Erosion of IPP components into bladder lumen and prostatic urethra.

The incidence of erosion of inflatable penile prosthesis (IPP) components into adjacent organs is low (<0.1 %). During a transurethral resection of the prostate (TURP) in a patient with prior IPP placement, we encountered IPP tubing that had eroded into the prostate. The pump and cylinders were later explanted through a penoscrotal approach, with the reservoir drained and retained with plan for follow up cystoscopy in 4-6 weeks. Cystoscopy 1 month later demonstrated reservoir erosion into the bladder lumen. An open cystotomy was performed to retrieve the reservoir. This is the first reported case of IPP tubing eroding into the prostate.

NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

Preparation and Utilization of Freshly Isolated Human Detrusor Smooth Muscle Cells for Characterization of 9-Phenanthrol-Sensitive Cation Currents.

Detrusor smooth muscle (DSM) cells present within the urinary bladder wall ultimately facilitate urine storage and voiding. Preparation of the viable, fresh, and isolated DSM cells presents an important technical challenge whose achievement provides optimal cells for subsequent functional and molecular studies. The method developed and elaborated herein, successfully used by our group for over a decade, describes dissection of human urinary bladder specimens obtained from open bladder surgeries followed by an enzymatic two-step treatment of DSM pieces and mechanical trituration to obtain freshly isolated DSM cells. The initial step involves dissection to separate the DSM layer (also known as muscularis propria) from mucosa (urothelium, lamina propria, and muscularis mucosa) and the adjacent connective, vascular, and adipose tissues present. The DSM is then cut into pieces (2-3 mm x 4-6 mm) in nominal Ca2+-containing dissection/digestion solution (DS). DSM pieces are next transferred to and sequentially treated separately with DS containing papain and collagenase at ~37 °C for 30-45 min per step. Following washes with DS containing enzyme-free bovine serum and trituration with a fire-polished pipette, the pieces release single DSM cells. Freshly isolated DSM cells are ideally suited for patch-clamp electrophysiological and pharmacological characterizations of ion channels. Specifically, we show that the TRPM4 channel blocker 9-phenanthrol reduces voltage-step evoked cation currents recorded with the amphotericin-B perforated patch-clamp approach. DSM cells can also be studied by other techniques such as single cell RT-PCR, microarray analysis, immunocytochemistry, in situ proximity ligation assay, and Ca2+ imaging. The main advantage of utilizing single DSM cells is that the observations made relate directly to single cell characteristics revealed. Studies of freshly isolated human DSM cells have provided important insights characterizing the properties of various ion channels including cation-permeable in the urinary bladder and will continue as a gold standard in elucidating DSM cellular properties and regulatory mechanisms.

Effect of Molar Preparation Axial Height on Retention of Adhesively-luted CAD-CAM Ceramic Crowns.

PURPOSE: To evaluate the effect of axial wall height (AWH) on failure resistance of CAD-CAM adhesively-bonded, all-ceramic crowns on molar preparations with a conservative total occlusal convergence (TOC). MATERIALS AND METHODS: 60 newly extracted maxillary third molars were divided into 5 groups (n = 12) and prepared for all-ceramic crowns with occlusal cervical AWH of 0, 1, 2, 3, and 4 mm, all containing a conservative 10-degree TOC. Scanned preparations were fitted with lithium-disilicate glass-ceramic crowns using a self-adhesive resin-composite luting agent after intaglio surface preparation with hydrofluoric acid and silane. Specimens were stored at 37°C/98% humidity for 24 h and tested to failure at a 45-degree angle applied to the palatal cusp on a universal testing machine. Mean results were analyzed using ANOVA and Tukey's test (p = 0.05). RESULTS: Preparations containing 2, 3, and 4 mm AWH demonstrated similar and higher failure resistance than the 0- and 1-mm axial wall height groups. CONCLUSIONS: Under the conditions of this study, evidence is presented that under certain conditions CAD-CAM adhesive technology may compensate for less than optimal AWH. Based on both failure load results and failure mode analysis, adhesively-luted maxillary molar CAD-CAM crowns based on a preparation containing 10-degree TOC require at least 2 mm AWH for adequate resistance and retention. However, adoption of these findings is cautioned until both fatigue analysis and appropriate clinical evidence has been provided.

