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Objective To culture prostate cells from fresh biopsy core samples from radical prostatectomy (RP) tissue. Further, given the genetic heterogeneity of prostate cells, the ability to culture single cells from primary prostate tissue may be of importance toward enabling single-cell characterization of primary prostate tissue via molecular and cellular phenotypic biomarkers. Methods A total of 260 consecutive tissue samples from RPs were collected between October 2014 and January 2016, transported at 4°C in serum-free media to an off-site central laboratory, dissociated, and cultured. A culture protocol, including a proprietary extracellular matrix formulation (ECMf), was developed that supports rapid and short-term single-cell culture of primary human prostate cells derived from fresh RP samples. Results A total of 251 samples, derived from RP samples, yielded primary human tumor and nontumor prostate cells. Cultured cells on ECMf exhibit (1) survival after transport from the operating room to the off-site centralized laboratory, (2) robust (>80%) adhesion and survival, and (3) expression of different cell-type-specific markers. Cells derived from samples of increasing Gleason score exhibited a greater number of focal adhesions and more focal adhesion activation as measured by phospho-focal adhesion kinase (Y397) immunofluorescence when patient-derived cells were cultured on ECMf. Increased Ki67 immunofluorescence levels were observed in cells derived from cancerous RP tissue when compared to noncancerous RP tissue. Conclusion By utilizing a unique and defined extracellular matrix protein formulation, tumor and nontumor cells derived from primary human prostate tissue can be rapidly cultured and analyzed within 72 hours after harvesting from RP tissue.

Background Laparoscopic cryoablation (LCA) and percutaneous cryoablation (PCA) of small renal masses have gained popularity, but only limited data exist on the complication rates. Objectives In this study, we report on postoperative complications associated with LCA and PCA in a single tertiary center experience. Design, setting, and participants We conducted a retrospective review of electronic medical records for patients undergoing LCA or PCA between 2001 and 2008 at our institution. Interventions All patients underwent LCA or PCA. Measurements Demographics, radiographic variables, and complication rates were compared between the two groups. Complications were classified according to the modified Clavien system. Results and limitations Of a total of 195 patients included in this study, 72 underwent LCA and 123 underwent PCA. There were no differences in demographics between the groups. We observed complications in 10 LCA procedures (13.9%) and 26 PCA procedures (21.1%) ( p =0.253). The distribution of the complications differed significantly between the groups with mild complications (grades 1 and 2) more common in the PCA group (20.3% vs 5.6%, respectively; p =0.001), whereas severe events (grades 3 and 4) were more frequent in the LCA group (8.3% vs 0.8%, respectively; p =0.011). On multivariate analysis, age and body mass index were inversely associated with complications, whereas female gender, multiple tumors, and preexisting comorbidities showed a trend toward increased risk. Conclusions LCA and PCA, although minimally invasive, are not void of complications. Most of the complications encountered are mild; however, severe (grade 3 or 4) events may occur in up to 3.6% of patients. PCA may be associated with a higher rate of complications, although most of these are mild and transient. However, on multivariate analysis, the chosen ablative approach (laparoscopic or percutaneous) is not associated with the risk of complications.

Multifocal renal cell carcinoma (RCC) has been reported in up to 25% of all radical nephrectomy specimens. Modern imaging tends to underestimate the rate of multifocality. Recognition of multifocality before treatment may guide physicians and patients to the type of intervention and tailor long-term follow-up.Our aim was to develop and assess preoperative nomograms to predict occult multifocal RCC.We evaluated 560 consecutive patients undergoing radical nephrectomy for clinically localized suspected sporadic RCC between 2000 and 2008 in a tertiary center. Clinically manifest multifocal lesions were excluded. Logistic regression models were used to assess the potential risk factors of occult multifocality with and without pathologic variables that may be available with preoperative biopsy. Nomograms were developed and assessed for diagnostic properties.All patients underwent radical nephrectomy.Assessments of risk factors for occult multifocal RCC were obtained using regression models and nomograms.The incidence of occult multifocality was 7.9%. Significantly associated predictors of multifocality were male gender, family history of malignancy other than RCC, radiographic size of the lesion, histologic subtype other than clear cell, and Fuhrman grade IV. The two designed nomograms had 0.75 and 0.82 concordance indices, respectively.Our data suggest that occult multifocal RCC is more frequently associated with small (2-4 cm) renal lesions. Male gender, family history of kidney cancer, histologic subtype, and grade are strongly associated with an increased risk of occult multifocal RCC. The developed nomograms had good predictive accuracy that was enhanced when combined with pathologic variables.

