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.

The natural history of clinically complete responders to neoadjuvant chemotherapy for urothelial carcinoma of the bladder.

PURPOSE: We describe the clinical course of patients who achieved cT0 status after neoadjuvant chemotherapy for muscle invasive bladder cancer. There is no established treatment paradigm for these patients. MATERIALS AND METHODS: We retrospectively reviewed the records of 109 patients with muscle invasive bladder cancer (T2 or greater urothelial carcinoma of the bladder) who underwent platinum based neoadjuvant chemotherapy at our institution from 1988 to 2012. Post-chemotherapy assessment of the response included cytology, cystoscopy with biopsy and cross-sectional imaging. RESULTS: Of 109 patients 32 (29.4%) achieved cT0 status after neoadjuvant chemotherapy. Mean ± SD age of the cohort was 68.3 ± 9.6 years. Of the patients 21 received MVAC, 8 received gemcitabine and cisplatin, and 3 received another regimen. Seven complete responders elected immediate radical cystectomy after the completion of neoadjuvant chemotherapy. Of 25 patients who refused radical cystectomy after achieving cT0 status 7 experienced relapse after the completion of neoadjuvant chemotherapy and proceeded to radical cystectomy. The remaining 18 patients (72%) retained the bladder, including 6 (18.8% of the cohort) in whom nonmuscle invasive relapses were managed conservatively and 12 (37.5%) with no recurrence. In the 25 patients who elected bladder preservation after achieving cT0 status following neoadjuvant chemotherapy 5-year cancer specific survival was 88%. CONCLUSIONS: With proper counseling and identification of treatment goals patients with cT0 after neoadjuvant chemotherapy for muscle invasive bladder cancer may have the option to retain the bladder with durable survival. Larger studies are needed to identify possible predictors of response on the clinical, pathological and molecular levels.

Diagnostic radiation exposure during surveillance in patients with pT1a renal cell carcinoma.

OBJECTIVE: To determine the pattern of postoperative radiographic surveillance in patients with pT1a renal cell carcinoma (RCC) at a tertiary care hospital. METHODS: An institutionally approved urologic oncology database was used to retrospectively identify patients who underwent partial or radical nephrectomy for pT1a RCC from 1990 to 2010 at a tertiary care center. Baseline characteristics were reviewed, and postoperative imaging for the indication of RCC surveillance was recorded. Radiation exposure was calculated using the effective dose according to imaging modality. Relative risks of the development of solid malignancies and leukemia were calculated from the dose of radiation exposure. RCC recurrence, defined as radiologic evidence of local recurrence or distant metastases, was noted. RESULTS: A total of 1708 patients had undergone partial or radical nephrectomy for a renal mass. Of these, 315 patients had pT1a RCC with postsurgical follow-up, and 252 (80%) of these patients were exposed to ionizing radiation during postoperative surveillance. Mean radiation doses in years 1, 2 to 5, and ≥6 after surgery were 11.4, 47.0, and 13.8 mSv, respectively. Relative risks of radiation-induced solid cancers and leukemia were 1.05 and 1.12, respectively. There were 8 (2.5%) total recurrences. CONCLUSION: During the past 20 years, 80% of patients undergoing surgery for pT1a RCC were monitored with radiation-based imaging during postoperative surveillance. Given the low rate of cancer recurrence in this population, expanded efforts in counseling physicians regarding the risk of ionizing radiation in imaging should be encouraged.

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.

The effect of fibrin clot inhibitors on the immunomodulatory efficacy of Bacillus Calmette-Guérin therapy for non-muscle-invasive bladder cancer.

OBJECTIVE: To determine if there is a difference in clinical outcomes among non-muscle-invasive bladder cancer patients taking fibrin clot-inhibiting (FCI) medications (aspirin, clopidogrel, or warfarin) while receiving Bacillus Calmette-Guérin (BCG) therapy compared with their counterparts not taking anticoagulation. MATERIALS AND METHODS: Our Investigational Review Board-approved database was queried for patients who received an induction course of BCG from 2001 to 2011. The analysis included 224 patients with a minimum of 3 months of follow-up. Recurrence-free survival (RFS), cystectomy-free survival, overall survival, and disease-specific survival were analyzed using the Kaplan-Meier method stratified by FCI status. Logistic regression was used to predict the initial response rate to BCG and progression by FCI status. RESULTS: Of the 224 patients analyzed, 68, 19, and 23 patients were taking aspirin, clopidogrel and warfarin, respectively, at BCG induction. No specific FCI was associated with differences in cystectomy-free survival, overall survival, disease-specific survival, or the likelihood of progression at recurrence. Neither warfarin nor clopidogrel affected RFS. Patients taking aspirin trended toward increased RFS, although this was not statistically significant (P = .058). Multivariate analysis showed aspirin use was associated with an increased initial response to BCG (odds ratio, 2.41; P = .031) CONCLUSION: Contrary to the postulated inhibitory molecular effect of FCI on BCG-binding activity, this study did not substantiate a significant impact on BCG efficacy of the concomitant use of these medications during BCG induction. The observation that aspirin use potentiates an increased initial response to BCG may warrant further analysis.

