Partial Nephrectomy is Associated with Higher Risk of Relapse Compared with Radical Nephrectomy for Clinical Stage T1 Renal Cell Carcinoma Pathologically Up Staged to T3a.

PURPOSE: We studied recurrence-free survival after partial vs radical nephrectomy for clinical stage T1 renal cell carcinoma in all patients and in those up staged to pathological stage T3a. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,250 patients who underwent partial or radical nephrectomy for clinically localized T1 renal cell carcinoma between 2006 and 2014. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of nephrectomy type with the log rank test and Cox models, adjusting for clinical, radiological and pathological characteristics. RESULTS: A total of 86 recurrences (7%) were observed during a median followup of 37 months. No difference in recurrence-free survival between partial and radical nephrectomy was found among all clinical stage T1 renal cell carcinomas. T3a up staging was noted in 140 patients (11%) and recurrent disease was observed in 44 (31.4%) during a median followup of 38 months. Among up staged T3a cases partial nephrectomy was associated with shorter recurrence-free survival compared to radical nephrectomy on univariable analysis (recurrence HR 2.04, 95% CI 1.12-3.68, p = 0.019) and multivariable analysis (recurrence HR 5.39, 95% CI 1.94-14.9, p = 0.001). CONCLUSIONS: In a subgroup of patients clinically staged T1 renal cell carcinoma will be pathologically up staged to T3a. Among these patients those who undergo partial nephrectomy appear to have inferior recurrence-free survival relative to those who undergo radical nephrectomy.

Active surveillance for incidental renal mass in the octogenarian.

OBJECTIVE: To evaluate the oncologic outcomes among a large cohort of octogenarian patients placed on active surveillance for a localized renal mass. METHODS: We retrospectively reviewed patients ≥80 years of age presenting for asymptomatic, incidentally detected clinically localized stage T1 renal mass between 2006 and 2013 who were followed by active surveillance (AS). The primary endpoint was development of metastatic renal cell carcinoma. Secondary outcomes included intervention-free survival, cancer-specific survival, and overall survival. RESULTS: Eighty-nine octogenarians (median age = 83.4 years) were placed on AS for a median 29.9 months. Median Charlson Comorbidity Index and Katz Index of Independence in Activities of Daily Living scores were 2 and 5, respectively. For all comers, median initial tumor size was 2.4 cm with median growth rate of 0.20 cm/year. Eight (9.0%) patients failed AS due to delayed intervention and three (1.1%) due to systemic progression after median follow-up of 27.8 and 39.9 months, respectively. Two (2.2%) patients in the delayed intervention cohort developed metastasis after treatment. Tumor growth rate was significantly higher among those undergoing intervention versus no intervention (0.60 vs. 0.15 cm/year, P = 0.05) and among patients with systemic progression versus no metastasis (1.28 vs. 0.18 cm/year, P = 0.001). Five-year intervention-free, metastasis-free, cancer-specific, and overall survivals were 90.6, 95.6, 95.6, and 85.7%, respectively. CONCLUSION: AS represents an effective management strategy in octogenarians given low overall risk of metastasis. Tumor growth kinetics may identify patients at risk of systemic progression in whom treatment should be considered.

Outcomes of Laparoscopic Partial Nephrectomy in Patients Continuing Aspirin Therapy.

PURPOSE: A clinical dilemma surrounds the use of aspirin therapy during laparoscopic partial nephrectomy. Despite reduced cardiac morbidity with perioperative aspirin use, fear of bleeding related complications often prompts discontinuation of therapy before surgery. We evaluate perioperative outcomes among patients continuing aspirin and those in whom treatment is stopped preoperatively. MATERIALS AND METHODS: A total of 430 consecutive cases of laparoscopic partial nephrectomy performed between January 2012 and October 2014 were reviewed. Patients on chronic aspirin therapy were stratified into on aspirin and off aspirin groups based on perioperative status of aspirin use. Primary end points evaluated included estimated intraoperative blood loss and incidence of bleeding related complications, major postoperative complications, and thromboembolic events. Secondary outcomes included operative time, transfusion rate, length of hospital stay, rehospitalization rate and surgical margin status. RESULTS: Among 101 (23.4%) patients on chronic aspirin therapy, antiplatelet treatment was continued in 17 (16.8%). Bleeding developed in 1 patient in the on aspirin group postoperatively and required angioembolization. Conversely 1 myocardial infarction was observed in the off aspirin cohort. There was no significant difference in the incidence of major postoperative complications, intraoperative blood loss, transfusion rate, length of hospital stay and rehospitalization rate. Operative time was increased with continued aspirin use (181 vs 136 minutes, p=0.01). CONCLUSIONS: Laparoscopic partial nephrectomy is safe and effective in patients on chronic antiplatelet therapy who require perioperative aspirin for cardioprotection. Larger, prospective studies are necessary to discern the true cardiovascular benefit derived from continued aspirin therapy as well as better characterize associated bleeding risk.

