PCA3 molecular urine assay for prostate cancer: association with pathologic features and impact of collection protocols.

INTRODUCTION: PCA3 is a non-coding mRNA molecule that is overexpressed in prostate cancer. The purpose of this study is to evaluate the utility of the PCA3 molecular urine test scores to predict adverse pathologic features and catheterized specimen collection. METHODS: Hundred men with clinically localized prostate cancer scheduled to undergo robotic prostatectomy were enrolled in the study following a standard consent process. The study protocol consisted of providing four urine samples. Voided urine obtained following digital rectal examination (DRE) pre-operatively (Vl), catheterized urine without DRE (V2), and l0-day and 6-week postoperative voided (V3 and V4) urine samples were collected and analyzed. These four urine specimens underwent target capture, transcription-mediated amplification, and hybridization in order to quantify both PCA3 and PSA mRNA. The PCA3 score was calculated as the ratio of PCA3 to PSA. RESULTS: Informative rates (sufficient mRNA for analysis) for VI, V2, V3 and V4 were 91, 85, 0 and 2%, respectively. There was no significant associations with pathological stage, Gleason score >6. Higher PCA3 scores at V1 correlated with increased risk for perineural invasion (P = 0.0479). CONCLUSIONS: Informative PCA3 scores can be obtained from post-DRE voided urine as well as catheterized urine without a DRE. The PCA3 test does not seem to predict adverse pathologic features, though, may have an association with perineural invasion. The ability of PCA3 score to predict clinical outcome remains to be determined.

Lymphadenectomy at the time of robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

OBJECTIVE: To evaluate the incidence of, and predictors for, lymphadenectomy in patients undergoing robot-assisted radical cystectomy (RARC) for bladder cancer. PATIENTS AND METHODS: Utilizing the International Robotic Cystectomy Consortium (IRCC) database, 527 patients were identified who underwent RARC at 15 institutions from 2003 to 2009. After stratification by age group, sex, pathological T stage, nodal status, sequential case number, institutional volume and surgeon volume, logistic regression was used to correlate variables to the likelihood of undergoing lymphadenectomy (defined as ≥ 10 nodes removed). RESULTS: Of the 527 patients, 437 (82.9%) underwent lymphadenectomy. A mean of 17.8 (range 0-68) lymph nodes were examined. Tumour stage, sequential case number, institution volume and surgeon volume were significantly associated with the likelihood of undergoing lymphadenectomy. Surgeon volume was most significantly associated with lymphadenectomy on multivariate analysis. High-volume surgeons (> 20 cases) were almost three times more likely to perform lymphadenectomy than lower-volume surgeons, all other variables being constant [odds ratio (OR) = 2.37; 95% confidence interval (CI) = 1.39-4.05; P = 0.002]. CONCLUSION: The rates of lymphadenectomy at RARC for advanced bladder cancer are similar to those of open cystectomy series using a large, multi-institutional cohort. There does, however, appear to be a learning curve associated with the performance of lymphadenectomy at RARC.

Robotic radical anterior pelvic exenteration: the UCI experience.

Robotic technology may be a promising tool in reduction of morbidity in radical anterior pelvic exenteration for invasive bladder cancer. We report our initial experience with robotic-assisted radical anterior pelvic exenteration in females in an attempt to evaluate the technique's feasibility and outcomes. A retrospective review of our bladder cancer database was performed. Twelve women that underwent robotic-assisted radical anterior pelvic exenteration, bilateral pelvic lymphadenectomy, and urinary diversion for clinically localized urothelial carcinoma of the bladder between 2004 and 2008 were included in this retrospective study. Median age was 73.0 +/- 9.6 years and median body mass index (BMI) was 23.5 +/- 5.0 kg/m2. Ten patients underwent ileal conduit diversion, one had an orthotopic neobladder and one an Indiana pouch. Median total operating time was 6.4 +/- 1.5 hours with median console and diversion times of 4.7 +/- 0.9 and 2.5 +/- 1.5 hours respectively. Median blood loss was 275.0 +/- 165.8 ml. Median length of stay was 8.0 +/- 1.6 days. Four patients were T2N0 or less, five T3N0, one T3N1 and two patients T4N0. There was one patient with positive surgical margins. Median number of lymph nodes removed was 23.0 +/- 11.4. Median follow-up of 9.0 +/- 6.0 months was available for ten patients. One had a recurrent ureteroenteric stricture, one had colpocleisis for vault prolapse, and three had metastatic disease. Robotic-assisted laparoscopic anterior pelvic exenteration appears to be a favorable surgical option with acceptable operative, pathological, and short-term clinical outcomes. According to the UCI experience, robotic anterior exenteration appears to achieve the clinical and oncologic goals for the surgical treatment of bladder cancer.