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

OBJECTIVE: To compare pathological and biochemical outcomes of radical prostatectomy (RP) among African-American (AA), Afro-Caribbean (AC; Jamaican) and Caucasian-American (CA) men using an international cohort of patients who underwent RP in the USA and Jamaica. MATERIALS AND METHODS: A retrospective review was performed of men who underwent RP for clinically organ-confined (OC) prostate cancer between 2000 and 2011 at Columbia University Medical Center (New York, USA) and the University Hospital of the West Indies (Kingston, Jamaica) between 2000 and 2007. Men who had received neoadjuvant or adjuvant (within 3 months) therapy were excluded. Clinicopathological variables were compared among the three groups, focusing on age, stage, PSA level, Gleason sum (GS) and margin status. Multivariate analysis was performed to determine the predictors of biochemical recurrence (BCR; PSA >0.2 ng/mL), and Kaplan-Meier analysis was performed to determine BCR-free survival rates in AA, AC and CA men. RESULTS: A total of 483 men underwent RP for clinically OC disease (CM, n = 309, AA, n = 93 and AC, n = 81). The mean patient age was 59 years, with AA men being younger than CA men (58 vs 60 years, P< 0.05). The mean (range) follow-up was 49 (13-133) months with no significant difference among the groups. The men in the AC cohort had a higher mean PSA level than AA and CA men (8.8 vs 6.2 and 5.0 ng/mL, respectively, P< 0.05) and more clinical GS ≥7 (44%) tumours than AA (8%) and CA men (0%; P< 0.01). On multivariate analysis, controlling for stage, grade, PSA level and margins, AA and AC race were independent predictors of BCR. AA and AC men had significantly lower 5-year BCR-free survival (76 and 74%, respectively) than CA men (98% [P < 0.001]). CONCLUSIONS: This international comparison of clinicopathological outcomes in AA, AC and CA men undergoing RP shows that AA and AC men present similarly with more aggressive disease features than CA men and have lower 5-year BCR-free survival. Both AA and AC race are significant predictors of BCR, independently of stage, grade, PSA level and margin status. Further research is needed to elucidate and correct the mechanisms behind the observed difference in outcome among these populations.

Is there a difference in laterality during robot-assisted radical prostatectomy? Assessment of lymph node yield and neurovascular bundle dissection.

BACKGROUND AND PURPOSE: The da Vinci Surgical System (dVSS) has been reported to eliminate innate hand dominance of the surgeon. There are no studies to date, however, that specifically address whether the dVSS has its own inherent "handedness" resulting from the fixed left-right preference of specific instrument docking and assistant positioning. We identified the pelvic lymph node (LN) and neurovascular bundle (NVB) dissections as well as positive surgical margin rates as procedure points during robot-assisted radical prostatectomy (RARP) that could be influenced by laterality and sought to illustrate left-right consistency. PATIENTS AND METHODS: Patients who underwent RARP by a single right-handed surgeon (KKB) between 2008 and 2010 were identified. Surgeon instrument preference and port placement were consistent across all cases. Pathologic LN yield was stratified by the intended limits of dissection (limited or extended) and laterality. In addition, fascial widths (FW) were prospectively measured for 93 consecutive patients, a narrower FW indicating a more precise intended NVB dissection. The pathologists were blinded to intended dissections. RESULTS: A total of 340 limited, 11 bilateral extended, 11 right extended, and 5 left extended LN dissections were performed. For patients undergoing limited LN dissection, the mean LN yield was greater on the right compared with the left (3.26 vs 2.76, P=0.010). This difference was not seen in the extended LN dissection (P=0.96). Average FW was narrower on the right surgical margin compared with the left (1.99 vs 2.64 mm, P<0.001). CONCLUSIONS: Our findings suggest that a greater number of LNs and a closer NVB dissection are achieved on the right compared with the left using the dVSS during RARP. This can be attributed to surgeon handedness, robotic instrument laterality, or assistant instrument laterality. Surgeon awareness of these potential differences is important for the preoperative planning before RARP.

Effect of statin use on biochemical outcome following radical prostatectomy.