Positive Surgical Margins Increase Risk of Recurrence after Partial Nephrectomy for High Risk Renal Tumors.

PURPOSE: The clinical significance of a positive surgical margin after partial nephrectomy remains controversial. The association between positive margin and risk of disease recurrence in patients with clinically localized renal neoplasms undergoing partial nephrectomy was evaluated. MATERIALS AND METHODS: A retrospective multi-institutional review of 1,240 patients undergoing partial nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013 was performed. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of positive surgical margin with the log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (pT2-3a or Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups. RESULTS: A positive surgical margin was encountered in 97 (7.8%) patients. Recurrence developed in 69 (5.6%) patients during a median followup of 33 months, including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III-IV). A positive margin was associated with an increased risk of relapse on multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of recurrence. In a stratified analysis based on pathological features, a positive surgical margin was significantly associated with a higher risk of recurrence in cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p <0.001) but not low risk (HR 0.62, 95% CI 0.08-4.75, p=0.647). CONCLUSIONS: Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features.

To clamp or not to clamp? Long-term functional outcomes for elective off-clamp laparoscopic partial nephrectomy.

OBJECTIVE: To evaluate whether elective off-clamp laparoscopic partial nephrectomy (LPN) affords long-term renal functional benefit compared with the on-clamp approach. PATIENTS AND METHODS: This is a retrospective review of patients who underwent elective LPN between 2006 and 2011. Patients were followed longitudinally for up to 5 years. In all, 315 patients with radiographic evidence of a solitary renal mass and normal-appearing contralateral kidney underwent elective LPN; 209 were performed on-clamp vs 106 off-clamp. One patient who required conversion from LPN to open PN was excluded from the study. Additionally, four patients in the on-clamp cohort who underwent subsequent radical nephrectomy for local-regional recurrence were excluded from longitudinal functional evaluation after their procedure. The primary objective was to evaluate differences in postoperative estimated glomerular filtration rate (eGFR) between hilar clamping groups. Subgroup analyses were performed for patients with clamp times >30 min and those with baseline renal insufficiency (eGFR <60 mL/min/1.73m(2) ). Risk of developing worsened or new-onset renal insufficiency was also compared. RESULTS: The mean preoperative eGFR was similar between the on-clamp and off-clamp cohorts (80.7 vs 84.1 mL/min/1.73m(2) , P > 0.05). Univariable and multivariable analyses did not show significant differences in postoperative eGFR between both groups among all-comers, those with clamp times >30 min, and patients with baseline renal insufficiency. Risk of chronic kidney disease was not diminished by the off-clamp approach with up to 5 years of follow-up. CONCLUSIONS: Progressive recovery of renal function after hilar clamping in the elective setting eclipses short-term functional benefit achieved with off-clamp LPN by 6 months; there was no significant difference in eGFR or the percentage incidence of chronic kidney disease between the on-clamp and off-clamp cohorts with up to 5 years follow-up. As such, eliminating transient ischaemia during elective LPN does not confer clinical benefit.

Association between systemic inflammatory markers and serum prostate-specific antigen in men without prostatic disease - the 2001-2008 National Health and Nutrition Examination Survey.

