An analysis of leukapheresis and central venous catheter use in the randomized, placebo controlled, phase 3 IMPACT trial of Sipuleucel-T for metastatic castrate resistant prostate cancer.

PURPOSE: Sipuleucel-T is an autologous cellular immunotherapy. We review the safety of the leukapheresis procedure required for sipuleucel-T preparation and complications related to venous catheter use in the randomized, placebo controlled phase 3 IMPACT (IMmunotherapy for ProstAte Cancer Trial) study (NCT 00065442). MATERIALS AND METHODS: A total of 512 patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer were enrolled in the study. All patients were scheduled to undergo 3 standard 1.5 to 2.0 blood volume leukapheresis procedures at 2-week intervals. Leukapheresis related adverse events and those related to venous catheter use were reviewed. Immune cell counts were examined throughout the treatment course. RESULTS: Of 512 enrolled patients 506 underwent 1 or more leukapheresis procedures and were included in this analysis. Adverse events were comparable between the sipuleucel-T and control arms. Leukapheresis related adverse events were primarily associated with transient hypocalcemia (39.3%). Most leukapheresis related adverse events (97%) were of mild/moderate intensity. Median white blood cell count and absolute monocyte and lymphocyte counts were stable and within normal ranges throughout the treatment course. Of all patients 23.3% had a central venous catheter placed primarily for leukapheresis. Patients with vs without a central venous catheter had a higher risk of infection potentially related to catheter use (11.9% vs 1.3%, p <0.0001) and a trend toward a higher incidence of venous vascular events potentially related to catheter use, excluding the central nervous system (5.9% vs 2.1%, p = 0.06). CONCLUSIONS: Adverse events related to leukapheresis are manageable and quickly reversible. The majority of patients can undergo leukapheresis without a central venous catheter. Central venous catheters are associated with an increased risk of infections and venous vascular events. Peripheral intravenous access should be used when feasible.

Illinois statewide dual kidney transplantation experience--are we appropriately selecting kidneys?

PURPOSE: Dual kidney transplantation is a technique that some transplant centers have adopted to increase organ use. We investigated whether kidneys that were recovered and discarded were similar to those kidneys used for dual kidney transplantation. MATERIALS AND METHODS: We reviewed all kidneys recovered, biopsied and placed on machine perfusion in the state of Illinois from January 2002 to October 2009. We selected those kidneys used in dual kidney transplant, and compared their characteristics to those of kidneys that were recovered and biopsied but ultimately discarded. The immediate and 1-year outcomes of the dual kidney transplant recipients were analyzed. RESULTS: During the study period 60 dual transplants were performed while 94 kidney pairs were discarded. Overall donors from the used group had a lower mean creatinine clearance, older mean patient age, lower percentage of glomerulosclerosis, higher final flow rate and lower resistance. However, the comparison between those kidneys used successfully with 1-year graft survival and those discarded demonstrated only 3 less favorable parameters among the discarded group, namely a higher percentage of glomerulosclerosis (18.5% vs 13.9%, p=0.024), a higher degree of interstitial fibrosis and a higher final resistance (0.39 vs 0.31, p<0.001). CONCLUSIONS: The considerable overlap in demographics, histology and perfusion parameters between used and discarded kidneys suggests that many kidneys that were recovered and discarded could have been used in dual kidney transplantation with acceptable outcomes. This highlights the need for further study of how kidneys are selected and used.

Paclitaxel inhibits ureteral smooth muscle cell proliferation and collagen production in the absence of cell toxicity.

PURPOSE: Urinary tract stricture results from excess collagen deposition at an injured area. Paclitaxel (Sigma-Aldrich®) prevents coronary artery restenosis by inhibiting vascular smooth muscle cell proliferation and collagen production. We evaluated the effects of paclitaxel on ureteral smooth muscle cell proliferation and collagen production. MATERIALS AND METHODS: Three phases of experiments were done in canine smooth muscle cells. In phase 1 we used proliferation assay to study smooth muscle cells exposed to various concentrations of paclitaxel during 7 days. Phase 2 consisted of 6-day enzyme-linked immunosorbent assay to detect the total amount of type III collagen produced by smooth muscle cells exposed to paclitaxel. In phase 3 we assessed smooth muscle cell membrane damage using a lactate dehydrogenase cytotoxicity assay in which cells were exposed to escalating paclitaxel concentrations for 14 days. RESULTS: Proliferation studies showed that 10 and 100 nM paclitaxel significantly inhibited ureteral smooth muscle cell proliferation. Enzyme-linked immunosorbent assay revealed significantly decreased type III collagen production at 100 nM. Cytotoxicity testing showed that 1 to 100 nM paclitaxel did not harm smooth muscle cells. CONCLUSIONS: Paclitaxel effectively inhibits canine ureteral smooth muscle cell proliferation and collagen production without toxicity to smooth muscle cells at concentrations up to 100 nM. These results may ultimately translate into new methods of preventing and treating urinary stricture disease.