To compare the effects of tumor volume (TV), tumor percentage involvement (TPI), and prostate volume (PV) on prostate-specific antigen (PSA) recurrence (PSAR) after radical prostatectomy (RP).A cohort of 3528 patients receiving RP between 1988 and 2008 was retrieved from the Duke Prostate Center. Patients were stratified by TV (3, 3-6,6 cm(3)), TPI (10%, 10%-20%,20%), and PV (35, 35-45,45 cm(3)) and their effects on PSAR evaluated using Kaplan-Meier analysis. Clinicopathologic variables included in univariate analysis were age at surgery, race, year of surgery, PSA, pathologic Gleason score, pathologic tumor stage, margin status, extracapsular extension, and seminal vesicle invasion. The effects of TV, TPI, and PV (as continuous and categorical variables) on PSAR were compared using Cox analysis.TPI, TV, and PV were predictive of PSAR (P.05) in Kaplan-Meier analysis. In multivariate analysis as continuous variables, TPI and PV were predictive of PSAR (hazard ratio [HR] = 1.16 and HR = 0.65, P.05). As categorical variables, TPI20% and PV 10-35 cm(3) were predictive of PSAR (HR = 1.45 and OR = 1.25, P.05). TV was not predictive of PSAR in either analysis. Pathologic Gleason scoreor = 7, PSA, positive margins, seminal vesicle invasion, and tumor stage T3/T4 were found to be predictors of PSAR (P.05).TV, TPI, and PV were predictive of PSAR in univariate analysis, but in multivariate analysis, only TPI and PV were predictive of PSAR. TPI and PV should be considered when evaluating, assessing, and counseling patients regarding PSAR risk.

To clarify the relationship between age and pathologic Gleason score and their effect on prostate-specific antigen recurrence (PSAR).The data from a cohort of 2911 men who had undergone radical prostatectomy from 1988 to 2006 were retrieved from the Duke Prostate Center database. Patient age was divided into 3 groups:60, 60-64, andor=65 years. The pathologic Gleason score was divided into 5 groups:or=5, 6, 3 + 4, 4 + 3, and7. PSAR was defined as the prostate-specific antigen level increasing to0.2 ng/mL30 days after radical prostatectomy. The associations between age and pathologic Gleason score on PSAR and the time to PSAR were analyzed using parametric, nonparametric, Kaplan-Meier, and Cox regression techniques.Patient age and interval to PSAR had no significant association (P.05). Kaplan-Meier analysis demonstrated a significant difference in PSAR among age groups. The pathologic Gleason scores of 3 + 3, 3 + 4, 4 + 3, and7 were significant in determining the incidence of PSAR. Age was not significant for PSAR in patients with a pathologic Gleason score ofor=7. In patients with a pathologic Gleason score of7, a statistically significant difference was observed among the age groups. Men60 years old with a pathologic Gleason score7 had a lower incidence of PSAR than did older men with a similar pathologic Gleason score. A pathologic Gleason score ofor=6 was significant in predicting PSAR.Age alone was an independent factor in predicting PSAR, but not in predicting the interval to PSAR. The pathologic Gleason score remained a predictor of PSAR, and patient age should be considered in patients with a pathologic Gleason score7.

Purpose The Partin tables represent one of the most widely used prostate cancer staging tools for seminal vesicle invasion (SVI) prediction. Recently, Gallina et al. reported a novel staging tool for the prediction of SVI that further incorporated the use of the percentage of positive biopsy cores. We performed an external validation of the Gallina et al. nomogram and the 2007 Partin tables in a large, multi-institutional North American cohort of men treated with robotic-assisted radical prostatectomy. Methods and Materials Clinical and pathologic data were prospectively gathered from 2,606 patients treated with robotic-assisted radical prostatectomy at one of four North American robotic referral centers between 2002 and 2007. Discrimination was quantified with the area under the receiver operating characteristics curve. The calibration compared the predicted and observed SVI rates throughout the entire range of predictions. Results At robotic-assisted radical prostatectomy, SVI was recorded in 4.2% of patients. The discriminant properties of the Gallina et al. nomogram resulted in 81% accuracy compared with 78% for the 2007 Partin tables. The Gallina et al. nomogram overestimated the true rate of SVI. Conversely, the Partin tables underestimated the true rate of SVI. Conclusion The Gallina et al. nomogram offers greater accuracy (81%) than the 2007 Partin tables (78%). However, both tools are associated with calibration limitations that need to be acknowledged and considered before their implementation into clinical practice.

