 decreased as prostate volume increased (positive predictive value for <30 cm(3), 25.0%; positive predictive value for 30-50 cm(3), 23.8%; and positive predictive value for >50 cm(3), 17.3%). A more significant trend was seen for high-grade cancer (positive predictive value for <30 cm(3), 39.0%; positive predictive value for 30-50 cm(3), 22.3%; and positive predictive value for >50 cm(3), 10.7%). CONCLUSION: Decreases in prostate volume over time and the resultant change in prostate-specific antigen performance characteristics may have contributed a bias toward the detection of high-grade disease in the finasteride arm of the Prostate Cancer Prevention Trial.

Biochemical recurrence without PSA progression characterizes a subset of patients after radical prostatectomy. Prostate-specific antigen.

OBJECTIVES: To characterize a subset of patients with biochemical recurrence after radical prostatectomy but with little, if any, subsequent rise in serum prostate-specific antigen (PSA) and no clinical progression during long-term follow-up. METHODS: Of a series of 600 patients, 158 with biochemical recurrence after radical prostatectomy were examined. We identified a subset with measurable serum PSA levels during long-term follow-up, but with very low PSA velocity and no clinical recurrence. Serum PSA was measured with the ultrasensitive TOSOH assay with a PSA recurrence defined as a serum PSA of 0.07 ng/mL or greater. RESULTS: We identified 14 patients (8.8% of biochemical recurrences) with a detectable serum PSA level after radical prostatectomy yet without clinical or PSA progression at a mean follow-up after radical prostatectomy of 10.3 years. The mean time to PSA recurrence was 5.8 years, and the mean PSA velocity after recurrence was 0.028 ng/mL/yr. No clinical or pathologic features were found that could be used to identify this subset of patients. CONCLUSIONS: A subset of patients with biochemical recurrence after radical prostatectomy will not exhibit a progressive rise in serum PSA or clinical progression at 10 years follow-up. This suggests that serum PSA kinetics should be observed after biochemical recurrence before adjuvant hormonal therapy or radiotherapy.

Cavoatrial tumor thrombus excision without circulatory arrest.

INTRODUCTION: Traditional methods of cavoatrial thrombus excision use deep hypothermic circulatory arrest with significant associated morbidity and mortality. We describe a novel technique that avoids circulatory arrest, yet provides a bloodless field for tumor excision. TECHNICAL CONSIDERATIONS: A 59-year-old woman presented with a left renal mass and tumor thrombus with extension into the right atrium. After left radical nephrectomy, an aortic occlusion balloon was placed in the abdominal aorta at the level of the diaphragm, limiting flow in the inferior vena cava for tumor excision and maintaining both cerebral and spinal cord perfusion during cardiopulmonary bypass. Tumor excision was successfully performed using this technique with minimal postoperative morbidity in the patient described. She remained free of recurrence at 9 months of follow-up. CONCLUSIONS: Cavoatrial tumor thrombus excision can be successfully performed without deep hypothermic circulatory arrest.

Analysis of vitamin D-regulated gene expression in LNCaP human prostate cancer cells using cDNA microarrays.

BACKGROUND: 1,25-dihydroxyvitamin D(3) [1,25(OH)2D3] exerts growth inhibitory, pro-differentiating, and pro-apoptotic effects on prostate cells. To better understand the molecular mechanisms underlying these actions, we employed cDNA microarrays to study 1,25(OH)2D3-regulated gene expression in the LNCaP human prostate cancer cells. METHODS: mRNA isolated from LNCaP cells treated with vehicle or 50 nM 1,25(OH)2D3 for various lengths of time were hybridized to microarrays carrying approximately 23,000 genes. Some of the putative target genes revealed by the microarray analysis were verified by real-time PCR assays. RESULTS: 1,25(OH)2D3 most substantially increased the expression of the insulin-like growth factor binding protein-3 (IGFBP-3) gene. Our analysis also revealed several novel 1,25(OH)2D3-responsive genes. Interestingly, some of the key genes regulated by 1,25(OH)2D3 are also androgen-responsive genes. 1,25(OH)2D3 also down-regulated genes that mediate androgen catabolism. CONCLUSIONS: The putative 1,25(OH)2D3 target genes appear to be involved in a variety of cellular functions including growth regulation, differentiation, membrane transport, cell-cell and cell-matrix interactions, DNA repair, and inhibition of metastasis. The up-regulation of IGFBP-3 gene has been shown to be crucial in 1,25(OH)2D3-mediated inhibition of LNCaP cell growth. 1,25(OH)2D3 regulation of androgen-responsive genes as well as genes involved in androgen catabolism suggests that there are interactions between 1,25(OH)2D3 and androgen signaling pathways in LNCaP cells. Further studies on the role of these genes and others in mediating the anti-cancer effects of 1,25(OH)2D3 may lead to better approaches to the prevention and treatment of prostate cancer.

Gene expression patterns in renal cell carcinoma assessed by complementary DNA microarray.

Renal cell carcinoma comprises several histological types with different clinical behavior. Accurate pathological characterization is important in the clinical management of these tumors. We describe gene expression profiles in 41 renal tumors determined by using DNA microarrays containing 22,648 unique cDNAs representing 17,083 different UniGene Clusters, including 7230 characterized human genes. Differences in the patterns of gene expression among the different tumor types were readily apparent; hierarchical cluster analysis of the tumor samples segregated histologically distinct tumor types solely based on their gene expression patterns. Conventional renal cell carcinomas with clear cells showed a highly distinctive pattern of gene expression. Papillary carcinomas formed a tightly clustered group, as did tumors arising from the distal nephron and the normal kidney samples. Surprisingly, conventional renal cell carcinomas with granular cytoplasm were heterogeneous, and did not resemble any of the conventional carcinomas with clear cytoplasm in their pattern of gene expression. Characterization of renal cell carcinomas based on gene expression patterns provides a revised classification of these tumors and has the potential to supply significant biological and clinical insights.