BACKGROUND: Serum prostate specific antigen (PSA) may be elevated in otherwise healthy men; systemic inflammation has been associated with cancer. The study of systemic inflammatory markers in men without clinical prostate disease, but with elevated PSA may characterize the subgroup of men at higher risk for subsequent prostate cancer. METHODS: We investigated the associations between systemic inflammatory markers and serum PSA in 3,164 healthy men without prostatic disease, aged >40 years, from the 2001 to 2008 U.S. National Health and Nutrition Examination Survey (NHANES). Serum total PSA levels and concentrations of serum C-reactive protein (CRP) and plasma fibrinogen, neutrophil count, lymphocyte count, and platelet count were recorded. Neutrophil-lymphocyte ratio (NLR) ratio and platelet-lymphocyte (PLR) ratio were calculated. PSA elevation was defined as levels equal or greater than 4 ng/ml. RESULTS: Elevated serum PSA (194 men, 6.1% of the total), was significantly associated with plasma fibrinogen (ORmultiv = 1.88; 95% CI, 1.09-3.25), and NLR (ORmultiv = 1.14; 95% CI, 1.03-1.26), after adjustment for age, smoking, body mass index, education, race, co-morbidities, and use of medications. CONCLUSIONS: Markers of systemic inflammation were associated with elevated PSA in men without known prostatic disease. Future studies are needed to examine these markers' relationship with prostate cancer occurrence and progression.

Multiparametric magnetic resonance imaging outperforms the Prostate Cancer Prevention Trial risk calculator in predicting clinically significant prostate cancer.

BACKGROUND: The Prostate Cancer Prevention Trial risk calculator for high-grade (PCPTHG) prostate cancer (CaP) was developed to improve the detection of clinically significant CaP. In this study, the authors compared the performance of the PCPTHG against multiparametric magnetic resonance imaging (MP-MRI) in predicting men at risk of CaP. METHODS: Men with an abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE) and a suspicious lesion on a 3-Tesla MP-MRI were enrolled prospectively. Three radiologists reviewed and graded all lesions on a 5-point Likert scale. Biopsy of suspicious lesion(s) was performed using a proprietary MRI/transrectal ultrasound fusion-guided prostate biopsy system, after which 12-core biopsy was performed. A genitourinary pathologist reviewed all pathology slides. The performance of PCPTHG was compared with that of MP-MRI in predicting clinically significant CaP. RESULTS: Of 175 men who were eligible for analysis, 64.6% (113 of 175 men) were diagnosed with CaP, including 93 of 113 men (82.3%) who had clinically significant disease. Age, abnormal DRE, PSA, PSA density, prostate size, extraprostatic extension on MRI, apparent diffusion coefficient value, and MRI lesion size were identified as significant predictors of high-grade CaP (all P < .05). The area under the receiver operating characteristic curve of PCPTHG for predicting high-grade CaP was 0.676 (95% confidence interval [CI], 0.592-0.751). By using a risk cutoff of ≥15% for biopsy as, proposed previously for high-grade CaP, sensitivity was 96.4%, specificity was 7.6%, and the false-positive rate was 51.1%. In contrast, the area under the receiver operating characteristic curve of MP-MRI for high-grade CaP was 0.769 (95% CI, 0.703-0.834), and it was 0.812 (95% CI, 0.754-0.869) for clinically significant CaP. CONCLUSIONS: MP-MRI outperforms PCPTHG in predicting clinically significant CaP, and its application may help select patients who will benefit from CaP diagnosis and treatment.

Improving detection of clinically significant prostate cancer: magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy.

PURPOSE: Given the limitations of prostate specific antigen and standard biopsies for detecting prostate cancer, we evaluated the cancer detection rate and external validity of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system used at the National Institutes of Health. MATERIALS AND METHODS: We performed a phase III trial of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system with participants enrolled between 2012 and 2013. A total of 153 men consented to the study and underwent 3 Tesla multiparametric magnetic resonance imaging with an endorectal coil for clinical suspicion of prostate cancer. Lesions were classified as low or moderate/high risk for prostate cancer. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and standard 12-core prostate biopsy were performed and 105 men were eligible for analysis. RESULTS: Mean patient age was 65.8 years and mean prostate specific antigen was 9.5 ng/ml. The overall cancer detection rate was 62.9% (66 of 105 patients). The cancer detection rate in those with moderate/high risk on imaging was 72.3% (47 of 65) vs 47.5% (19 of 40) in those classified as low risk for prostate cancer (p<0.05). Mean tumor core length was 4.6 and 3.7 mm for fusion biopsy and standard 12-core biopsy, respectively (p<0.05). Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detected prostate cancer that was missed by standard 12-core biopsy in 14.3% of cases (15 of 105), of which 86.7% (13 of 15) were clinically significant. This biopsy upgraded 23.5% of cancers (4 of 17) deemed clinically insignificant on 12-core biopsy to clinically significant prostate cancer necessitating treatment. CONCLUSIONS: Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy can improve prostate cancer detection. The results of this trial support the external validity of this platform and may be the next step in the evolution of prostate cancer management.