Rising Serum Uric Acid Level Is Negatively Associated with Survival in Renal Cell Carcinoma.

Aim and Background: To investigate the association of serum uric acid (SUA) levels along with statin use in Renal Cell Carcinoma (RCC), as statins may be associated with improved outcomes in RCC and SUA elevation is associated with increased risk of chronic kidney disease (CKD). Methods: Retrospective study of patients undergoing surgery for RCC with preoperative/postoperative SUA levels between 8/2005-8/2018. Analysis was carried out between patients with increased postoperative SUA vs. patients with decreased/stable postoperative SUA. Kaplan-Meier analysis (KMA) calculated overall survival (OS) and recurrence free survival (RFS). Multivariable analysis (MVA) was performed to identify factors associated with increased SUA levels and all-cause mortality. The prognostic significance of variables for OS and RFS was analyzed by cox regression analysis. Results: Decreased/stable SUA levels were noted in 675 (74.6%) and increased SUA levels were noted in 230 (25.4%). A higher proportion of patients with decreased/stable SUA levels took statins (27.9% vs. 18.3%, p = 0.0039). KMA demonstrated improved 5- and 10-year OS (89% vs. 47% and 65% vs. 9%, p < 0.001) and RFS (94% vs. 45% and 93% vs. 34%, p < 0.001), favoring patients with decreased/stable SUA levels. MVA revealed that statin use (Odds ratio (OR) 0.106, p < 0.001), dyslipidemia (OR 2.661, p = 0.004), stage III and IV disease compared to stage I (OR 1.887, p = 0.015 and 10.779, p < 0.001, respectively), and postoperative de novo CKD stage III (OR 5.952, p < 0.001) were predictors for increased postoperative SUA levels. MVA for all-cause mortality showed that increasing BMI (OR 1.085, p = 0.002), increasing ASA score (OR 1.578, p = 0.014), increased SUA levels (OR 4.698, p < 0.001), stage IV disease compared to stage I (OR 7.702, p < 0.001), radical nephrectomy (RN) compared to partial nephrectomy (PN) (OR 1.620, p = 0.019), and de novo CKD stage III (OR 7.068, p < 0.001) were significant factors. Cox proportional hazard analysis for OS revealed that increasing age (HR 1.017, p = 0.004), increasing BMI (Hazard Ratio (HR) 1.099, p < 0.001), increasing SUA (HR 4.708, p < 0.001), stage III and IV compared to stage I (HR 1.537, p = 0.013 and 3.299, p < 0.001), RN vs. PN (HR 1.497, p = 0.029), and de novo CKD stage III (HR 1.684, p < 0.001) were significant factors. Cox proportional hazard analysis for RFS demonstrated that increasing ASA score (HR 1.239, p < 0.001, increasing SUA (HR 9.782, p < 0.001), and stage II, III, and IV disease compared to stage I (HR 2.497, p < 0.001 and 3.195, p < 0.001 and 6.911, p < 0.001) were significant factors. Conclusions: Increasing SUA was associated with poorer outcomes. Decreased SUA levels were associated with statin intake and lower stage disease as well as lack of progression to CKD and anemia. Further investigation is requisite.

Acupuncture for Analgesia During Transurethral Resection of Bladder Tumor.