Does previous robot-assisted radical prostatectomy experience affect outcomes at robot-assisted radical cystectomy? Results from the International Robotic Cystectomy Consortium.

OBJECTIVES: To evaluate the effect of previous robot-assisted radical prostatectomy (RARP) case volume on the outcomes of robot-assisted radical cystectomy. Little is known regarding the effect of previous robotic surgical experience on the implementation and execution of robot-assisted radical cystectomy. METHODS: Using the International Robotic Cystectomy Consortium database, 496 patients were identified who had undergone robot-assisted radical cystectomy by 21 surgeons at 14 institutions from 2003 to 2009. The surgeons were divided into 4 groups according to their previous RARP experience (≤ 50, 51-100, 101-150, and > 150 cases). The overall operative time, blood loss, lymph node yield, pathologic stage, and surgical margin status were compared among the 4 groups using chi-square analysis. RESULTS: The mean operative time was 386 minutes (range 178-827). The mean estimated blood loss was 408 mL (range 25-3500). The operative time and blood loss were both significantly associated with previous RARP experience (P < .001). The mean lymph node count was 17.8 nodes (range 0-68). Lymph node yield and increased pathologic stage were significantly associated with previous RARP experience (P < .001). Finally, 34 (7.0%) of the 482 patients had a positive surgical margin. Margin status was not significantly associated with previous RARP experience (P = .089). CONCLUSIONS: Previous RARP case volume might affect the operative time, blood loss, and lymph node yield at robot-assisted radical cystectomy. In addition, surgeons with increased RARP experience operated on patients with more advanced tumors. Previous RARP experience, however, did not appear to affect the surgical margin status.

Robot-assisted laparoscopic transperitoneal pelvic lymphadenectomy and metastasectomy for melanoma: initial report of two cases.

Robotic pelvic lymphadenectomy is a well established procedure in the urologic and gynecologic literature. To our knowledge robotic pelvic lymphadectomy for metastatic melanoma has yet to be described. Herein we present the first report of robot-assisted pelvic lymphadenectomy in malignant melanoma. After placement of six laparoscopic ports (12 mm camera, three 8-mm robotic ports, 12-mm and 5-mm assistant ports) the DaVinci S robot (Intuitive Surgical, CA, USA) was docked in standard fashion with the patient in low lithotomy. In both cases the patients had enlarged pelvic lymph nodes on computed tomography and complete excision of these masses was accomplished along with complete lymphadenectomy extending from Cooper's ligament to just below the hypogastric artery in case 1 and to level of the bifurcation of aorta in case 2. A PK Maryland Dissector and monopolar scissors were used for dissection. Both patients were discharged on postoperative day #1. Robotic pelvic lymphadenectomy can be safely used for management of patients with metastatic melanoma involving the pelvic lymph nodes. Compared with the standard open procedure, pelvic lymphadenectomy with robotic assistance is associated with excellent vision and minimum morbidity.

Investigation of the ovarian and prostate cancer peptidome for candidate early detection markers using a novel nanoparticle biomarker capture technology.

Current efforts to identify protein biomarkers of disease use mainly mass spectrometry (MS) to analyze tissue and blood specimens. The low-molecular-weight "peptidome" is an attractive information archive because of the facile nature by which the low-molecular-weight information freely crosses the endothelial cell barrier of the vasculature, which provides opportunity to measure disease microenvironment-associated protein analytes secreted or shed into the extracellular interstitium and from there into the circulation. However, identifying useful protein biomarkers (peptidomic or not) which could be useful to detect early detection/monitoring of disease, toxicity, doping, or drug abuse has been severely hampered because even the most sophisticated, high-resolution MS technologies have lower sensitivities than those of the immunoassays technologies now routinely used in clinical practice. Identification of novel low abundance biomarkers that are indicative of early-stage events that likely exist in the sub-nanogram per milliliter concentration range of known markers, such as prostate-specific antigen, cannot be readily detected by current MS technologies. We have developed a new nanoparticle technology that can, in one step, capture, concentrate, and separate the peptidome from high-abundance blood proteins. Herein, we describe an initial pilot study whereby the peptidome content of ovarian and prostate cancer patients is investigated with this method. Differentially abundant candidate peptidome biomarkers that appear to be specific for early-stage ovarian and prostate cancer have been identified and reveal the potential utility for this new methodology.