Single cell network profiling assay in bladder cancer.

The aim of this study was to assess the feasibility of applying the single cell network profiling (SCNP) assay to the examination of signaling networks in epithelial cancer cells, using bladder washings from 29 bladder cancer (BC) and 15 nonbladder cancer (NC) subjects. This report describes the methods we developed to detect rare epithelial cells (within the cells we collected from bladder washings), distinguish cancer cells from normal epithelial cells, and reproducibly quantify signaling within these low frequency cancer cells. Specifically, antibodies against CD45, cytokeratin, EpCAM, and cleaved-PARP (cPARP) were used to differentiate nonapoptotic epithelial cells from leukocytes, while measurements of DNA content to determine aneuploidy (DAPI stain) allowed for distinction between tumor and normal epithelial cells. Signaling activity in the PI3K and MAPK pathways was assessed by measuring intracellular levels of p-AKT and p-ERK at baseline and in response to pathway modulation; 66% (N = 19) of BC samples and 27% (N = 4) of NC samples met the "evaluable" criteria, i.e., at least 400,000 total cells available upon sample receipt with >2% of cells showing an epithelial phenotype. The majority of epithelial cells detected in BC samples were nonapoptotic and all signaling data were generated from identified cPARP negative cells. In four of 19 BC samples but in none of the NC specimens, SCNP assay identified epithelial cancer cells with a quantifiable increase in epidermal growth factor-induced p-AKT and p-ERK levels. Furthermore, preincubation with the PI3K inhibitor GDC-0941 reduced or completely inhibited basal and epidermal growth factor-induced p-AKT but, as expected, had no effect on p-ERK levels. This study demonstrates the feasibility of applying SCNP assay using multiparametric flow cytometry to the functional characterization of rare, bladder cancer cells collected from bladder washing. Following assay standardization, this method could potentially serve as a tool for disease characterization and drug development in bladder cancer and other solid tumors.

Image-guided percutaneous renal cryoablation: preoperative risk factors for recurrence and complications.

OBJECTIVE: To investigate the value of the R.E.N.A.L nephrometry scoring system in predicting treatment success for image-guided percutaneous cryoablation (PCA). PATIENTS AND METHODS: The study included 139 patients with renal masses treated with PCA. Preoperative computed tomography or magnetic resonance images were reviewed by a urology resident. The primary endpoint variable was incomplete treatment or tumour recurrence. R.E.N.A.L. scores were categorized into low (4-6), moderate (7-9), and high (10-12). Logistic regression analysis was conducted to predict tumour recurrence. Additional variables collected included age at surgery, American Society of Anesthesiologists score, lesion size, skin-to-tumour distance, skin-to-hilum distance, and number of treatment cryoprobes. RESULTS: At a median follow-up of 24 months, there were 10 tumour recurrences (six moderate and four high R.E.N.A.L. score categories). Nephrometry score and number of probes used were not associated with recurrence (odds ratio [OR] 1.02, P = 0.9 and P = 0.53, respectively). The tumour distances for patients with recurrence and no recurrence were 10.8 cm and 8.5 cm, respectively (P ≤ 0.05), the skin-to-tumour distance was associated with treatment failure (OR 1.24, P = 0.015); for each unit increase in the mean value, patients were 1.5 times more likely to have a tumour recurrence (95% confidence interval [CI] 1.04-1.72). The model that best predicted complications included the number of probes used (P = 0.002) and R.E.N.A.L. score (OR 1.35, P = 0.027). For each additional probe used, patients were twice as likely to have complications (OR 1.98, 95% CI 1.28-3.05). With each unit increase in R.E.N.A.L. score, patients were 1.5 times more likely to experience a complication (OR 1.49, 95% CI 1.05-2.11). CONCLUSIONS: An increased skin-to-tumour distance is associated with a higher risk of treatment failure after PCA. Furthermore, an increase in both R.E.N.A.L nephrometry score and number of probes used was associated with an increased risk of complications after PCA. The R.E.N.A.L. nephrometry score as a measure of tumour complexity was not associated with tumour recurrence.

Intracorporeal neobladder reconstruction: pressure-flow urodyamic studies in cadaveric orthotopic neobladders.