Background: Acupuncture has been widely studied, and theories regarding its analgesic mechanism of action have been proposed. It has been used for procedural analgesia; however, no reports of its use in urologic surgery have been reported. In this case report, we demonstrate how acupuncture can be used as an alternative to general anesthesia for transurethral resection of bladder tumor (TURBT). This may serve as an attractive option for bladder cancer patients with medical comorbidities, which predispose them to high risk for general anesthesia. Case Presentation: A 65-year-old Caucasian female with toxicant-induced loss of tolerance (TILT) was found to have a bladder mass. TURBT was discussed, and in light of her TILT syndrome, she elected to undergo the procedure with acupuncture in lieu of general anesthesia for fear of an adverse reaction. Acupuncture was performed by a trained practitioner with therapeutic needles placed in the ears, hands, abdomen, and lower extremities bilaterally. She was subsequently taken to the operating room where we performed a TURBT of a bladder tumor overlying the left ureteral orifice. The procedure was generally well tolerated and the patient experienced mild pain. There were no perioperative complications. The tumor was estimated to be 3 cm in largest diameter, and a total of 8 g of aggregate tissue was sent to our pathologists. Pathology analysis demonstrated adequate resection with detrusor muscle present in the sample. The bladder tumor was low-grade papillary urothelial cell carcinoma (Stage Ta). She has had tumor recurrence and has undergone repeat TURBT, but to date, she is 22 months free of bladder cancer. Conclusion: In this case report, we demonstrate that acupuncture is a safe and effective alternative to general anesthesia for patients undergoing TURBT. Since tobacco use is prevalent among bladder cancer patients, many of these individuals have associated medical comorbidities, which predispose them to high risk with general anesthesia. Therefore, acupuncture may serve as an attractive alternative for certain patients in this population.

Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer.

Androgen receptor (AR) mediates the growth of prostate cancer throughout its course of development, including in abnormal splice variants (AR-SV)-driven advanced stage castration-resistant disease. AR stabilization by androgens makes it distinct from other steroid receptors, which are typically ubiquitinated and degraded by proteasomes after ligand binding. Thus, targeting AR in advanced prostate cancer requires the development of agents that can sustainably degrade variant isoforms for effective therapy. Here we report the discovery and characterization of potent selective AR degraders (SARD) that markedly reduce the activity of wild-type and splice variant isoforms of AR at submicromolar doses. Three SARDs (UT-69, UT-155, and (R)-UT-155) bind the amino-terminal transcriptional activation domain AF-1, which has not been targeted for degradation previously, with two of these SARD (UT-69 and UT-155) also binding the carboxy-terminal ligand binding domain. Despite different mechanisms of action, all three SARDs degraded wild-type AR and inhibited AR function, exhibiting greater inhibitory potency than the approved AR antagonists. Collectively, our results introduce a new candidate class of next-generation therapeutics to manage advanced prostate cancer. Cancer Res; 77(22); 6282-98. ©2017 AACR.

Impact of tumor histology and grade on treatment success of percutaneous renal cryoablation.

BACKGROUND: We analyzed oncological outcomes in patients who underwent percutaneous renal cryoablation (PRC) with documented renal cell carcinoma (RCC) by perioperative biopsy. METHODS: Multicenter retrospective analysis of 153 patients [median follow-up 48 months] who underwent PRC from 09/2005 to 08/2014 was performed. We divided the cohort into patients who developed recurrence versus no recurrence. Kaplan-Meier analyses examined recurrence-free survival (RFS) according to grade and histology. Multivariable analysis (MVA) was performed to identify factors associated with tumor recurrence. RESULTS: One hundred and fifty-three patients were analyzed [18 patients (11.8 %) with recurrence and 135 (88.2 %) patients without recurrence]. There were no differences between the groups with respect to demographics, RENAL score, and number of probes utilized. Recurrence group had larger tumor size (3.1 vs. 2.4 cm; p = 0.011), upper pole tumor location (p = 0.016), and greater proportions of high-grade tumor (33 vs. 0.7 %; p < 0.001) and clear cell histology (77.8 vs. 45.9 %; p = 0.011). Four-year RFS was 100 versus 80 % for grade 1 versus grade 2/3 tumors (p = 0.0002), and 97 versus 88 % for other RCC versus clear cell RCC (p = 0.07). MVA demonstrated tumor size >3 cm (OR 2.46; p = 0.019), clear cell histology (OR 2.12; p = 0.027), and high tumor grade (OR 2.33, p < 0.001) as independent risk factors associated with tumor recurrence. CONCLUSIONS: Association of higher grade and clear cell histology with recurrence and progression suggests need for increased emphasis on preoperative risk stratification by biopsy, with grade 1 and non-clear cell RCC being associated with improved treatment success than higher grade and clear cell RCC.

NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panel's most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.

Association of rise in C-reactive protein with decline in renal function following partial nephrectomy.

INTRODUCTION: To investigate association of C-reactive protein (CRP), a marker of systemic inflammation, with renal functional decline patients undergoing partial nephrectomy (PN) for renal mass. MATERIALS AND METHODS: Retrospective study of patients who underwent PN between February 2006-March 2011, with ≥ 6 months follow up. Data was analyzed between two groups: CRP increase ≥ 0.5 mg/L from 6 months postoperative ('CRP rise,' CRPR), versus no CRP increase = 0.5 ('CRP stable,' CRPS). Primary outcome was change in estimated glomerular filtration rate (ΔeGFR, mL/min/1.73 m²), with de novo postoperative stage III chronic kidney disease (stage III-CKD, eGFR < 60 mL/min/1.73 m²) being secondary. Multivariable analysis (MVA) was conducted to identify risk factors for development of de novo stage III-CKD. RESULTS: A total of 243 patients (206 CRPS/37 CRPR) were analyzed. Demographics and R.E.N.A.L. nephrometry scores were similar. CRPR had significantly higher median ΔeGFR (-13.7 versus -32.0 mL/min/1.73 m², p < 0.001) and de novo stage III-CKD at last follow up (43.2% vs. 3.7%, p < 0.001). Median time to CRP rise was 10 (IQR 6.5-12) months. Median time from CRP rise to de novo stage III-CKD was 9 (IQR 7.5-11) months. MVA found RENAL score (OR 1.89, p = 0.001), hypertension (OR 4.75, p = 0.016), and CRP rise (OR 55.76, p < 0.001) were associated with de novo stage III-CKD. Sensitivity of CRP increase ≥ 0.5 for predicting CKD was 69.6%, specificity 93.3%, positive predictive value 55.2%, and negative predictive value 96.3%. CONCLUSION: Rise in CRP postoperatively is independently associated with renal functional decline after PN and may be useful in identifying patients to evaluate for renoprotective strategies. Further studies are requisite to clarify etiology of this association.

NCCN Clinical Practice Guidelines Prostate Cancer Early Detection, Version 2.2015.

Prostate cancer represents a spectrum of disease that ranges from nonaggressive, slow-growing disease that may not require treatment to aggressive, fast-growing disease that does. The NCCN Guidelines for Prostate Cancer Early Detection provide a set of sequential recommendations detailing a screening and evaluation strategy for maximizing the detection of prostate cancer that is potentially curable and that, if left undetected, represents a risk to the patient. The guidelines were developed for healthy men who have elected to participate in the early detection of prostate cancer, and they focus on minimizing unnecessary procedures and limiting the detection of indolent disease.

Prostate cancer early detection, version 1.2014. Featured updates to the NCCN Guidelines.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for men choosing to participate in an early detection program for prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Overall, the 2014 update represents a more streamlined and concise set of recommendations. The panel stratified the age ranges at which initiating testing for prostate cancer should be considered. Indications for biopsy include both a cutpoint and the use of multiple risk variables in combination. In addition to other biomarkers of specificity, the Prostate Health Index has been included to aid biopsy decisions in certain men, given recent FDA approvals.

Impact of renal surgery for cortical neoplasms on lipid metabolism.