Surgical margin status after robot assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

PURPOSE: Positive surgical margins at radical cystectomy confer a poor prognosis. We evaluated the incidence and predictors of positive surgical margins in patients who underwent robot assisted radical cystectomy for bladder cancer. MATERIALS AND METHODS: Using the International Robotic Cystectomy Consortium database we identified 513 patients who underwent robot assisted radical cystectomy, as done by a total of 22 surgeons at 15 institutions from 2003 to 2009. After stratification by age group, gender, pathological T stage, nodal status, sequential case number and institutional volume logistic regression was used to correlate variables with the likelihood of a positive surgical margin. RESULTS: Of the 513 patients 35 (6.8%) had a positive surgical margin. Increasing 10-year age group, lymph node positivity and higher pathological T stage were significantly associated with an increased likelihood of a positive margin (p = 0.010, <0.001 and p <0.001, respectively). Gender, sequential case number and institutional volume were not significantly associated with margin positivity. The rate of margin positive disease at cystectomy was 1.5% for pT2 or less, 8.8% for pT3 and 39% for pT4 disease. CONCLUSIONS: Positive surgical margin rates at robot assisted radical cystectomy for advanced bladder cancer were similar to those in open cystectomy series in a large, multi-institutional, prospective cohort. Sequential case number, a surrogate for the learning curve and institutional volume were not significantly associated with positive margins at robot assisted radical cystectomy.

The learning curve of robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

BACKGROUND: Robot-assisted radical cystectomy (RARC) has evolved as a minimally invasive alternative to open radical cystectomy for patients with invasive bladder cancer. OBJECTIVE: We sought to define the learning curve for RARC by evaluating results from a multicenter, contemporary, consecutive series of patients who underwent this procedure. DESIGN, SETTING, AND PARTICIPANTS: Utilizing the International Robotic Cystectomy Consortium database, a prospectively maintained and institutional review board-approved database, we identified 496 patients who underwent RARC by 21 surgeons at 14 institutions from 2003 to 2009. MEASUREMENTS: Cut-off points for operative time, lymph node yield (LNY), estimated blood loss (EBL), and margin positivity were identified. Using specifically designed statistical mixed models, we were able to inversely predict the number of patients required for an institution to reach the predetermined cut-off points. RESULTS AND LIMITATIONS: Mean operative time was 386 min, mean EBL was 408 ml, and mean LNY was 18. Overall, 34 of 482 patients (7%) had a positive surgical margin (PSM). Using statistical models, it was estimated that 21 patients were required for operative time to reach 6.5h and 8, 20, and 30 patients were required to reach an LNY of 12, 16, and 20, respectively. For all patients, PSM rates of <5% were achieved after 30 patients. For patients with pathologic stage higher than T2, PSM rates of <15% were achieved after 24 patients. CONCLUSIONS: RARC is a challenging procedure but is a technique that is reproducible throughout multiple centers. This report helps to define the learning curve for RARC and demonstrates an acceptable level of proficiency by the 30th case for proxy measures of RARC quality.

Robot-assisted radical cystectomy: an expert panel review of the current status and future direction.

OBJECTIVE: At the 9th Annual Meeting of the Society of Urologic Oncology (SUO), an expert panel discussed the current status of robot-assisted radical cystectomy (RARC). MATERIALS AND METHODS: The presentations were derived from: (1) review of published literature, unpublished addendums, and SUO abstracts, (2) initial abstract data of pooled results of 528 patients from the International Robot-Assisted Cystectomy Consortium (IRCC), and (3) an internet-based survey of the SUO membership (n = 54) on training and practice patterns related to RARC. RESULTS: Using pathologic assessment of surgical margins as a surrogate for cancer control, the results are favorable with organ confined disease, with select expert series showing no positive margins and the IRCC group reporting 4%. In non-organ-confined disease, select expert series also show no positive margins, while for the IRCC group it was 15%. The median lymph node yield in all series is 12-19 with 5%-33% positive. The S-model robot is preferred for an extended node dissection to the aortic bifurcation. In experienced hands, estimated blood loss is <500 cc, and hospital discharge by postoperative d 4-5. Complications appear similar to open and decrease with experience. In one study comparing RARC to open, pain scales were similar but morphine use was consistently lower for RARC. The technique is most often applied to the bladder and lymph nodes only with a mini-laparotomy for the diversion; technical considerations for female patients were described. The membership surveys showed that 37% of respondents have attempted RARC, but < 20% received robot console training during fellowship. The greatest area of concern was the adequacy of the lymph node dissection in the higher regions--common iliac to peri-caval/aortic. CONCLUSIONS: Initial reports of RARC demonstrate feasibility of technique, early oncologic outcomes, and learning curve experiences. Surgeons learning RARC should select patients without clinical evidence of locally advanced disease, and consider a second look open node dissection. Experienced surgeons have demonstrated the possibility of reduced blood loss, opiate requirement, and hospital stay. Moving forward, an international consortium has been organized to address the unmet needs of prospective comparisons with long-term oncologic outcomes, standardized complication reporting, and quality of life.