OBJECTIVE: To determine the pressure-flow characteristics of neobladders created in various configurations that may be constructed intra-abdominally. Complete intracorporeal neobladder construction has been previously described but is limited due to excessive operative time and the need for an advanced laparoscopic skill set. MATERIALS AND METHODS: Four neobladder configurations were constructed, each using 20 cm of human cadaveric small intestine. The standard hand sewn Studer pouch was compared with a circular loop, W-pouch, and U-pouch with stapled anastamoses. Pressure flow studies were completed using the Aquarius TT UDS system (Laborie Medical Technologies, Toronto, Ontario) and each neobladder was filled to a pressure of 50 cm H2O. Neobladder change in pressure, capacity, and overall compliance were determined. RESULTS: The cystometric capacities of the stapled U-pouch, W-pouch, Circle pouch, and Studer pouch were 167.3 mL, 177.5 mL, 114 mL, and 145.2 mL respectively. The first increase in intravesical pressure was at 90.3 mL, 103 mL, 50 mL, and 85 mL. The greatest compliance of 3.81 mL/cmH2O was demonstrated in the U-pouch, with the W-pouch revealing a compliance of 3.44 mL/cmH2O. The least compliant neobladder was the circle pouch (2.24 mL/cmH20) followed by the standard Studer pouch (2.94 mL/cmH2O). CONCLUSION: The construction of an orthotopic neobladder must not only be technically feasible but maintain adequate capacity and compliance for optimal functioning. Pressure-flow studies demonstrated equivalent results in alternate neobladder configurations. Additional data is needed to determine feasibility in vivo.

Delayed haemorrhage after laparoscopic partial nephrectomy: frequency and angiographic findings.

OBJECTIVES: • To determine the frequency of delayed postoperative haemorrhage requiring selective angioembolization (SAE) after laparoscopic partial nephrectomy (LPN). • To describe the clinical presentation and characterize the angiographic findings encountered in this setting. PATIENTS AND METHODS: • Prospective data from 640 LPNs performed between August 1993 and May 2009 were retrospectively analyzed, from which patients with delayed postoperative haemorrhage (defined as 'gross haematuria ≥ 7 days postoperatively that persists for more than 24 h') and requiring SAE were identified. • Clinicopathological, preoperative and perioperative factors were reviewed. • Selective catheterization and angiography of the renal artery was performed for persistent gross haematuria and for haemodynamic instability associated with a significant drop in haematocrit level. • Arteries feeding the bleeding site were identified and embolized with endovascular coils. RESULTS: • Patients presented with delayed haemorrhage between 7 and 30 days after surgery. SAE was required in 13 patients (2%) for delayed postoperative bleeding. • Of the 640 LPNs, 68 (10.6%) were performed without hilar occlusion ('off-clamp') of whom one (1.5%) had a delayed haemorrhage, which was successfully embolized. • For patients with and without delayed haemorrhage after LPN, the mean tumour size was 2.7 cm and 3.3 cm (P= 0.31), the mean warm ischaemia time was 28.2 min and 14.3 min (P < 0.001), and the mean estimated blood loss 403.8 mL and 308.2 mL (P= 0.26), respectively. • Percutaneous angiography showed renal artery pseudoaneurysm in 10 patients and arterial contrast extravasation in three patients, two of whom also had an arteriovenous fistula. • Following embolization, creatinine levels remained stable in all patients. CONCLUSIONS: • Clinically significant delayed postoperative bleeding after LPN occurs in a small percentage of patients. • Angiography will accurately make the diagnosis of RAP or AVF and SAE is safe and effective procedure that allows for preservation of renal function.

Feasibility and Utility of Mobile Applications for the Evaluation of Urology Residents' Surgical Competence.

OBJECTIVE: To provide real-time assessment and feedback on the competency of urology residents' surgical skill via mobile applications and examine their feasibility and utility. MATERIALS AND METHODS: Two mobile application-based systems (SIMPL and myTIPreport) were sequentially implemented for the case-by-case assessment of residents' performance of surgical skills at a single institution. Data was collected regarding residents' perception of their feedback pre- and post-implementation of the applications. Faculty were surveyed after their implementation to determine their feasibility and utility. RESULTS: 297 individual evaluations were completed with SIMPL and 822 with myTIPreport over four and eleven months respectively. Post-implementation, residents showed significantly improved perceptions regarding the quantity and personalization of surgical skill feedback (P = .043 and .005 respectively). A majority (75%) of the faculty found the mobile applications feasible to use, an improvement compared to prior methods of resident evaluation, and would recommend continued use. CONCLUSION: This study represents the first documented use of real-time surgical competency assessment in urology. The use of mobile applications to evaluate urology residents' surgical competency in clinical practice is both feasible and useful. Their use may allow for more individualized surgical skill teaching during training and for the verification of the surgical skills necessary to practice autonomously.

