Barry B. McGuire

Update on the Diagnosis and Management of Renal Angiomyolipoma

PURPOSEnAdvances in minimally invasive therapies and novel targeted chemotherapeutics have provided a breadth of options for the management ofxa0renal masses. Management of renal angiomyolipoma has not been reviewed in a comprehensive fashion in more than a decade. We provide an updated review of the current diagnosis and management strategies for renal angiomyolipoma.nnnMATERIALS AND METHODSnWe conducted a PubMed(®) search of all available literature for renal or kidney angiomyolipoma. Further sources were identified in the reference lists of identified articles. We specifically reviewed case series of partial nephrectomy, selective arterial embolization and ablative therapies as well as trials of mTOR inhibitors for angiomyolipoma from 1999 to 2014.nnnRESULTSnRenal angiomyolipoma is an uncommon benign renal tumor. Although associated with tuberous sclerosis complex, these tumors occur sporadically. Risk of life threatening hemorrhage is the main clinical concern. Due to the fat content, angiomyolipomas are generally readily identifiable on computerized tomography and magnetic resonance imaging. However, fat poor angiomyolipoma can present a diagnostic challenge. Novel research suggests that various strategies using magnetic resonance imaging, including chemical shift magnetic resonance imaging, have the potential to differentiate fat poor angiomyolipoma from renal cell carcinoma. Active surveillance is the accepted management for small asymptomatic masses. Generally, symptomatic masses and masses greater than 4 cm should be treated. However, other relative indications may apply. Options for treatment have traditionally included radical and partial nephrectomy, selective arterial embolization and ablative therapies, including cryoablation and radio frequency ablation, all of which we review and update. We also review recent advances in the medical treatment of patients with tuberous sclerosis complex associated angiomyolipomas with mTOR inhibitors. Specifically trials of everolimus for patients with tuberous sclerosis complex suggest that this agent may be safe and effective in treating angiomyolipoma tumor burden. A schema for the suggested management of renal angiomyolipoma is provided.nnnCONCLUSIONSnAppropriately selected cases of renal angiomyolipoma can be managed by active surveillance. For those patients requiring treatment nephron sparing approaches, including partial nephrectomy and selective arterial embolization, are preferred options. For those with tuberous sclerosis complex mTOR inhibitors may represent a viable approach to control tumor burden while conserving renal parenchyma.

Delay of Surgery in Men With Low Risk Prostate Cancer

PURPOSEnTreatment options for patients with low risk prostate cancer include radical prostatectomy, radiation therapy, and active surveillance. Among patients treated with radical prostatectomy, prior studies have demonstrated significantly higher biochemical progression rates with surgical delays of 6 months or greater. We determined the impact of surgical delay on radical prostatectomy outcomes specifically in low risk patients.nnnMATERIALS AND METHODSnFrom our radical prostatectomy database we identified men who fulfilled the DAmico low risk criteria (clinical stage T1c/T2a, prostate specific antigen less than 10 ng/ml, and biopsy Gleason 6 or less). Pathological tumor features and biochemical progression rates were compared between men with and without surgical delay. We used Cox proportional hazards models to examine predictors of biochemical progression.nnnRESULTSnOf 1,111 men who fulfilled the DAmico low risk criteria, those with a surgical delay of 6 months or more were significantly older, had a higher proportion of African American men, and a lower proportion of clinical stage T2a (vs T1). A surgical delay of 6 months or more was associated with a greater risk of high grade disease at prostatectomy (p = 0.001) and biochemical progression (p = 0.04). The progression-free survival rate was significantly lower among men with a surgical delay. On multivariate analysis with prostate specific antigen and clinical stage, surgical delays of 6 months or more were significantly and independently associated with time to biochemical progression.nnnCONCLUSIONSnIn men who met the DAmico low risk criteria, a surgical delay of 6 months or more was associated with significantly worse radical prostatectomy outcomes, including more pathology upgrading and a higher rate of biochemical progression. Low risk patients choosing to defer initial definitive therapy should be counseled regarding the possibility of worse treatment outcomes at a later date.