Size does matter: donor renal volume predicts recipient function following live donor renal transplantation.

PURPOSE: With the now routine use of computerized tomography angiography with 3-dimensional reconstruction in the donor evaluation, renal volume can be easily determined using volume calculating software. We evaluated whether donor renal volume could predict recipient renal function. MATERIALS AND METHODS: Clinical data of all donor and recipient pairs undergoing live donor kidney transplantation at our institution between January 2006 and October 2009 were reviewed. The volume of the kidney selected for transplant was determined using volume calculating software, and correlated to transplant recipient nadir and 1-year serum creatinine. Multivariate regression analysis was performed to adjust for demographic and clinical variables. RESULTS: During the study period 114 patients underwent live donor renal transplantation. Recipient nadir and 1-year serum creatinine levels were significantly correlated with the volume of donated kidney even after adjusting for age, body mass index, body surface area and donor creatinine clearance. Kidney volume also retained significance after excluding recipients from analysis who experienced acute rejection episodes. CONCLUSIONS: Larger kidney volumes calculated using 3-dimensional computerized tomography with volume calculating software are correlated with lower recipient nadir and 1-year serum creatinine levels.

Transplant tourism--a dangerous journey?

INTRODUCTION: While the ethical aspects of transplant tourism have received much attention recently, less has been written about the medical safety of this practice. We retrospectively evaluated the outcomes of patients who purchased organs internationally and presented to our center for follow-up care. METHODS: Baseline demographic characteristics were recorded. Post-operative outcomes including patient survival, graft survival, five-yr graft function, and complications were assessed. RESULTS: Eight patients who purchased international organs for transplant were identified. The country of transplant was China (n = 3), Pakistan (n = 3), India (n = 1), and the Philippines (n = 1). All patients were born in either Asia or the Middle East and traveled to the region of their ethnicity for transplantation. The mean time to presentation was 49 d post-operatively. The overall one- and two-yr patient survival rates were 87% and 75%, respectively. One patient died of miliary tuberculosis and another of Acinetobacter baumanii sepsis. There was one case of newly acquired hepatitis B infection. At last follow-up, all six surviving patients had functioning grafts with a mean creatinine level of 1.26 mg/dL at five yr. CONCLUSION: Although intermediate-term graft function is acceptable, the early morbidity and mortality among transplant tourists is high. These results suggest that the associated risks may not justify the trip.

Prognostic variables and nomograms for renal cell carcinoma.

The term renal cell carcinoma (RCC) is used to describe a heterogeneous group of tumors that vary histologically, genetically and molecularly. Extensive research has been conducted to identify characteristics that predict outcomes among patients with RCC. In addition to histological subtype these include tumor size, patient age, mode of presentation and various hematological indices, among others. Several groups have incorporated these clinical and pathological features into nomograms which help the clinician better define individual patient prognosis and direct the optimum therapeutic approach. In the present article we review these prognostic variables and nomograms for RCC.

Long-term outcomes of salvage radiotherapy for PSA-recurrent prostate cancer: validation of the Stephenson nomogram.

PURPOSE: Approximately one-third of patients who undergo radical prostatectomy for clinically localized prostate cancer will ultimately develop a biochemical recurrence. We report our long-term outcomes of salvage radiotherapy (SRT), and in so doing, validate a recently published prognostic nomogram. METHODS: A retrospective chart review was performed of all patients treated with SRT following radical prostatectomy for biochemical PSA recurrence at our institution between 1992 and 2003. We calculated the probability of 6-year biochemical progression-free survival following SRT and performed a goodness-of-fit test to ascertain whether the previously published nomogram correctly predicted our observations. RESULTS: During the study period, 96 patients were treated with SRT. At a median follow-up of 71 months, 44 (46%) had a durable PSA-free response. There was no significant difference between the observed progression-free survival and that predicted by the Stephenson nomogram (P = 0.7). Multivariate logistic regression analysis determined that PSA value at the initiation of SRT (P = 0.02) and pathologic Gleason Score (P = 0.04) were significantly associated with the probability of recurrence. CONCLUSIONS: During the study period, nearly half of patients treated with SRT for PSA recurrence following radical prostatectomy had a durable treatment response. We found the predictive nomogram developed by Stephenson, et al. to be valid when tested on our independent cohort of patients.