Extracapsular extension on multiparametric magnetic resonance imaging better predicts pT3 disease at radical prostatectomy compared to perineural invasion on biopsy.

INTRODUCTION: Risk assessment for non-organ-confined prostate cancer (PCa) is important in the surgical planning for radical prostatectomy (RP). Perineural invasion (PNI) on prostate biopsy has been associated with adverse pathological outcomes at prostatectomy. Similarly, the identification of suspected extracapsular extension (ECE) on multiparametric magnetic resonance imaging (mpMRI) has been shown to predict non-organ-confined disease. However, no prior study has compared these factors in predicting adverse pathology at prostatectomy. We evaluated mpMRI ECE and prostate biopsy PNI on multivariable analysis to determine their ability to predict pathological stage at time of RP. METHODS: We retrospectively investigated the prostatectomy database at our institution to identify men who underwent prostate biopsy with pre-biopsy mpMRI and subsequent RP from 2013-2017. Multivariable regression analysis was performed to compare the association of mpMRI ECE (mECE) and PNI on prostate biopsy on the likelihood of finding pT3 disease on pathology post-prostatectomy. RESULTS: Of a total 454 RP between 2013 and 2017, 191 patients met our inclusion criteria. Stage pT2 and pT3+ were found in 120 (62.8%) and 71 (37.2%) patients, respectively. Patients with mECE had 4.84 cumulative odds of worse pathological stage on RP (p=0.045) compared to PNI on biopsy, which showed cumulative odds of 2.25 (p=0.048). When controlling only for those patients without PNI, mECE was still found to be a significant predictor of pT3 disease at RP (p=0.030); however, in patients without mECE, PNI was not significant (p=0.062). CONCLUSIONS: While mECE and biopsy PNI were both associated with worse pathological stage on RP, mECE had significantly higher cumulative odds compared to PNI. The significant predictive ability of mECE adds further clinical value to the use of mpMRI in PCa management. While validation in a larger cohort is required, these factors have important clinical implications with regards to early diagnosis of advanced disease and surgical planning.

Use of a Risk Stratification Tool to Guide Evaluation of Patients With Asymptomatic Microscopic Hematuria.

OBJECTIVE: To determine if use of the hematuria risk index can reduce testing and cost, while maintaining equivalent lesion detection in patients with asymptomatic microscopic hematuria. MATERIALS AND METHODS: Retrospective cohort study of 1049 patients at single institution. Hematuria risk index score was calculated based on clinical factors including age, sex, smoking history, and degree of hematuria for each patient along with evaluation studies performed and total number of tumors discovered. Cost benefit analysis was performed based on published Medicare averages. RESULTS: Tumor detection rate in overall, low-risk, and moderate-risk groups were 1.2%, 0%, and 2.96% at a total cost of $408,376. When low-risk group is not screened cost decreases to $166,252 with no lesions missed. The cost to discover one lesion/cancer in the overall group was $34,031.3, the cost to find one high-grade clinically significant lesion/cancer was $136,125.3 for the overall group. When the low-risk group was removed, the cost to find a high-grade clinically significant lesion/cancer decreased to $55,417.3 without missing any significant lesions. Ultrasound may be utilized instead of computed tomography with minimal loss of lesion detection in select moderate risk patients. CONCLUSION: None of the low-risk hematuria risk patients were diagnosed with any lesions, as such these patients may not need an evaluation. Furthermore, by utilizing a risk-stratified approach to the assessment of asymptomatic microscopic hematuria health care costs can be significantly decreased with limited negative consequences in terms of lesion detection.

Radiation therapy approaches to the treatment of high-risk prostate cancer.