National Multi-Institutional Comparison of 30-Day Postoperative Complication and Readmission Rates Between Open Retropubic Radical Prostatectomy and Robot-Assisted Laparoscopic Prostatectomy Using NSQIP

BACKGROUNDnMany American hospitals will soon face readmission penalties deducted from Medicare reimbursements, which will place further scrutiny on techniques that may offer reduced postoperative morbidity. We aimed to perform the first multi-institutional study using the National Surgical Quality Improvement Program (NSQIP) database, to compare predictors of readmission within cohorts of open radical retropubic prostatectomy (RRP) and robot-assisted laparoscopic radical prostatectomy (RALRP) in a contemporary nationwide series of radical prostatectomy.nnnMETHODSnAll patients who underwent radical prostatectomy in 2011 were identified in the NSQIP database using procedural codes. As no patients in the analysis underwent LRP, patients were grouped as RRP or RALRP for analysis. Perioperative variables were analyzed using chi-squared and Students t-tests as appropriate. Multiple logistic regression was used to identify readmission risk factors.nnnRESULTSnOf 5471 patient cases analyzed, 4374 (79.9%) and 1097 (20.1%) underwent RALRP and RRP, respectively. RRP and RALRP cohorts experienced different readmission rates (5.47% vs 3.48%, respectively; p=0.002). In addition, RRP experienced a higher rate of overall complications than RALRP (23.25% vs 5.62%, respectively; p<0.001), but not higher rates of reoperation (1.09% vs 0.96%, respectively; p=0.689). Overall predictors of readmission included operative time, dyspnea, and RRP or RALRP procedure type. Current smoking and patient age were predictive of readmission for RRP only, while dyspnea was predictive of readmission following RALRP only.nnnCONCLUSIONnThis is the first multi-institutional retrospective study that examines readmission rates and procedural intracohort predictors of readmission for RRP in the contemporary United States. We report a significant difference in postoperative complication and readmission rates in RRP compared with RALRP. Further prospective analysis is warranted.

Personalized Prostate Specific Antigen Testing Using Genetic Variants May Reduce Unnecessary Prostate Biopsies

PURPOSEnRecent studies have identified genetic variants associated with increased serum prostate specific antigen concentrations and prostate cancer risk, raising the possibility of diagnostic bias. By correcting for the effects of these variants on prostate specific antigen, it may be possible to create a personalized prostate specific antigen cutoff to more accurately identify individuals for whom biopsy is recommended. Therefore, we determined how many men would continue to meet common biopsy criteria after genetic correction of their measured prostate specific antigen concentrations.nnnMATERIALS AND METHODSnThe genotypes of 4 single nucleotide polymorphisms previously associated with serum prostate specific antigen levels (rs2736098, rs10788160, rs11067228 and rs17632542) were determined in 964 healthy Caucasian volunteers without prostate cancer. Genetic correction of prostate specific antigen was performed by dividing an individuals prostate specific antigen value by his combined genetic risk. Analyses were used to compare the percentage of men who would meet commonly used biopsy thresholds (2.5 ng/ml or greater, or 4.0 ng/ml or greater) before and after genetic correction.nnnRESULTSnGenetic correction of serum prostate specific antigen results was associated with a significantly decreased percentage of men meeting biopsy thresholds. Genetic correction could lead to a 15% or 20% relative reduction in the total number of biopsies using a biopsy threshold of 2.5 ng/ml or greater, or 4.0 ng/ml or greater, respectively. In addition, genetic correction could result in an 18% to 22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses.nnnCONCLUSIONSnOur results suggest that 4 single nucleotide polymorphisms can be used to adjust a mans measured prostate specific antigen concentration and potentially delay or prevent unnecessary prostate biopsies in Caucasian men.

Prostate cancer diagnosis is associated with an increased risk of erectile dysfunction after prostate biopsy.

There have been several studies that have suggested there may be a relationship between prostate biopsy and erectile function and LUTS. Previous studies have suggested a specific association between the type of local anaesthesia administered and/or the number of biopsies performed. Other studies have suggested an exacerbation of LUTS after prostate biopsy. The present study identifies a positive cancer diagnosis as a novel characteristic that may explain a relationship between biopsy and worsening erectile function.

Evaluation of viability and proliferative activity of human urothelial cells cultured onto xenogenic tissue-engineered extracellular matrices.