Risk factors for recurrence following radical cystectomy for pathologic node negative bladder cancer.

BACKGROUND AND OBJECTIVES: To evaluate for risk factors associated with bladder cancer recurrence in patients with pathologically negative lymph nodes. METHODS: A retrospective review of 405 patients undergoing radical cystectomy for bladder cancer between 1996 and 2008 was performed. Patients with node-positive disease and <6 months of follow up were excluded. Clinical and pathological characteristics including stage, lymphadenectomy type (standard vs. extended), number of nodes removed, margin status, lymphovascular invasion (LVI), perineural invasion (PNI), presence of carcinoma in situ, and site of recurrence were evaluated. Kaplan-Meier analysis was used to calculate 5-year recurrence-free survival stratified by lymph node yield. RESULTS: Two hundred sixty patients met the inclusion criteria. Overall, 80 (30.8%) patients recurred within 5 years. Univariate analysis identified LVI, PNI, extravesical disease, positive margins, and lymph node yield <14 to be significant predictors of disease recurrence. On multivariate analysis LVI, PNI, and node yield <14 retained significance (P = 0.01, 0.037, 0.038, respectively). There was no difference in 5-year recurrence free survival when stratified by node yield using the Kaplan-Meier method (P = 0.138). CONCLUSIONS: We identified LVI, PNI, and lymph node yield <14 as three independent risk factors for bladder cancer recurrence in patients with node-negative bladder cancer.

Endoscopic management of upper tract urothelial carcinoma.

While radical nephroureterectomy remains the gold standard of treatment for patients with upper tract urothelial tumors, technological advances have made endoscopic management possible. The careful selection of patients for such an approach is dependent upon an accurate diagnosis and an understanding of the natural history of the disease. High grade tumors behave aggressively and warrant radical extirpation unless an absolute contraindication exists. Motivated patients with low grade tumors and relative contraindications to nephroureterectomy can be managed with percutaneous or retrograde ureteroscopic techniques. High recurrence rates in the ipsilateral upper tract and bladder mandate close surveillance of patients treated conservatively. We review the important diagnostic, staging, technical, and surveillance issues in the endoscopic treatment of upper tract urothelial carcinoma.

The role of cytoreductive nephrectomy in the era of molecular targeted therapy.

While the widespread use of imaging has resulted in an increasing number of incidentally detected renal cancers, up to one third of patients present with metastatic disease and a significant number of those with clinically localized disease subsequently develop metastasis. The prognosis for patients with metastatic disease has traditionally been poor, with a 2-year survival of only 10 to 20%. However, over the past decade a number of developments have enhanced the treatment of these patients. Phase III trials have demonstrated a significant improvement in overall survival for well-selected patients undergoing cytoreductive nephrectomy prior to immunotherapy. Meanwhile, the recent introduction of molecular targeted agents has resulted in improved response rates and tolerability compared with immunotherapy, and has prompted a re-evaluation of the role and timing of surgery in patients with advanced disease. This review examines the role of surgical therapy for patients with metastatic disease in the new era of molecular targeted therapy.

Effect of the phosphodiesterase-5 inhibitor zaprinast on ischemia-reperfusion injury in rats.