OBJECTIVE: •To determine the relationship between statin use and biochemical recurrence (BCR) following radical prostatectomy (RP). PATIENTS AND METHODS: •A retrospective analysis was performed on 3198 RP patients between 1990 and 2008. •Exclusion criteria were neo-adjuvant or adjuvant therapy, follow-up <2 years, and insufficient pathological or prostate-specific antigen (PSA) data. •Statin use was determined from the patient's record. Clinical and pathological variables were compared between statin users and non-users. •Kaplan-Meier and multivariate Cox regression analyses were performed to determine the effect of statin use on BCR. RESULTS: •A total of 1261 patients fit criteria for analysis. There were 281 (22%) statin users. Mean age was 60 years and median follow-up was 36 months (mean 43 months). •Statin users had a lower median preoperative PSA (6.4) compared with non-users (7.1) (P < 0.05). In all, 80% of statin users had a pathological Gleason sum ≥7 compared with 67% of non-users (P < 0.05). •On multivariate analysis, statin use was an independent predictor of BCR (hazard ratio 1.54, P < 0.05). Statin users had a lower 5-year BCR-free survival compared with non-users (75% vs 84%, P < 0.05). CONCLUSIONS: •Statin users are at an increased risk for BCR following RP. This finding may be due to the reduction in preoperative PSA potentially delaying diagnosis and/or masking aggressive disease. •Further studies are necessary to elucidate the impact of statin medications following prostate cancer therapy.

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

OBJECTIVE: • The incidence of venous thromboembolism (VTE) after robotic-assisted laparoscopic prostatectomy (RALP) in patients receiving perioperative heparin prophylaxis was compared with those who did not receive such prophylaxis. MATERIALS AND METHODS: • Between July 2007 to February 2010, a total of 307 RALPs were performed at our institution by two surgeons. A total of 187 patients operated on by surgeon 1 received perioperative heparin prophylaxis, whereas 120 patients operated on by surgeon 2 did not receive any. • All demographic, clinical and pathological data were prospectively recorded, whereas the incidence of venous thromboembolism within 30 days of the operation was retrospectively reviewed. Evaluation for potential VTE was based on clinical symptoms. RESULTS: • Cohorts were comparable with respect to PSA, clinical stage, preoperative Gleason score, body mass index, smoking status, pathological stage, path Gleason score and margin status. A total of two thromboemoblic events occurred (0.6%) within 30 days of surgery (one in each arm of the study). • Heparin prophylaxis did not influence estimated blood loss (P= 0.076) or haematocrit change from preoperative levels (P= 0.378). Length of stay was comparable between the two groups (1.4 vs 1.3 days; P= 0.159). CONCLUSION: • The incidence of thromboembolism is low after RALP, which may obviate the need for heparin prophylaxis. However, its use is safe and does not impact surgical outcomes. Larger series are needed to confirm the results obtained in the present study.

Renal function and oncologic outcomes in nephron sparing surgery for renal masses in solitary kidneys.

INTRODUCTION: With low life expectancy rates in hemodialysis patients, the preservation of renal parenchyma must be weighed against the oncological outcomes in considering partial nephrectomy (PN) in solitary kidneys. The main objective of this study was to assess the oncologic and functional outcomes after PN in patients with solitary kidneys. METHODS: A retrospective analysis of the Columbia University Medical Center Urologic Oncology database found 38 patients who underwent PN in the setting of a solitary kidney from 1988-2008. Chronic kidney disease (CKD) was defined as GFR of <60 cc/min/1.73 m(2). Kaplan-Meier analysis was used to estimate overall survival, cancer-specific survival, and local recurrence-free survival. RESULTS: The study group was followed for a median of 29 months, with a mean age of 63.2 years (range 35-83). Only one patient required postoperative long-term hemodialysis. Two out of 38 patients had a Clavien III postoperative complication. Twenty-one (55.3%) of the patients had preoperative CKD, while 29 (76%) patients had CKD postoperatively. Those who had CKD at the most recent follow-up had significantly larger tumors removed (P < 0.05). Of the 32 patients with renal cell carcinoma (RCC), 6 (18.8%) had a local recurrence at a median 32.6 months. The 5-year overall, disease-specific, and recurrence-free survival rates were 59.6, 77.5, and 45.7%, respectively. CONCLUSION: PN in the setting of a solitary kidney poses difficult challenges for surgical and clinical management. Nephron sparing surgery for the treatment of RCC is feasible with low surgical complication rates, satisfactory disease-specific survival rates, and acceptable preservation of renal function.

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.

Single institutional experience with nephron-sparing surgery for pathologic stage T3bNxM0 renal cell carcinoma confined to the renal vein.

