Atreya Dash

Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma of 4–7 cm

To compare the outcomes of patients who had a elective partial nephrectomy (PN) or radical nephrectomy (RN) for clear cell renal cell carcinoma (RCC) of 4–7 cm.

Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder

Perioperative cisplatin‐based chemotherapy has shown benefit in patients with high‐risk localized urothelial bladder cancer, but it is not widely used. Renal impairment may be a major factor limiting its use. The current study was designed to determine the proportion of patients ineligible to receive adjuvant cisplatin‐based chemotherapy based on inadequate renal function alone.

Changes in differential gene expression because of warm ischemia time of radical prostatectomy specimens.

The expression of thousands of genes can be monitored simultaneously using cDNA microarray technology. This technology is being used to understand the complexity of human disease. One significant technical concern regards potential alterations in gene expression because of the effect of tissue ischemia. This study evaluates the increase in the differential gene expression because of tissue processing time. To evaluate differential gene expression because of ischemia time, prostate samples were divided into five time points (0, 0.5, 1, 3, and 5 hours). Each time point consisted of a homogeneous mixture of 12 to 15 prostate tissue cubes (5 mm(3)). These tissues were maintained at room temperature until at the assigned time point the tissue was placed in OCT, flash frozen in liquid nitrogen, and stored at -80 degrees C until RNA extraction. RNA from each time point was hybridized against an aliquot of 0 time point RNA from the same prostate. Four prostate glands were used in parallel studies. M-A plots were graphed to compare variability between time point sample hybridizations. Statistical Analysis of Microarray software was used to identify genes overexpressed at the 1-hour time point versus the 0-hour time with statistically significance. Microarray analysis revealed only a small percentage of genes (<0.6%) from more than 9000 to demonstrate overexpression at the 1-hour time point. Among the 41 statistically significant named overexpressed genes at the 1-hour time point were early growth response 1 (EGR1), jun B proto-oncogene (jun B), jun D proto-oncogene (jun D), and activating transcription factor 3 (ATF3). Genes previously associated with prostate cancer did not have significantly altered expression with ischemia time. Increased EGR1 protein expression was confirmed by Western blot analysis. Microarray technology has opened the possibility of evaluating the expression of a multitude of genes simultaneously, however, the interpretation of this complex data needs to be assessed circumspectly using refined statistical methods. Because RNA expression represents the tissue response to insults such as ischemia, and is also sensitive to degradation, investigators need be mindful of confounding artifacts secondary to tissue processing. All attempts should be made to process tissue rapidly to ensure that the microarray gene profile accurately represents the state of the cells and confirmatory studies should be performed using alternative methods (eg, Northern blot analysis, Western blot, immunohistochemistry).

Prevalence and Significance of Fluoroquinolone Resistant Escherichia coli in Patients Undergoing Transrectal Ultrasound Guided Prostate Needle Biopsy

PURPOSE We estimated the prevalence of fluoroquinolone resistant Escherichia coli in patients undergoing repeat transrectal ultrasound guided prostate needle biopsy and identified high risk groups. MATERIALS AND METHODS From January 2009 to March 2010 rectal swabs of 136 men from 3 institutions undergoing transrectal ultrasound guided prostate needle biopsy were obtained. There were 33 men with no previous biopsy who served as the controls. Participants completed questionnaires and rectal swab culture was obtained just before performing the prostate biopsy. Selective media was used to specifically isolate fluoroquinolone resistant E. coli and sensitivities were obtained. The patients were contacted via telephone 7 days after the procedure for a followup questionnaire. RESULTS A total of 30 patients had cultures positive for fluoroquinolone resistant bacteria for an overall rate of 22% (95% CI 15, 29). Patients with diabetes and Asian ethnicity had higher risks of resistant rectal flora colonization (OR 2.3 and 2.8, respectively). However, differences did not reach statistical significance (p = 0.09 and p = 0.08, respectively). Patients with no prior biopsy had a positive rate of 15% (5 of 33) compared to 24% (25 of 103) in those with 1 or more prior biopsies (OR 1.8, p = 0.27). Five patients (3.6%) had post-biopsy fever while only 1 of those patients had a positive rectal swab. CONCLUSIONS Using selective media to isolate fluoroquinolone resistant E. coli from the rectum before transrectal ultrasound guided prostate biopsy, we isolated organisms in 22% of patients with a wide resistance pattern. This protocol may be used to provide information regarding targeted antibiotic prophylaxis before transrectal prostate biopsies.

Overtreatment of men with low-risk prostate cancer and significant comorbidity

Men with low‐risk prostate cancer and significant comorbidity are susceptible to overtreatment. The authors sought to compare the impact of comorbidity and age on treatment choice in men with low‐risk disease.

Integrative Analysis of Genomic Aberrations Associated with Prostate Cancer Progression

Integrative analysis of genomic aberrations in the context of trancriptomic alterations will lead to a more comprehensive perspective on prostate cancer progression. Genome-wide copy number changes were monitored using array comparative genomic hybridization of laser-capture microdissected prostate cancer samples spanning stages of prostate cancer progression, including precursor lesions, clinically localized disease, and metastatic disease. A total of 62 specific cell populations from 38 patients were profiled. Minimal common regions (MCR) of alterations were defined for each sample type, and metastatic samples displayed the most number of alterations. Clinically localized prostate cancer samples with high Gleason grade resembled metastatic samples with respect to the size of altered regions and number of affected genes. A total of 9 out of 13 MCRs in the putative precursor lesion, high-grade prostatic intraepithelial neoplasia (PIN), showed an overlap with prostate cancer cases (amplifications in 3q29, 5q31.3-q32, 6q27, and 8q24.3 and deletions in 6q22.31, 16p12.2, 17q21.2, and 17q21.31), whereas postatrophic hyperplasia (PAH) did not exhibit this overlap. Interestingly, prostate cancers that do not overexpress ETS family members (i.e., gene fusion-negative prostate cancers) harbor differential aberrations in 1q23, 6q16, 6q21, 10q23, and 10q24. Integrative analysis with matched mRNA profiles identified genetic alterations in several proposed candidate genes implicated in prostate cancer progression.