We evaluated the learning curves and perioperative outcomes of an experienced laparoscopic surgeon and his trainees to assess our structured teaching program.We retrieved 383 patients undergoing robot-assisted laparoscopic prostatectomy (RALP) from our database. Trainees completed a structured teaching program and were categorized as early (days 0 to 232), mid (days 566 to 797), and late (days 825 to 1218) according to the time period in which they were working with the mentor. We compared operative times, estimated blood loss (EBL), and positive surgical margin (PSM) rates between the trainees and the mentor (Mann-Whitney and Chi-square test). Association of EBL, body mass index (BMI), and prostate weight with operative time was evaluated in multivariate linear regression analysis.Median operative times of the early, mid, and late trainees (258, 220, and 200 minutes) significantly decreased and were similar to the corresponding senior surgeon's (254, 242, and 180 minutes). Operative times decreased with lower BMI, EBL, and prostate weight (P = 0.006, P0.001, and P0.001, respectively). Overall, EBL (150 mL vs. 150 mL, P = 0.215) and PSM rates (20% vs. 18.6%, P = 0.741) did not differ between the mentor and the trainees.A structured teaching program for RALP is effective and trainees are able to adopt the increased efficiency and skills of their mentor. Lower BMI, EBL, and prostate weight were associated with shorter operative times. Trainees performing the procedure did not negatively affect EBL and positive surgical margin rate.

Objectives To analyze the long-term incidence of ureteral stricture formation in a series of patients in whom a new-generation ureteral access sheath was used. A new generation of ureteral access sheaths has been developed to facilitate ureteroscopic procedures. However, some have questioned their safety and whether the device might cause significant ureteral trauma. Methods Between September 1999 and July 2001, 150 consecutive ureteroscopic procedures with adjunctive use of an access sheath were performed. A retrospective chart review to April 2002 was done. Of the 150 patients, 130 underwent ureteroscopy for ureteral stones. Patients who underwent endoureterotomy or treatment of transitional cell carcinoma were excluded from this analysis. Sixty-two patients had follow-up greater than 3 months and were included in the analysis. Overall, 71 ureteroscopic procedures were performed, with 9 patients undergoing multiple procedures. Ninety-two percent of the patients had pathologic findings above the iliac vessels. The average patient age was 45.3 years (range 17 to 76), and 70% and 30% of the patients were male and female, respectively. The mean clinical follow-up was 332 days (range 95 to 821), and follow-up imaging was performed within 3 months after ureteroscopy in all patients. Results The 10/12F access sheath was used in 8 ureteroscopic procedures (11.2%), the 12/14F access sheath in 56 (78.9%), and the 14/16F access sheath in 7 (9.8%). One stricture was identified on follow-up imaging of 71 procedures performed, for an incidence of 1.4%. The patient developed the stricture at the ureteropelvic junction after multiple ureteroscopic procedures to manage recurrent struvite calculi. The access sheath did not appear to be a contributing factor. Conclusions The results of our series indicate that the ureteral access sheath is safe and beneficial for routine use to facilitate flexible ureteroscopy. However, awareness of the potential ischemic effects with the use of unnecessarily large sheaths for long periods in patients at risk of ischemic injury should be considered. We advocate the routine use of the device for most flexible ureteroscopic procedures proximal to the iliac vessels.