OBJECTIVE: To assess our institution's 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.

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.

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.

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.

Office-based surveillance ureteroscopy after endoscopic treatment of transitional cell carcinoma: technique and clinical outcome.

OBJECTIVES: The reference standard treatment for transitional cell carcinoma (TCC) of the upper tract remains nephroureterectomy. However, with improvements in endoscopic technology and techniques, endoscopic ablation of upper tract TCC has become a reality for highly selected patients. We report our present technique and 16-year experience of office-based ureteroscopy for surveillance of TCC after initial endoscopic ablation. METHODS: The office and hospital records of all patients undergoing office-based anesthesia-free ureteroscopy were retrospectively reviewed. The patient characteristics, tumor characteristics, ureteroscopic technique and findings, and complications were documented. RESULTS: Ten patients with a mean age of 68.8 years were treated with endoscopic ablation of upper tract TCC. A total of 67 (range 1 to 19 per patient) surveillance ureteroscopies in the office setting were performed. Office ureteroscopy revealed seven upper tract TCC recurrences in 5 patients. A thorough ureteroscopic examination in the operating room of these patients revealed that only 1 patient had more extensive disease than was recognized during the office-based ureteroscopy. All patients tolerated office-based ureteroscopy well, and each procedure was successfully completed with minimal patient discomfort. No acute complications were noted. One patient who experienced multiple recurrences and underwent ablation of extensive ureteral TCC developed a benign ureteral stricture. CONCLUSIONS: The results of our study have shown that for the rare patient undergoing endoscopic management of upper tract TCC, office-based anesthesia-free ureteroscopic surveillance is a reasonable management strategy. The technique has been free of complications and appears to be as accurate as surveillance ureteroscopy performed in the operating room.

Pharmacologic manipulation of the porcine ureter: Acute impact of topical drugs on ureteral diameter and peristaltic activity.

BACKGROUND AND PURPOSE: Intraluminal application of pharmacologic agents for acute ureteral dilation may facilitate difficult ureteroscopy. We characterized the in-vivo effects of intraluminal application of verapamil and theophylline on ureteral peristalsis and diameter in a porcine model. MATERIALS AND METHODS: Twenty-four female domestic pigs (35-40 kg) were incorporated into the study. We deployed a giant magneto resistive (GMR) sensor and electromagnetic (EMG) electrodes laparoscopically onto the ureteral surface for simultaneous measurement of the mechanical and electrical signals of ureteral peristalsis, respectively. The ureteral-luminal diameter was measured at three levels by digital retrograde pyelography and standardized to a 10-mm laparoscope. The results were calculated as change in peristalsis and ureteral diameter from baseline during the first hour after drug injection. We tested two smooth-muscle relaxants, verapamil (2 mg/kg) and theophylline (70 mg/kg), with saline and dimethylsulfoxide (DMSO; solvent) as controls. Six pigs were studied for each of the four groups. Hydration, anesthesia, and intra-abdominal pressure were standardized. The serum concentrations of the drugs were measured to determine systemic absorption. RESULTS: During the first 10 minutes after intraluminal drug injection, theophylline caused a significant decrease in ureteral peristalsis (6.75 waves/10 minutes) compared with the control group (1.00/10 minutes; P = 0.02). This trend persisted for the next hour. However, there were no changes from baseline in ureteral width. Ureteral peristalsis and dilation remained similar after the saline and DMSO injections. Verapamil increased the diameter of the proximal ureter compared with the controls throughout the hour after drug injection. Fifteen minutes after the drug injection, the change in the ureteral diameter with verapamil was 1.38 mm (4.14F), while the control group showed a change of 0.27 mm (P = 0.03). At 1 hour, the width of the proximal ureter in the verapamil group had increased by 1.72 mm (5.16F), while the control group had changed by 0.55 mm (P = 0.03). There were no statistically significant changes in the widths of the mid or distal ureter. No ureteral dilation was observed in the other groups. CONCLUSIONS: In the porcine model, intraluminal application of pharmacologic agents produced independent effects on ureteral dilation and peristalsis. Theophylline inhibited ureteral peristalsis, and verapamil produced acute proximal-ureteral dilation. The ability to alter ureteral diameter or peristaltic activity acutely may facilitate ureteroscopy.

Precise characterization of renal parenchymal response to single and multiple cryoablation probes.