OBJECTIVESnTo evaluate the viability and proliferative activity of human urothelial cells (HUCs) cultured on tissue-engineered extracellular matrix scaffolds and to assess the potential of extracellular matrixes to support the growth of HUCs in their expected in vivo urine environment.nnnMETHODSnHUCs were obtained by bladder biopsy and cultured onto the luminal and abluminal surfaces of decellularized porcine small intestinal submucosa (SIS) and porcine urinary bladder matrix (UBM). In addition, HUCs were cultured in optimal in vitro growth conditions and in their expected in vivo urine environment. The attachment, viability, and proliferative activity of HUCs were evaluated and compared using quantitative viability indicators and fluorescent markers for intracellular esterase activity and plasma membrane integrity.nnnRESULTSnThe luminal and abluminal surfaces of the UBM demonstrated significantly greater HUC viability and proliferative activity compared with the luminal and abluminal surfaces of the SIS grafts (P < .0001). Culture of HUCs in a simulated in vivo urine environment significantly affected cell viability (P < .0001). Proliferative activity was immeasurable on cell-seeded scaffolds that were cultured in a urine environment after 48 hours of growth (P < .0001).nnnCONCLUSIONSnThis is the first comparative report of UBM and SIS. Our results have demonstrated that UBM has significantly greater regenerative potential for HUCs compared with SIS. However, the perceived potential for extracellular matrixes in reconstructive urology might be limited by their inability to induce urothelial regeneration in a urine environment.

Outcomes in patients with Gleason score 8–10 prostate cancer: relation to preoperative PSA level

Study Type – Therapy (case series)

Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases

Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤6, 7, ≥8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (ORxa0=xa00.77; 95xa0% CI 0.69–0.87) and high-grade disease (ORxa0=xa00.77; 95xa0% CI 0.68–0.86) in European men. Similar associations with aggressive (ORxa0=xa00.72; 95xa0% CI 0.58–0.89) and high-grade disease (ORxa0=xa00.69; 95xa0% CI 0.54–0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (<4.0xa0ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness.

Sexual function outcomes following fracture of the penis.

INTRODUCTIONnFracture of the penis is a rare urological emergency which occurs as a result of abrupt trauma to an erect penis. There is paucity of data regarding long-term sexual function or erectile potency following fracture of the penis. The aim of this study is to objectively assess the overall sexual function following fracture of the penis.nnnMETHODSnA retrospective analysis of 21 penile fractures was performed. A voluntary telephone questionnaire was performed to assess long term outcomes using three validated questionnaires-the Erection Hardness Grading Scale, the International Index of Erectile Function (IIEF-5) and the Brief Male Sexual Function inventory (BMSFI).nnnRESULTSnThe mean age was 33.1 years (range: 19-63). The median follow up was 46 months (range: 3-144). All fractures were a result of sexual misadventure and all were surgically repaired. There were two concomitant urethral injuries. Seventeen patients were contactable. Fourteen patients demonstrated no evidence of erectile dysfunction (ED) (IIEF-5>22), 1 patient reported symptoms of mild ED (IIEF-5, 17-21) and one patient reported mild to moderate ED (IIEF-5, 12-16). No patients reported insufficient erection for penetration (EHGS: 1 or 2). Regarding the overall BMSFI, 13 (83%) patients were mostly satisfied or very satisfied with their sex life within the previous month.nnnCONCLUSIONnIn a small surgical series of men with penile fracture managed within a short time frame from presentation, we demonstrate erectile potency is maintained. Long-term overall sexual satisfaction is promising.

The effect of surgical duration of transurethral resection of bladder tumors on postoperative complications: An analysis of ACS NSQIP data.

INTRODUCTIONnTransurethral resection of bladder tumor (TURBT) is a common procedure used in the diagnosis and treatment of bladder cancer. Despite how often it is performed, not much is known about the risk factors for complications. Traditional surgery has an increase in morbidity and mortality with increasing operative duration. We assess the effect of operative duration on TURBT complications.nnnMETHODSnThe years 2006 to 2012 of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) were queried for patients undergoing TURBT. We separated patients into 4 groups based on operative time: 0 to 30 minutes, 30.1 to 60 minutes, 60.1 to 90 minutes, and greater than 90 minutes. Standard statistical analysis including multivariate regression was performed to determine predictors of complications.nnnRESULTSnA total of 10,599 TURBTs were included in our analysis. The overall complication rate for TURBT was 5.8% and there was an increase in the rate of complications seen as operative duration increased, which remained after controlling for age, comorbidities, tumor size, and American Society of Anesthesiology classification. Increased operative duration was associated with a greater risk of postoperative urinary tract infection, sepsis or septic shock, pulmonary embolism/deep venous thrombosis, reintubation or failure to wean, myocardial infarction, and death. Larger tumors were related to an increased odds of requiring blood transfusions.nnnCONCLUSIONSnUsing a contemporary multicenter cohort of TURBTs from the ACS NSQIP database, we demonstrate that increased operative duration is associated with serious postoperative complications. This association was found to persist even after adjusting for patient age, comorbidities, tumor size, and functional status.