OBJECTIVE: To examine the incidence of and risk factors for development of hyperlipidaemia in patients undergoing radical nephrectomy (RN) or partial nephrectomy (PN) for renal cortical neoplasms, as hyperlipidaemia is a major source of morbidity in chronic kidney disease (CKD). PATIENTS AND METHODS: We conducted a two-centre retrospective analysis of 905 patients (mean age 57.5 years, mean follow-up 78 months), who underwent RN (n = 610) or PN (n = 295) between July 1987 and June 2007. Demographics, preoperative and postoperative hyperlipidaemia were recorded. De novo hyperlipidaemia was defined as that ocurring ≥6 months after surgery in cases where laboratory values met National Cholesterol Education Program Adult Treatment Panel III definitions. The Kaplan-Meier method was used to assess freedom from de novo hyperlipidaemia. Multivariable analysis was conducted to determine the risk factors for de novo hyperlipidaemia. RESULTS: There were no significant differences with respect to demographics, preoperative glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) (P = 0.123) and hyperlipidaemia (P = 0.144). Tumour size (cm) was significantly larger in the RN group vs the PN group (7.0 vs 3.7; P < 0.001). Significantly greater postoperative GFR <60 mL/min/1.73 m(2) was noted in the RN group (45.7 vs 18%, P < 0.001). Significantly, more de novo hyperlipidaemia developed in the RN group than in the PN group (23 vs 6.4%; P < 0.001). The mean time to development of hyperlipidaemia was longer for PN than for RN (54 vs 44 months; P = 0.03). Five-year freedom from de novo hyperlipidaemia probability was 76% for RN vs 96% for PN (P < 0.001). Multivariable analysis showed that RN (odds ratio [OR] 2.93; P = 0.0107), preoperative GFR <60 mL/min/1.73 m(2) (OR 1.98; P = 0.037) and postoperative GFR <60 mL/min/1.73 m(2) (OR 7.89; P < 0.001) were factors associated with hyperlipidaemia development. CONCLUSION: Patients who underwent RN had a significantly higher incidence of and shorter time to development of de novo hyperlipidaemia. RN and pre- and postoperative eGFR <60 mL/min/1.73 m(2) were associated with development of hyperlipidaemia. Further follow-up and prospective investigation are necessary to confirm these findings.

National trends in hospitalization from indwelling urinary catheter complications, 2001-2010.

PURPOSE: The purpose of this study is to investigate national trends in hospitalization from indwelling urinary catheters complications from 2001 to 2010. MATERIALS AND METHODS: The Healthcare Utilization Project Nationwide Inpatient Sample database was analyzed for this study. We examine hospitalization rates, patient demographics, hospital stays, insurance provider, hospital type, geographic location, and septicemia rates of patients hospitalized for indwelling urinary catheter complications from 2001 to 2010. RESULTS: Hospitalization from indwelling urinary catheters almost quadrupled from 11,742 in 2001 to 40,429 in 2010. The increases have been due to patients who are older and predominantly male compared to all hospitalization. The "national bill" increased from $213 million to $1.3 billion (a factor of 6) after adjusting for inflation. Most patients had urinary tract infections, 77 % in 2001 and 87 % in 2010. Septicemia in indwelling urinary catheter hospitalization patients has increased from 21 % in 2001 to 40 % in 2010. In 2010, secondary diseases associated with hospitalization due to indwelling urinary catheters included urinary tract infections (86.5 %), adverse effects of medical care (61.9 %), bacterial infection (48.6 %), and septicemia (40.3 %). CONCLUSIONS: Hospitalization due to indwelling urinary catheter complications has almost quadrupled from 11,742 in 2001 to 40,429 in 2010, and the majority of patients had urinary tract infections. Septicemia is of particular concern since rates have almost doubled (from 21 to 40 % over the period) in these patients. The specific medical indication for urinary catheters used postoperatively should be scrutinized, and the duration of placement should be minimized to reduce future complication rates.

RENAL nephrometry score is associated with complications after renal cryoablation: a multicenter analysis.