PURPOSE: We characterized the size and shape of the ablated area, and the surrounding indeterminate zone associated with renal cryolesions produced by single and multiple cryoablation probe configurations in a porcine model. MATERIALS AND METHODS: Laparoscopic cryoablation, consisting of 2, 10-minute double freeze cycles followed by a 3-minute active thaw, was performed in 18 pigs. Three groups of 6 pigs each were studied, including a single IceRod, 3 rods arranged in a triangular configuration 2 cm apart from each other and 4 rods arranged in a quadratic configuration 2 cm from each other. Cryoablated kidneys were harvested after 14 days for histopathological evaluation. RESULTS: The mean diameter of the area of complete ablation produced by a 1, 3 and 4 rod configuration 1 cm from the tip of the rod was 2.0, 4.4 and 4.9 cm, respectively. Cryolesions were elliptical with 1 cryoablation probe and in the 3 and 4 rod configurations they conformed to triangular and quadratic cross-sectional shapes, respectively. In the zone, ablation a single small focus of peri-arteriolar renal cell viability was noted less than 1 mm from the edge of the cryolesion in 1 of the 18 cryolesions. Otherwise no viable renal cells were detected. CONCLUSIONS: Multirod configurations can be used with templates to space cryoablation probes 2 cm apart from each other with reliable and complete ablation overlap between the rods. However, around larger blood vessels the ice ball must be extended to a larger margin to ensure complete tissue ablation.

Evaluation of a novel knotless self-anchoring suture material for urinary tract reconstruction.

OBJECTIVES: To evaluate a novel prototype self-anchoring suture (SAS) material that incorporates unidirectional "barbs" designed to grip and approximate tissue without the need for suture ligation for urinary tract reconstructive procedures. METHODS: The in vitro failure strength of various porcine tissue approximations with SAS was compared with the strength of similar approximations with standard ligated suture. For in vivo analysis, 3 pigs underwent laparoscopic pyeloplasty with SAS on one side and 2-0 Vicryl suture on the contralateral side. Nine pigs underwent bladder neck anastomoses (BNA) performed with SAS (n = 3) and standard ligated interrupted suturing (n = 3) or standard ligated running suturing (n = 3). The operative times were compared. One week after surgery, the integrity of each anastomosis was evaluated radiographically and histopathologically. RESULTS: The in vitro analysis revealed no statistically different (P = 0.22) failure forces between the approximations performed with SAS (13.2 +/- 2.6 N) and standard suture (14.1 +/- 3.1 N). The in vitro analysis revealed no difference in operative times for the pyeloplasties (P = 0.72) or BNA (P = 0.31). None of the 1-week postoperative radiographic studies revealed extravasation. The histopathologic analysis revealed more fibrotic reaction associated with the SAS BNA procedures (P <0.01). CONCLUSIONS: Self-anchoring suture secures tissue approximations at loads equivalent to tissue approximations with standard tied suture. Self-anchoring suture obviates the need for knot tying and provides a watertight anastomosis. With laparoscopic knot tying experience, anastomotic time with SAS and standard suture do not differ. Self-anchoring suture might induce more fibrosis. Long-term follow-up evaluation will be required before clinical application.

Comparison of mechanical and in vivo performance of new and reprocessed harmonic scalpels.

OBJECTIVES: To compare the mechanical and clinical performance of new and reprocessed harmonic scalpels (HS). METHODS: A total of 89 reprocessed and 90 new HS (laparoscopic coagulating shears with a curved blade and 5-mm-diameter shaft) were subjected to visual inspection, destructive testing, and nondestructive mechanical testing. Subsequently, new HS, randomly selected reprocessed HS, and selected reprocessed HS with known abnormalities were graded on clinical performance by 14 surgeons in a porcine model. RESULTS: Visual inspection of the HS discriminated between the new and reprocessed instruments in 11 of the 12 visual criteria (P < or = 0.02). In vitro mechanical testing revealed greater clamp arm dislodge forces for the new HS (P < 0.01) and greater midshaft temperatures for reprocessed HS (P < 0.01). Overall, 65 (73%) of 89 reprocessed and 7 (7.8%) of 90 new HS had gross abnormalities noted on inspection and mechanical evaluation (P < 0.01). The surgeons' evaluation of the instruments during in vivo testing demonstrated that the new instruments manifested significantly greater hemostatic control compared with randomly selected reprocessed HS (P = 0.01) and were significantly better for tissue sticking (P = 0.01), tissue transection (P = 0.02), tissue dissection (P < 0.01), grasping (P < 0.01), and hemostatic control (P = 0.04) compared with reprocessed HS with obvious defects. CONCLUSIONS: In vitro and in vivo data demonstrated significantly greater performance for new HS compared with reprocessed HS. Mechanical testing of reprocessed HS could not adequately distinguish which HS would result in decreased performance. These findings raise important issues of clinical safety in the contemporary quest for cost-effectiveness.