PURPOSE: The cardiac and renal protective effects of phosphodiesterase-5 (PDE-5) inhibitors against ischemia-reperfusion injury have recently been demonstrated in animal studies. We evaluated the effect of pretreatment with the PDE-5 inhibitor zaprinast on warm renal ischemia in a rat model. METHODS: Female Sprague-Dawley rats underwent concomitant right nephrectomy and left renal hilar occlusion for 30 minutes. Twelve animals were equally divided into three groups: Group 1 received no pharmacologic pretreatment, group 2 was pretreated with zaprinast 10 mg/kg, and group 3 was pretreated with zaprinast 20 mg/kg. Zaprinast was dissolved in 25% dimethyl sulfoxide and given as a single intraperitoneal injection 30 minutes before surgery. Serum blood urea nitrogen (BUN) and creatinine levels, histopathology, and TUNEL staining for apoptosis were assessed 24 hours postoperatively. RESULTS: The mean creatinine level for groups 1, 2, and 3 was 0.73 mg/dL, 0.55 mg/dL, and 0.38 mg/dL, respectively. These values were not statistically different (P=0.099). The mean BUN levels of 35.8 mg/dL for group 1, 27.3 mg/dL for group 2, and 23.3 mg/dL for group 3 were also statistically similar (P=0.278). There were no objective differences in histopathologic evaluation or TUNEL staining between the groups. CONCLUSION: This study did not demonstrate a beneficial effect of zaprinast pretreatment on renal parameters after warm ischemic injury.

Multicenter experience with robot-assisted radical prostatectomy in renal transplant recipients.

OBJECTIVE: To evaluate our multi-institutional outcome with robot-assisted radical prostatectomy (RARP) in renal transplant recipients and describe technical modifications of the procedure. MATERIALS AND METHODS: We retrospectively reviewed 1677 patients, 1422 from Mayo Clinic Arizona and 255 from Loyola University Medical Center, undergoing RARP from March 2004 to October 2010, of which 7 were renal transplant recipients. Baseline demographic features, perioperative data, and oncologic outcomes were reviewed. RESULTS: At diagnosis, mean patient age was 63.3 years and serum prostate specific antigen was 6.17 ng/mL. The mean total operative time was 186 minutes (range, 80-210 minutes). No intraoperative complications were noted. The mean hospital length of stay was 1.8 days (range, 1-3 days). Clavien grade II postoperative complications occurred in 3 of the 7 patients (42.9%), consisting of urosepsis, atrial fibrillation, and gross hematuria, all resolving with appropriate medical management. No significant changes were observed in graft function. Two patients (28.6%) had positive surgical margins. During a mean follow-up of 16 months, 1 patient with pathologic T3a, Gleason 9 cancer experienced a biochemical recurrence, which was treated with salvage external-beam radiation and androgen-deprivation therapy. CONCLUSION: Our series suggests that RARP is a safe and feasible form of therapy for localized prostate cancer in a select group of renal transplant recipients.

Updates on the use of ureteral stents: focus on the Resonance(®) stent.

The Resonance(®) metallic ureteral stent is one of the latest additions to the urologist's armamentarium in managing ureteral obstruction. One advantage of this stent over traditional polymer-based stents is resistance to encrustation with stone material, which allows longer dwell times and less frequent exchange procedures. Although exchanging a metallic stent is slightly more complicated than exchanging a polymer stent, the fluoroscopic techniques required are familiar to most urologists. The Resonance stent is also more resistant to compression by external forces, potentially allowing greater applicability in patients with metastatic cancer. Furthermore, the use of this stent in patients with benign ureteral obstruction is shown to be associated with significant cost reduction. Clinical studies on the use of this stent are accumulating and the results are mixed, although Level 1 evidence is lacking. In this article we present a comprehensive review of the available literature on the Resonance metallic ureteral stent.

Right renal vein aneurysm discovered incidentally during laparoscopic nephrectomy.

Renal vein aneurysms are exceedingly rare. There are only 8 reported cases in the literature. We present the first case of a renal vein aneurysm discovered incidentally during a laparoscopic radical nephrectomy and discuss its intraoperative management.

Cost analysis and clinical applicability of the Resonance metallic ureteral stent.

The Resonance metallic stent is a new wire-based ureteral stent that was initially developed for patients with malignant ureteral obstruction. Potential advantages over traditional stents include resistance to encrustation and to external compression, allowing for increased dwell times and the maintenance of upper tract drainage when traditional polymer stents have failed. We present a comparative cost analysis of Resonance metallic and standard polymer stent use in patients with benign urinary obstruction and review the literature regarding the Resonance stent.

Metallic ureteral stents: a cost-effective method of managing benign upper tract obstruction.