Objectives To assess methods to improve the longevity and durability of flexible ureteroscopes by using the ureteral access sheath, 200-μm holmium laser fiber, and nitinol baskets or graspers during routine ureteroscopic procedures. Despite adequate advances in fiberoptics and endoscope design, the decreased size of currently available flexible ureteroscopes makes damage inevitable after repeated use. However, new auxiliary tools may be able to enhance ureteroscope durability. Methods The indications for performing flexible ureteroscopy were proximal ureteral stones (n = 32), renal calculi (n = 59), treatment of upper tract transitional cell carcinoma (n = 3), evaluation of hematuria or filling defect (n = 7), and treatment of ureteral strictures or ureteropelvic junction obstruction (n = 8). Using four new 7.5F flexible ureteroscopes, we prospectively evaluated the number of passes of each ureteroscope until more than 20 optical fibers were broken, more than a 25° loss of deflection in either direction had occurred, or the instrument sustained injury requiring repair by the manufacturer. Results One hundred nine flexible ureteroscopic procedures (average 27.5 procedures per instrument; range 19 to 34) were performed with the four new flexible ureteroscopes before being sent for repair. Adjuncts to reduce scope damage during these procedures were the use of the ureteral access sheath (n = 109), nitinol devices allowing lower pole stone retrieval (n = 27), and the 200-μm holmium laser fiber for stone fragmentation, tumor ablation, and incision of ureteropelvic junction/ureteral stenoses (n = 91). The average number of passes until more than 20 optical fibers were broken was 15.3 (range 12 to 20), until more than a 25° loss of deflection occurred was 50.3 (range 42 to 66), or until the scope required repair was 66.7 (range 46 to 82). Conclusions Flexible ureteroscopy will be used increasingly to manage upper urinary tract pathologic findings. Historically, the number of procedures performed before a flexible ureteroscope requires repair averaged 6 to 15. By incorporating the new ureteroscopic accessories, such as nitinol devices, a ureteral access sheath, and the 200-μm holmium laser fiber into common practice, one can reduce the strain on these fragile 7.5F endoscopes, thereby maximizing their longevity.

Great strides have been made in the discovery of alternative tissue approximation techniques for use in laparoscopy. Although none of the techniques have eliminated the need for suturing laparoscopically, their potential in achieving this end is promising. When an ideal approximation technique is discovered that is easy to use, safe, and reliably able to hold tissue together laparoscopically, laparoscopic reconstructive surgery should become less formidable and more appealing to urologists.

Objectives. Laparoscopy may be complicated by neuromuscular injuries, both to the patient and to the surgeon. We used a survey to estimate the incidence of these injuries during urologic laparoscopic surgery, to assess risk factors for these injuries, and to determine preventive measures. Methods. A survey of neuromuscular injuries associated with laparoscopy submitted to 18 institutions in the United States was completed by 18 attending urologists from 15 institutions. Results. From among a total of 1651 procedures, there were 46 neuromuscular injuries in 45 patients (2.7%), including abdominal wall neuralgia (14), extremity sensory deficit (12), extremity motor deficit (8), clinical rhabdomyolysis (6), shoulder contusion (4), and back spasm (2). Neuromuscular injuries were twice as common with upper retroperitoneal as with pelvic laparoscopy (3.1% versus 1.5%). Among patients with neuromuscular injuries, those with rhabdomyolysis were heavier (means 91 versus 80 kg) and underwent longer procedures (means 379 versus 300 minutes), and those with motor deficits were older (means 51 versus 42 years of age). Of the surgeons, 28% and 17% reported frequent neck and shoulder pain, respectively. Conclusions. Although not common, neuromuscular injuries during laparoscopy do contribute to morbidity. Abdominal wall neuralgias, injuries to peripheral nerves, and joint or back injuries likely occur no more frequently than during open surgery, but risk of rhabdomyolysis may be increased. Positioning in a partial rather than full flank position may reduce the incidence of some injuries. Measures to reduce neuromuscular strain on the surgeon during laparoscopy should be considered.

Background: Postoperative peritoneal adhesion formation causes a multitude of disorders, including bowel obstruction and infertility. Methods: To test whether fibrin sealant inhibits adhesion formation, mice were given an intraperitoneal injection of talc (to induce adhesions) after which sealant was administered. Seven and 14 days later, the thickness of connective tissue between the fragmented mesothelium and the abdominal muscle was measured. Results: At both 7 and 14 days after talc administration, talc-treated mice had a 6-fold increase in connective tissue thickness over vehicle alone (P

We describe a simple and effective method using the Stone Cone to prevent migration of stone fragments into the ureter during percutaneous nephrolithotomy. This maneuver may reduce the need for antegrade ureteroscopy to remove residual fragments, thereby saving time and obviating the need for placement of an occlusion balloon.