OBJECTIVE: To analyze outcomes and complications of percutaneous (PRC) and laparoscopic renal cryoablation (LRC) using the radius, endophytic, nearness to collecting system, anterior/posterior, and location (RENAL) nephrometry system. METHODS: Retrospective multicenter analysis of 154 consecutive patients who underwent either ultrasound-guided LRC (n = 88) or computed tomography (CT)-guided PRC (n = 66) from March 2003 to December 2011. RENAL score and demographics were compared to postoperative complications (Clavien). Multivariable analysis was carried out for factors associated with development of postprocedure complications. RESULTS: Mean age was 68 years (94 men/60 women). Median follow-up was 34 months (range 23.6-45.6 months). Mean tumor size was 2.6 ± 1 cm. Mean RENAL score was 5.2 ± 1.4. Differences in (A)nterior/posterior component and (H)ilar domain of the RENAL scores were noted, with PRC favoring posterior tumors and hilar lesions compared to LRC (P < .001 and P = .044, respectively). There were 14.9% complications, all of which were low-grade (Clavien 1,2). There were no differences in complications between LRC and PRC (15.9% vs 13.6%, P = .82). Most common complication type was hemorrhagic in 9 of 154 patients (5.8%); significant increase in the hemorrhagic complication rate was noted for patients with "N" ("nearness") component score of 2 or 3 (5/36, or 13.9%), compared to patients with "N" score of 1 (4/115 or 3.5%, P = .033). multivariable analysis demonstrated that increasing RENAL score was associated with postprocedure complications (odds ratio [OR] = 1.37, P = .025). When separated into individual domains, multivariable analysis revealed that "N" score 3 was significantly associated with postoperative complications (OR 16.15, P = .027). CONCLUSION: Increasing RENAL score was associated development of postprocedure complications after renal cryotherapy. Further investigation is requisite to elucidate the role of RENAL nephrometry score in risk stratification prior to renal cryotherapy.

Does radical nephrectomy increase the risk of erectile dysfunction compared with partial nephrectomy? A cohort analysis.

UNLABELLED: Study Type - Therapy (prospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Erectile dysfunction (ED) is a form of endothelial dysfunction that is prevalent in patients with chronic kidney disease (CKD). We hypothesized that partial nephrectomy (PN) would limit development of ED compared with radical nephrectomy (RN), primarily due to renal function preservation, and found that patients undergoing RN had significantly higher de novo ED compared with a contemporary, well-matched cohort undergoing PN; in addition to RN, hypertension, CKD and diabetes mellitus were associated with developing ED. To our knowledge, this is the first study demonstrating an increased risk of ED after RN compared with PN. OBJECTIVES: • To evaluate prevalence and risk factors for development of erectile dysfunction (ED) in patients who underwent radical nephrectomy (RN) and partial nephrectomy (PN). • ED is a form of endothelial dysfunction that is prevalent in patients with chronic kidney disease (CKD). PN confers superior renal functional preservation compared with RN; however, the impact on ED is unclear. METHODS: • This was a retrospective study of 432 patients (264 RN/168 PN, mean age 58 years, mean follow-up 5.8 years) who underwent surgery for renal tumours between January 1998 and December 2007. • The primary outcome was rate of de novo ED postoperatively. Secondary outcomes included development of CKD (estimated GFR < 60 mL/min/1.73 m(2) ) and response to phosphodiesterase-5 inhibitors. • Multivariate analysis was performed to determine risk factors for de novo ED postoperatively. RESULTS: • RN and PN groups had similar demographics and comorbidities. • Tumour size (cm) was larger for RN (RN 7.0 vs PN 3.7, P < 0.001) and more preoperative ED existed in PN vs RN (P= 0.042). No differences were observed for preoperative CKD, hyperlipidaemia and diabetes mellitus. • Postoperatively, higher rates of de novo ED (29.5% vs 9.5%, P < 0.001) and CKD (33.0% vs 9.8%, P < 0.001) developed in RN vs PN cohorts, respectively. • Of men with ED, 63% responded to phosphodiesterase inhibitors, without significant difference between the two groups (P= 0.896). • Multivariate analysis demonstrated de novo ED to be associated with RN (odds ratio [OR] 3.56, P < 0.001), hypertension (OR 2.32, P= 0.014), preoperative (OR 8.77, P < 0.001) and postoperative (OR 2.64, P= 0.001) CKD, and postoperative diabetes mellitus (OR 2.93, P < 0.001). CONCLUSIONS: • Patients undergoing RN had significantly higher de novo ED compared with a contemporary, well-matched cohort undergoing PN. In addition to RN, hypertension, CKD and diabetes mellitus were associated with developing ED. • Further investigation on effects of surgically induced nephron loss on ED is requisite.

