Greg Hruby

Clinical Outcomes After Radical Prostatectomy in Diabetic Patients Treated With Metformin

OBJECTIVES To investigate the relationship between diabetes and metformin use with outcomes after radical prostatectomy (RP) for clinically localized cancer. METHODS A total of 112 diabetic metformin users and 98 diabetic non-metformin users treated with RP from 1990 to 2009 were identified. Nondiabetic controls were match using their 5-year risk of biochemical recurrence (BCR) as calculated by the preoperative Kattan nomogram. RESULTS A total of 616 patients were evaluated in this study. There was no significant difference between nondiabetic and diabetic patients, including metformin users, with respect to age, clinical stage, preoperative prostate-specific antigen (PSA) score, pathologic Gleason score, and pathologic stage. Diabetic patients, including metformin users, were more likely to be of African American or Hispanic background than were nondiabetic controls (P = .001). The estimated 5-year BCR-free survival was 75.0% for nondiabetic patients, compared with 66.1% for metformin users and 59.3% for diabetic non-metformin users (P = .004). In multivariate analysis, metformin use was not significantly associated with risk of BCR (HR = 0.94; 95% CI = 0.6-1.5, P = .817). However, being diabetic, regardless of metformin use, resulted in a 55% increase in risk of BCR (HR = 1.55; 95% CI = 1.03-2.33, P = .034). CONCLUSIONS Diabetes, regardless of metformin use, was significantly associated with an increased likelihood of BCR after RP. Metformin use did not prove to be of any benefit. These observations underscore the importance for further studies evaluating the metabolic pathways that affect prostate cancer biology.

Skin to Stone Distance Is an Independent Predictor of Stone-Free Status Following Shockwave Lithotripsy

INTRODUCTION In recent years several new parameters such as Hounsefield unit density and skin to stone distance (SSD) have been determined to correlate with successful extracorporeal shockwave lithotripsy (SWL). SSD has been shown to independently predict successful SWL for lower pole calculi. The objective of this study was to determine which stone characteristics on noncontrast computed tomography (NCCT), including SSD, independently predict for SWL success regardless of stone location within the kidney. MATERIALS AND METHODS A retrospective review of all 1282 SWL procedures between 2004 and 2007 at a single institution revealed 83 patients meeting inclusion criteria for current study. All patients were treated using a single electromagnetic lithotriptor (DoLi 50; Dornier Medical Systems, Marrieta, GA) with a single technician. Stone-free (SF) status was determined by NCCT or abdominal plain film radiographs at 6 weeks post-SWL. Logistic regression analysis was computed to assess SF rates using SSD, stone size, location, and Hounsefield unit density as predictors. RESULT Of the 83 patients, 51 were SF and 32 had residual stones at a mean follow-up of 2.3 months. The mean SSD in the SF group was 83.3 +/- 21.9 mm in comparison to those in the residual stone group who had a mean SSD of 107.7 +/- 28.9 mm (p < or = 0.05). Multivariate logistic regression analysis revealed that SSD was the only significant independent predictor of treatment outcome. CONCLUSION SSD is an easily measured parameter on NCCT that independently correlates with SWL efficacy in treating stones in all locations.

Pathological outcome and biochemical recurrence‐free survival after radical prostatectomy in African‐American, Afro‐Caribbean (Jamaican) and Caucasian‐American men: an international comparison

Whats known on the subject? and What does the study add?

Effect of statin use on biochemical outcome following radical prostatectomy: EFFECT OF STATIN USE ON BIOCHEMICAL OUTCOME FOLLOWING RADICAL PROSTATECTOMY

Study Type – Prognosis (retrospective cohort)

Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer.