Objectives . Significant obesity is considered to be a relative contraindication to laparoscopic surgery. This study reviews the complications encountered in massively obese patients undergoing urologic laparoscopic surgery. Methods . Body mass index (BMI) was used as an objective index to indicate massive obesity. Eleven institutions compiled retrospective data on 125 patients having a BMI greater than 30. Procedures performed included 76 pelvic lymph node dissections, 14 nephrectomies, 7 bladder neck suspensions, and 28 miscellaneous procedures. Results . For the group as a whole, the mean BMI was 35.1 (range 30.1 to 57.2). Mean operative time was 202 minutes (range 60 to 480). Conversion to open surgery occurred in 15 of the 125 patients (12%). Complication rates (minor and major) were 22% (27 occurrences in 125 patients) intraoperatively and 26% (33 occurrences in 125 patients) postoperatively. The major complications included 2 trocar injuries to abdominal wall vessels, 1 bladder injury, 3 peripheral nerve injuries, 1 dysrhythmia, 1 deep vein thrombosis, 1 wound seroma, 1 nephrocutaneous fistula, 1 incisional hernia, and 1 death. Conclusions . In this review, complication rates for urologic laparoscopic surgery on massively obese patientswere higher than in the general population undergoing laparoscopic surgery (0.3% to 21%).

Pelvic lymphadenectomy unquestionably is still the most accurate method to identify the presence or absence of lymphatic extension of prostate cancer. Lymphatic spread follows the lymph channels that leave the prostate posteriorly and then spread primarily to a lymphatic field of drainage that includes the perivesical, hypogastric, obturator, presacral, and presciatic lymph nodes. The obturator nodes are commonly the first site of meta~tasis.~' The risk of nodal involvement is increased with larger tumor volume and local periprostatic spreadlo; however, when only the histopathologic grade of the tumor is used, no method is precise in detecting positive pelvic lymph nodes with increasing Gleason score.2,18,22,28 At present, no imaging modality can identify accurately lymphatic involvement with prostate cancer. The role of CT scan in evaluating lymph node involvement is limited, with an accuracy rate of only 65%.3 In addition, microscopic nodal metastases cannot be demonstrated by CT scan in patients with advanced disease of the prostate (stages B,, C, or D).15,32 Unless the nodes are grossly enlarged, CT scan imaging of the prostate is limited as a staging tool for prostate cancer. The value of ultrasonography and magnetic resonance imaging for pelvic lymph node involvement is similar to that of CT scan, with a reported accuracy of 84% to 89%:~~~ Pedal lymphangiography, Color reproduction in this article courtesy of a grant by Tap Pharmaceuticals, Inc.

Background Multifocal renal cell carcinoma (RCC) has been reported in up to 25% of all radical nephrectomy specimens. Modern imaging tends to underestimate the rate of multifocality. Recognition of multifocality before treatment may guide physicians and patients to the type of intervention and tailor long-term follow-up. Objective Our aim was to develop and assess preoperative nomograms to predict occult multifocal RCC. Design, setting, and participants We evaluated 560 consecutive patients undergoing radical nephrectomy for clinically localized suspected sporadic RCC between 2000 and 2008 in a tertiary center. Clinically manifest multifocal lesions were excluded. Logistic regression models were used to assess the potential risk factors of occult multifocality with and without pathologic variables that may be available with preoperative biopsy. Nomograms were developed and assessed for diagnostic properties. Interventions All patients underwent radical nephrectomy. Measurements Assessments of risk factors for occult multifocal RCC were obtained using regression models and nomograms. Results and limitations The incidence of occult multifocality was 7.9%. Significantly associated predictors of multifocality were male gender, family history of malignancy other than RCC, radiographic size of the lesion, histologic subtype other than clear cell, and Fuhrman grade IV. The two designed nomograms had 0.75 and 0.82 concordance indices, respectively. Conclusions Our data suggest that occult multifocal RCC is more frequently associated with small (2–4cm) renal lesions. Male gender, family history of kidney cancer, histologic subtype, and grade are strongly associated with an increased risk of occult multifocal RCC. The developed nomograms had good predictive accuracy that was enhanced when combined with pathologic variables.