INTRODUCTION: The management of patients with upper urinary tract obstruction who are not candidates for definitive reconstruction often presents a challenge. We report our initial experience with the Resonance (Cook Urological, Spencer, IN) metallic ureteral stent for the management of benign ureteral obstruction and present a comparative cost analysis of metallic to standard polymer stent use. METHODS: Data were retrospectively gathered on all patients undergoing metallic ureteral stent placement for benign causes from July 2007 to February 2009. Baseline demographics, previous method of drainage, pre- and postoperative creatinine levels, procedural complications, stent-related side effects, and metallic stent dwell time were recorded. The cost of stent maintenance for polymer and metallic stents for a 12-month interval was calculated for each patient. RESULTS: Fifteen stents were placed in 13 patients to manage obstruction due to a variety of benign etiologies. Metallic stents provided adequate drainage in 12/13 patients, but were discontinued prematurely in 3 patients (2 for voiding symptoms, 1 for hematuria). Eight patients had their metallic stents changed after a mean time of 11.6 months, with no encrustation. The yearly cost associated with polymer and metallic stent use was $23,999 and $11,183, respectively. This amounted to a $10,394 annual cost reduction (43%) for each patient. CONCLUSIONS: Metallic ureteral stents provide effective upper tract drainage for the majority of patients with benign upper tract obstruction, with significant cost benefit, largely because of the shorter exchange interval.

A novel technique for the removal of minimally encrusted ureteral stents.

The removal of encrusted ureteral stents typically necessitates secondary treatment modalities, such as ureteroscopy, extracorporeal shock wave lithotripsy, or antegrade nephroscopy. We present a novel technique for the removal of minimally encrusted stents using a suture and a ureteral access sheath.

Pseudodistal ureteral stone resulting from calcified Deflux implantation.

Vesicoureteral reflux (VUR) is a common clinical problem affecting 1% of pediatric patients. Subureteral endoscopic injection of dextranomer/hyaluronic acid (Deflux) is a minimally invasive treatment option for VUR that is rapidly gaining popularity. Histologic studies have demonstrated that in a minority of patients, the Deflux injection site can be associated with microcalcification. We report the case of a 12-year-old girl with a history of VUR who had previously been treated with Deflux and presented with abdominal pain and was noted to have a small hyperdense mass in the bladder wall on imaging. The presumptive diagnosis of a distal ureteral stone was ultimately ruled out by cystoscopy and retrograde pyelography, which revealed that the lesion seen on imaging represented the intramural Deflux deposit. This is the second reported case in which a calcified Deflux implant was mistaken for a distal ureteral stone in a patient presenting with abdominal pain.

Comparison of open and robot-assisted pelvic lymphadenectomy for prostate cancer.

PURPOSE: We evaluated whether there were differences in the lymph node yield and incidence of nodal metastasis among patients undergoing robot-assisted radical prostatectomy with pelvic lymphadenectomy (LAD) and open radical retropubic prostatectomy with either a standard or extended node dissection. PATIENTS AND METHODS: Data were collected retrospectively on all patients undergoing radical prostatectomy with pelvic LAD at our institution between January 2006 and December 2008. Patients in group 1 (n = 60) underwent robot-assisted standard LAD, those in group 2 (n = 64) had open standard LAD, and group 3 patients (n = 43) were treated with open extended LAD. Statistical comparison was then made between the three groups stratified by histologic grade and pathologic stage. RESULTS: The mean lymph node yield was 8.2 for group 1, 7.6 for group 2, and 14.8 for group 3. The overall incidence of positive nodes in each group was 3.3%, 1.6%, and 18.6%, respectively. There were no differences between the node counts (P = 0.84) and probability of finding positive nodes between the robot-assisted and open standard dissections. The extended LAD identified patients with positive nodes at a greater frequency, although those patients were more likely to have adverse pathologic features. Complications related to the lymphadenectomy were not different between the groups. CONCLUSION: The lymph node yield obtained during robot-assisted pelvic lymphadenectomy for prostate cancer is comparable to an open approach using a similar template. An open extended node dissection yields more nodes and identifies a greater number of patients with lymph node involvement.

Saline Mobilization of the Colon during Percutaneous Renal Cryoablation.

A 62-year-old woman with a history of multiple abdominal surgeries underwent computed tomography-guided percutaneous renal cryoablation for a 1.5-cm enhancing left renal mass. We describe the technique of salinoma formation to displace the colon away from the tumor to avoid colonic injury during cryoablation.