Purpose The analysis of exosome/microvesicle (extracellular vesicles (EVs)) and the RNA packaged within them (exoRNA) has the potential to provide a non-invasive platform to detect and monitor disease related gene expression potentially in lieu of more invasive procedures such as biopsy. However, few studies have tested the diagnostic potential of EV analysis in humans. Experimental Design The ability of EV analysis to accurately reflect prostate tissue mRNA expression was examined by comparing urinary EV TMPRSS2:ERG exoRNA from pre-radical prostatectomy (RP) patients versus corresponding RP tissue in 21 patients. To examine the differential expression of TMPRSS2:ERG across patient groups a random urine sample was taken without prostate massage from a cohort of 207 men including prostate biopsy negative (Bx Neg, n = 39), prostate biopsy positive (Bx Pos, n = 47), post-radical prostatectomy (post-RP, n = 37), un-biopsied healthy age-matched men (No Bx, n = 44), and young male controls (Cont, n = 40). The use of EVs was also examined as a potential platform to non-invasively differentiate Bx Pos versus Bx Neg patients via the detection of known prostate cancer genes TMPRSS2:ERG, BIRC5, ERG, PCA3 and TMPRSS2. Results In this technical pilot study urinary EVs had a sensitivity: 81% (13/16), specificity: 80% (4/5) and an overall accuracy: 81% (17/21) for non-invasive detection of TMPRSS2:ERG versus RP tissue. The rate of TMPRSS2:ERG exoRNA detection was found to increase with age and the expression level correlated with Bx Pos status. Receiver operator characteristic analyses demonstrated that various cancer-related genes could differentiate Bx Pos from Bx Neg patients using exoRNA isolated from urinary EVs: BIRC5 (AUC 0.674 (CI:0.560–0.788), ERG (AUC 0.785 (CI:0.680–0.890), PCA3 (AUC 0.681 (CI:0.567–0.795), TMPRSS2:ERG (AUC 0.744 (CI:0.600–0.888), and TMPRSS2 (AUC 0.637 (CI:0.519–0.754). Conclusion This pilot study suggests that urinary EVs have the potential to be used as a platform to non-invasively differentiate patients with prostate cancer with very good accuracy. Larger studies are needed to confirm the potential for clinical utility.

Single Institutional Experience with Nephron-sparing Surgery for Pathologic Stage T3bNxM0 Renal Cell Carcinoma Confined to the Renal Vein

OBJECTIVE To assess our institutions experience with the management of pathologic stage T3bNxM0 renal cell carcinoma with tumor thrombus confined to the renal vein treated with nephron-sparing surgery (NSS). METHODS Of the 492 patients who have undergone NSS at Columbia University from 1998 to 2009, 8 patients were found to have stage T3bNxM0 renal cell carcinoma (RCC) on final pathology. Records were reviewed for indication for NSS, imaging studies, perioperative management, surgical details, pathology, and both functional and disease-specific outcomes. Postoperative renal function was estimated by most recent glomerular filtration rate using Modification of Diet in Renal Disease formula. Recurrence of RCC was monitored using serial axial imaging. RESULTS The 8 patients were presumed to be clinical stage T1aN0M0 RCC before surgery; however, tumor thrombus was identified in the renal vein intraoperatively and on final pathology in 4, and 4 cases, respectively, corresponding to stage T3bNxM0 RCC by current American Joint Committee on Cancer-Tumor-Necrosis-Metastasis 2002 criteria. After a median follow-up of 19.8 months, the patients experienced a mean decrease in estimated glomerular filtration rate of 27.1%. One patient developed new-onset renal failure, defined as an estimated glomerular filtration rate below 30 mL/min/1.73 m(2). Clean surgical margins were obtained in 7 patients. Carcinoma was identified at the parenchymal margin in 1 patient. No patients have evidence of recurrence of RCC by serial axial imaging. CONCLUSIONS NSS does not seem to have had a negative impact on a small series of patients with pathologic stage T3bNxM0 RCC limited to the renal vein and may be a feasible option when the clinical situation indicates a need for preservation of renal function.

Heparin prophylaxis and the risk of venous thromboembolism after robotic‐assisted laparoscopic prostatectomy

Study Type – Therapy (case series)

Evaluation of a protective laser sheath for application in flexible ureteroscopy.

OBJECTIVES Despite the obvious utility of the holmium laser, laser fibers frequently damage flexible ureteroscope components, such as the working channel, flexible component cable system, and fiber optical systems during routine ureteroscopic procedures. As such, we investigated the effects of the use of a flexible protective sheath on ureteroscope operation and its ability to protect ureteroscopes from laser fiber damage. METHODS The effects of insertion of the FlexGuard sheath into the working channel on endoscope deflection and irrigant flow rate were documented. Additionally, the force required to advance the laser fiber through a fully deflected endoscope, as well as the amount of laser energy required to penetrate the FlexGuard sheath, were assessed using two different ureteroscopes. RESULTS The FlexGuard sheath was easily inserted through the maximally deflected ureteroscopes. The presence of the laser sheath and a laser fiber in the working channel decreased the maximum deflection angle of the ureteroscopes by a mean of 7 degrees (from 73 degrees to 66 degrees). FlexGuard sheath insertion into the working channel also significantly diminished irrigant flow rates, from 0.55 mL/sec to 0.02 mL/sec, at an irrigation pressure of 100 cm H(2)O. The FlexGuard sheath reduced the amount of maximum force required to insert the laser fiber through each ureteroscope from 0.8 N to 0.2 N. The FlexGuard sheath was unable to protect the ureteroscope from laser energy damage. CONCLUSION The FlexGuard laser sheath significantly reduced the amount of force required to insert the laser fiber through the working channel. This reduction in force may have be protective against mechanical damage caused by laser fiber insertion. However, deployment of the sheath significantly diminished the rate of irrigant flow and the maximal deflection of the two ureteroscopes tested. Also, the sheath does not protect the ureteroscope from damage caused by laser energy. In each case the urologist will need to determine if the mechanical protective value of the sheath outweighs the negative impact on flow and deflection.