Molecular profiling of human prostate tissues: Insights into gene expression patterns of prostate development during puberty

Testosterone production surges during puberty and orchestrates massive growth and reorganization of the prostate gland, and this glandular architecture is maintained thereafter throughout adulthood. Benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCA) are common diseases in adulthood that do not develop in the absence of androgens. Our objective was to gain insight into gene expression changes of the prostate gland at puberty, a crucial juncture in prostate development that is androgen dependent. Understanding the role played by androgens in normal prostate development may provide greater insight into androgen involvement in prostatic diseases. Benign prostate tissues obtained from pubertal and adult age group cadaveric organ donors were harvested and profiled using 20,000 element cDNA microarrays. Statistical analysis of the microarray data identified 375 genes that were differentially expressed in pubertal prostates relative to adult prostates including genes such as Nkx3.1, TMEPAI, TGFBR3, FASN, ANKH, TGFBR2, FAAH, S100P, HoxB13, fibronectin, and TSC2 among others. Comparisons of pubertal and BPH expression profiles revealed a subset of genes that shared the expression pattern between the two groups. In addition, we observed that several genes from this list were previously demonstrated to be regulated by androgen and hence could also be potential in vivo targets of androgen action in the pubertal human prostate. Promoter searches revealed the presence of androgen response elements in a cohort of genes including tumor necrosis factor‐α induced adipose related protein, which was found to be induced by androgen. In summary, this is the first report that provides a comprehensive view of the molecular events that occur during puberty in the human prostate and provides a cohort of genes that could be potential in vivo targets of androgenic action during puberty.

Comorbidity and competing risks for mortality in men with prostate cancer

Accurate estimation of life expectancy is essential for men deciding between aggressive and conservative treatment of prostate cancer. The authors sought to assess the competing risks of nonprostate cancer and prostate cancer mortality among men with differing Charlson comorbidity index scores and tumor risks.

Ureteroscopic treatment of renal calculi in morbidly obese patients: A stone-matched comparison

OBJECTIVES To report a matched comparison of morbidly obese (MO) patients and normal weight (NW) patients who underwent ureteroscopic (URS) treatment of renal calculi. Shock wave lithotripsy and percutaneous nephrostolithotomy may be precluded in MO patients, and URS treatment offers a minimally invasive alternative. METHODS We retrospectively reviewed the charts of patients who underwent URS at our institution between 1997 and 2000. Fifty-four patients underwent URS treatment solely for renal calculi. Sixteen MO patients underwent 18 procedures. Thirty-eight NW patients, who underwent 39 procedures, were matched to the MO patients by stone location and size. Stones were categorized by location and size, less than 10 mm or 10 mm or greater. The factors and outcomes assessed were stone length, operative time, presence of a ureteral stent, success, and complications. RESULTS The overall success rate was 83% (15 of 18 procedures) for MO patients and 67% (26 of 39 procedures) for NW patients, but this difference was not significant (P = 0.23). The difference in the success rate for renal calculi 10 mm or greater (100% versus 38%) approached significance (P = 0.09). This may be related to other distinctions between the groups. URS treatment was often a salvage therapy in the NW group after other modalities failed. No significant differences were found between the other outcomes. CONCLUSIONS URS treatment of renal calculi when matched for location and size is as successful and no more morbid in MO than in NW patients. URS treatment of renal calculi is a safe and effective first-line treatment for renal calculi in MO patients.

The RAZOR (randomized open vs robotic cystectomy) trial: Study design and trial update

The purpose of the RAZOR (randomized open vs robotic cystectomy) study is to compare open radical cystectomy (ORC) vs robot‐assisted RC (RARC), pelvic lymph node dissection (PLND) and urinary diversion for oncological outcomes, complications and health‐related quality of life (HRQL) measures with a primary endpoint of 2‐year progression‐free survival (PFS). RAZOR is a multi‐institutional, randomized, non‐inferior, phase III trial that will enrol at least 320 patients with T1–T4, N0–N1, M0 bladder cancer with ≈160 patients in both the RARC and ORC arms at 15 participating institutions. Data will be collected prospectively at each institution for cancer outcomes, complications of surgery and HRQL measures, and then submitted to trial data management services Cancer Research and Biostatistics (CRAB) for final analyses. To date, 306 patients have been randomized and accrual to the RAZOR trial is expected to conclude in 2014. In this study, we report the RAZOR trial experimental design, objectives, data safety, and monitoring, and accrual update. The RAZOR trial is a landmark study in urological oncology, randomizing T1–T4, N0–N1, M0 patients with bladder cancer to ORC vs RARC, PLND and urinary diversion. RAZOR is a multi‐institutional, non‐inferiority trial evaluating cancer outcomes, surgical complications and HRQL measures of ORC vs RARC with a primary endpoint of 2‐year PFS. Full data from the RAZOR trial are not expected until 2016–2017.