Nomogram to predict prostate cancer diagnosis on primary transrectal ultrasound-guided prostate biopsy in a contemporary series.

OBJECTIVE: Transrectal ultrasound-guided biopsy (TRUSB) remains the mainstay for prostate cancer (CaP) diagnosis. Numerous variables have shown associations with development of CaP. We present a nomogram that predicts the probability of detecting CaP on TRUSB. METHODS: After obtaining institutional review board approval, all patients undergoing primary TRUSB for CaP detection at a single center at our institution between 2/2000 and 9/2007 were reviewed. Patients undergoing repeat biopsies were excluded, and only the first biopsy was included in the analysis. Variables included age at biopsy, race, clinical stage, prostate specific antigen (PSA), number of cores removed, TRUS prostate volume (TRUSPV), body mass index, family history of CaP, and pathology results. S-PLUS 2000 statistical software was utilized with p < 0.05 considered significant. Cox proportional hazards regression models with restricted cubic splines were utilized to construct the nomogram. Validation utilized bootstrapping, and the concordance index was calculated based on these predictions. RESULTS: A total of 1,542 consecutive patients underwent primary TRUSB with a median age of 64.2 years (range 34.9-89.2 years), PSA of 5.7 ng/ml (range 0.3-3,900 ng/ml), number of cores removed of 8.0 (range 1- 22) and TRUSPV of 36.4 cm(3) (range 9.6-212.0 cm(3)). CaP was diagnosed in 561 (36.4%) patients. A nomogram was constructed incorporating age at biopsy, race, PSA, body mass index, clinical stage, TRUSPV, number of cores removed, and family history of CaP. The concordance index when validated internally was 0.802. CONCLUSIONS: We have developed and internally validated a model predicting cancer detection in men undergoing TRUSB in a contemporary series. This model may assist clinicians in risk-stratifying potential candidates for TRUSB, potentially avoiding unnecessary or low-probability TRUSB.

Chemoresistance in prostate cancer cells is regulated by miRNAs and Hedgehog pathway.

Many prostate cancers relapse due to the generation of chemoresistance rendering first-line treatment drugs like paclitaxel (PTX) ineffective. The present study aims to determine the role of miRNAs and Hedgehog (Hh) pathway in chemoresistant prostate cancer and to evaluate the combination therapy using Hh inhibitor cyclopamine (CYA). Studies were conducted on PTX resistant DU145-TXR and PC3-TXR cell lines and clinical prostate tissues. Drug sensitivity and apoptosis assays showed significantly improved cytotoxicity with combination of PTX and CYA. To distinguish the presence of cancer stem cell like side populations (SP), Hoechst 33342 flow cytometry method was used. PTX resistant DU145 and PC3 cells, as well as human prostate cancer tissue possess a distinct SP fraction. Nearly 75% of the SP cells are in the G0/G1 phase compared to 62% for non-SP cells and have higher expression of stem cell markers as well. SP cell fraction was increased following PTX monotherapy and treatment with CYA or CYA plus PTX effectively reduced their numbers suggesting the effectiveness of combination therapy. SP fraction cells were allowed to differentiate and reanalyzed by Hoechst staining and gene expression analysis. Post differentiation, SP cells constitute 15.8% of total viable cells which decreases to 0.6% on treatment with CYA. The expression levels of P-gp efflux protein were also significantly decreased on treatment with PTX and CYA combination. MicroRNA profiling of DU145-TXR and PC3-TXR cells and prostate cancer tissue from the patients showed decreased expression of tumor suppressor miRNAs such as miR34a and miR200c. Treatment with PTX and CYA combination restored the expression of miR200c and 34a, confirming their role in modulating chemoresistance. We have shown that supplementing mitotic stabilizer drugs such as PTX with Hh-inhibitor CYA can reverse PTX chemoresistance and eliminate SP fraction in androgen independent, metastatic prostate cancer cell lines.