Synchronous cryoablation of multiple renal lesions: short-term follow-up of patient outcomes.

OBJECTIVES To report on various perioperative and short-term clinical outcomes of 7 patients who underwent cryoablation of multiple renal lesions during the same operative setting. Cryotherapy is the most well studied minimally invasive ablative technique for the treatment of renal tumors. METHODS A retrospective analysis of our institutional renal cryotherapy database yielded a total of 7 patients who underwent synchronous cryoablation of > 1 renal lesion between August 2005 and May 2007. RESULTS Mean patient age was 63.9 years, and median follow-up was 23.3 months (range 7-28 months). Five patients had ablation of 2 renal lesions, 1 had 3 lesions, and 1 had 4 lesions. The mean greatest diameter of any single lesion was 2.0 cm (range 0.7-7.5 cm). Mean preoperative serum creatinine was 1.5 mg/dL (range 0.7-3.6 mg/dL), which increased to a mean of 1.7 mg/dL (range 0.7-3.6) at last follow-up. Mean estimated blood loss was 138 mL (range 38-300 mL). There were 2 complications--ureteral stenting because of postoperative renal colic, and blood transfusion for decreased hematocrit. Of the 17 lesions, 7 were found to be conventional renal cell carcinoma, 4 papillary, 2 myelolipoma, and 1 oncocytoma (unavailable for 3 lesions). Mean length of hospital stay was 2.3 days (range 1-6 days). At last follow-up, computed tomography scanning demonstrated no recurrences in any patient. CONCLUSIONS Cryoablation of multiple renal lesions at one setting may be successfully performed with few complications, with minimal short-term loss of renal function as estimated by serum creatinine, and with short-term evidence of tumor destruction.

Findings of routine apical margin biopsy during robot-assisted radical prostatectomy.

INTRODUCTION Intraoperative biopsy of the apical margin during radical prostatectomy has been recommended as a way to reduce the positive margin rate at this location. However, the enhanced visibility of the apex during robot-assisted radical prostatectomy (RARP) may obviate this need, allowing for the preservation of maximal urethral length. We assessed pathologic findings of routine apical margin biopsy intraoperative frozen section (IFS) during RARP. PATIENTS AND METHODS The Columbia University Robotic Database was retrospectively reviewed to identify men who underwent RARP with biopsy of the apical soft tissue (urethroprostatic junction). Both IFS and permanent section samples were analyzed. The clinical characteristics associated with IFS and permanent section histological findings were assessed. RESULTS In total, 335 men underwent RARP with apical biopsy from December 2007 to August 2011. Of these, 329 had IFS available for analysis. Median age and prostate-specific antigen level were 60 years (range, 42-78 years) and 5.2 ng/mL (interquartile range, 4.1-6.9 ng/mL), respectively. Of the 329 apical IFS cases, cancer was detected in 9 patients (2.7%), benign prostatic glands in 135 (41%), and nonprostatic tissue in 185 (56.3%). On permanent section, cancer was seen in 9 patients (2.7%), benign prostatic glands in 125 (38%), and nonprostatic tissue in 195 (59.3%). False-positive and false-negative rates of detecting cancer on IFS were 33% (3/9) and 1% (3/320), respectively. The overall positive surgical margin rate was 11%. CONCLUSIONS Cancer is rarely detected by IFS analysis of routine biopsy of the apical margin during RARP. Although routine IFS may not be beneficial for all patients, selective utilization of IFS may be useful in directing apical dissection in men with apical tumors, allowing for the preservation of maximal urethral length.