Radiation therapy modalities have been shown to offer patients a nonoperative option for definitive treatment of localized prostate cancer as well as options for adjuvant or salvage therapy in high-risk prostate cancer patients. In patients with high-risk, localized disease, radiation therapy with or without adjuvant hormonal therapy is considered an excellent treatment option because of its efficacy within the prostate and among local periprostatic structures, addressing micrometastatic disease. Following radical prostatectomy in patients with high-risk or recurrent disease, radiotherapy can increase oncologic efficacy in both the adjuvant and salvage setting. Continued studies are underway to address ongoing concerns of sparing surrounding tissues unnecessary radiation while administering high-dose radiation to the prostate and targeted periprostatic structures. Newer technologies are using real-time imaging and computer-simulated motion calculation to adjust for physiological organ motion with respect to bony landmarks classically used to map areas of radiation administration.

Circulating microRNAs in plasma before and after radical prostatectomy.

PURPOSE: MicroRNAs (miRNAs/miRs) as circulating biomarkers for prostate cancer have yet to be determined. We examined whether circulating miRNAs in plasma could be employed as biomarkers of disease among men treated for prostate cancer by radical prostatectomy (RP). METHODS: The expression of 17 preselected circulating miRNAs associated with prostate cancer (miR-381, -34a, -365, -122, -375, -1255b, -34b, -450b-5p, -885-5p, -1260, -150, -378, -671-3p, -148a, and -224) or high-grade prostate cancer (miR-28 and -100) in plasma at prostate biopsy was examined in pre- and post-RP plasma of prostate cancer patients using real-time PCR and compared using Wilcoxon signed-ranked test. Wilcoxon rank sum test was used to compare the expression of miRNAs in pre-RP plasma between pathologic tumor stage (T2 vs. T3) and Gleason score (6-7 [3 + 4] vs. ≥ 7 [4 + 3]) groups. Partial correlation coefficient between the expression of miRNAs in pre-RP plasma and serum prostate-specific antigen (PSA) level at RP, adjusting for age, was calculated. RESULTS: Twenty-nine men, aged 43 to 77 years, were included. Median follow-up time after RP was 55 days. There was no significant change in the expression of miRNAs in plasma from before to after RP. However, higher expression of miR-34a, -378, and 450b-5p in pre-RP plasma was observed among T3 compared to T2 patients (P values = 0.01). Overall, there were no statistically significant relationships observed between the expression of these circulating miRNAs and Gleason score and serum PSA at RP. CONCLUSIONS: There was no significant change in the expression of circulating miRNAs in plasma from before to approximately 2 months after RP. This finding may be due to the lack of immediate effect RP may have on the expression of circulating miRNAs. However, higher expression of miR-34a, -378, and -450b-5p in plasma was found among patients with more advanced disease at RP. A longer follow-up time after RP is warranted to investigate RP's possible influence on circulating miRNAs among men treated for prostate cancer and to evaluate miRNAs' diagnostic potential for prostate cancer.

The UOK 257 cell line: a novel model for studies of the human Birt-Hogg-Dubé gene pathway.

The establishment, characterization, and tumorigenicity of a new epithelial cell line (UOK 257) derived from human renal carcinoma of an individual with Birt-Hogg-Dubé (BHD) syndrome are reported. Unlike other established renal tumor cell lines from sporadic renal cell carcinoma, this is the first established renal tumor cell line of BHD, an inheritable neoplastic syndrome. The isolated tumor cells display loss of contact inhibition in vitro, and produce subcutaneous tumors in mouse xenografts. Histopathologic, ultrastructural, and cytogenetic characterizations of the established tumor cells are reported. Cytogenetic analysis using spectral karyotyping on UOK 257 cells revealed 17p loss and a near-triploid and aneuploid karyotype with multiple fluorescence in situ hybridization analysis using a locus-specific gene probe for MYC. The result demonstrates that the established tumor cells consist of two cell populations, one containing four and one containing five copies of the MYC oncogene.

Is the biopsy Gleason score important in predicting outcomes for patients after radical prostatectomy once the pathological Gleason score is known?

OBJECTIVE: To evaluate whether specific preoperative variables might better predict the concordance between biopsy and radical prostatectomy (RP) Gleason grade, and to assess the effect of the biopsy Gleason score (bGS) when controlling for the pathological GS (pGS) on clinical outcomes in patients undergoing RP. PATIENTS AND METHODS: Between 1989 and 1998, 1088 men had RP at our institution, with a median follow-up of 56 months. To evaluate the independent effect of bGS within categories of pGS, we stratified the sample by pGS (three categories;