Comparison of rates and risk factors for development of osteoporosis and fractures after radical or partial nephrectomy.

OBJECTIVE: To examine incidence of and risk factors for development of osteoporosis and fractures in patients who underwent radical nephrectomy (RN) and partial nephrectomy (NSS), as osteoporosis is an important cause of morbidity in chronic kidney disease. METHODS: This was a retrospective review of 905 patients (mean age 57.5 years, mean follow-up 6.4 years) who underwent RN or NSS for renal tumors at 2 institutions from July 1987 to June 2007. Demographics, renal function, metabolic parameters, and history of preoperative and postoperative osteoporosis and fractures were recorded. Data were analyzed within subgroups based on treatment (RN vs NSS). Multivariate analysis was conducted to elucidate risk factors for developing osteoporosis following surgery. RESULTS: A total of 610 patients underwent RN and 295 underwent NSS. Tumor size (cm) was significantly larger for RN (RN 7.0 vs NSS 3.7, P<.0001). No significant differences were noted with respect to demographic factors and preoperative osteoporosis (RN 8.7% vs NSS 9.5%, P=.785) and fractures (RN 1.7% vs NSS 0.7%, P=.382). Postoperatively, significantly less osteoporosis (NSS 12.5% vs RN 22.6%, P<.001) and fewer fractures (NSS 4.4% vs RN 9.8%, P=.007) developed in the NSS cohort. MVA demonstrated female (OR 1.85, P=.001), Caucasian (OR 2.33, P<.0001), preoperative eGFR<60 mL/min/1.73 m2, (OR=3.02, P<.0001), preoperative metabolic acidosis (OR=4.22, P=.0006), and RN (OR 2.59, P<.0001) were risk factors for developing osteoporosis. CONCLUSIONS: Patients undergoing RN had a significantly higher incidence of osteoporosis and fractures compared with a well-matched cohort of patients who underwent NSS. In addition to RN, female gender, Caucasian background, preoperative eGFR<60, and preoperative metabolic acidosis were associated with developing osteoporosis.

Second prize: Recurrence rates after percutaneous and laparoscopic renal cryoablation of small renal masses: does the approach make a difference?

BACKGROUND AND PURPOSE: As radiologic detection of small renal masses increases, patients are increasingly offered percutaneous renal cryoablation (PRC) or transperitoneal laparoscopic renal cryoablation (TLRC). This multicenter experience compares these approaches. PATIENTS AND METHODS: Between September 1998 and May 2010, review of our PRC and TLRC experience was performed. Patients with ≥ 12-month follow-up were included for analysis. Post-treatment surveillance consisted of laboratory studies and imaging at regular intervals. Treatment failure was considered if persistent mass enhancement or interval tumor growth was radiographically evident. Repeated biopsy and re-treatment were recommended in the event of recurrence. RESULTS: Sixty-one patients underwent PRC and 84 patients underwent TLRC. No significant differences were noted with respect to demographic factors. Mean tumor size was 2.7 ± 1.1 cm (PRC) and 2.5 ± 0.8 (TLRC) cm (P = 0.090). Mean follow-up was 31.0 ± 15.9 months (PRC) and 42.3 ± 21.2 (TLRC) months (P = 0.008), with local tumor recurrence noted in 10/61 (16.4%) PRC and 5/84 (5.9%) TLRC (P = 0.042). For PRC, disease-free survival (DFS) and overall survival (OS) were 93.7% and 88.9%, respectively, with four patients having evidence of disease at last follow-up. DFS and OS were 91.7% and 89.3% for TLRC, with seven patients having evidence of disease at last follow-up. DFS (P = 0.654) and OS (P = 0.939) were similar. CONCLUSIONS: In this multicenter study of well-matched cohorts, PRC had higher primary treatment failure rates than TLRC. While no differences were noted between DFS and OS, analysis is limited by intermediate follow-up. Further study is necessary to discern reasons for the higher recurrence rates in PRC and to determine what long-term consequences exist.