An initial characterization of the serum phosphoproteome.

Phosphorylation is a dynamic post-translational protein modification that is the basis of a general mechanism for maintaining and regulating protein structure and function, and of course underpins key cellular processes through signal transduction. In the last several years, many studies of large-scale profiling of phosphoproteins and mapping phosphorylation sites from cultured human cells or tissues by mass spectrometry technique have been published; however, there is little information on general (or global) phosphoproteomic characterization and description of the content of phosphoprotein analytes within the circulation. Circulating phosphoproteins and phosphopeptides could represent important disease biomarkers because of their well-known importance in cellular function, and these analytes frequently are mutated and activated in human diseases such as cancer. Here, we report an initial attempt to characterize the phosphoprotein content of serum. To accomplish this, we developed a method in which phosphopeptides are enriched from digested serum proteins and analyzed by LC-MS/MS using LTQ-Orbitrap (CID) and LTQ-ETD mass spectrometers. With this approach, we identified approximately 100 unique phosphopeptides with stringent filtering criteria and a lower than 1% false discovery rate.

Periprostatic adipose tissue as a modulator of prostate cancer aggressiveness.

PURPOSE: Adipose tissue has been suggested to contribute to the pathogenesis of various disease states, including prostate cancer. We investigated the association of cytokines and growth factors secreted by periprostatic adipose tissue with pathological features of aggressive prostate cancer. MATERIALS AND METHODS: Periprostatic adipose tissue was harvested from patients undergoing radical prostatectomy and cultured for 24 hours to generate conditioned medium or snap frozen immediately for functional signaling profiling. Multiplex analysis of the periprostatic adipose tissue conditioned medium was used to detect cytokine levels and compared to patient matched serum from 7 patients. Interleukin-6 in serum and periprostatic adipose tissue conditioned medium was further analyzed by enzyme-linked immunosorbent assay and correlated with clinical variables, such as age, body mass index and Gleason score, in 45 patients. Interleukin-6 expression in periprostatic adipose tissue was determined by immunohistochemistry. Reverse phase protein microarray technology was used to analyze cell signaling networks in periprostatic adipose tissue. RESULTS: Interleukin-6 in periprostatic adipose tissue conditioned medium was approximately 375 times greater than that in patient matched serum and levels correlated with pathological grade. This finding was further extended by cell signaling analysis of periprostatic adipose tissue, which showed greater phosphorylation on Stat3 with high grade tumors (any component of Gleason score 4 or 5). CONCLUSIONS: Higher Gleason score correlated with high levels of conditioned medium derived interleukin-6. Moreover, cell signaling analysis of periprostatic adipose tissue identified activated signaling molecules, including STAT3, that correlated with Gleason score. Since STAT3 is interleukin-6 regulated, these findings suggest that periprostatic adipose tissue may have a role in modulating prostate cancer aggressiveness by serving as a source of interleukin-6. Also, we found low numbers of inflammatory cells in the fat, suggesting that adipocytes are the major secretors of interleukin-6.

The increased expression of periostin during early stages of prostate cancer and advanced stages of cancer stroma.

BACKGROUND: Three-dimensional culture (3DC) is a relevant in vitro model used to study prostate development and carcinogenesis. Recent studies have indicated that 3DC-associated genes would be more sensitive as prognostic markers for cancer; however, no 3DC-associated genes in prostate cancer (CaP) have thus far been elucidated. METHODS: Candidate 3DC-associated genes in non-malignant prostatic epithelial cells, RWPE-1 and TA2, were selected, based on a comparison of microarray gene expression data between cells grown in two-dimensional culture (2DC) and in 3DC. To extract CaP-associated genes among the 3DC-associated genes, gene expression levels from the microdissected tissue samples were compared between 20 well-differentiated or 20 poorly differentiated CaP, as well as matched normal prostate epithelium. The expression levels of CaP-associated genes in 3DC were validated by quantitative RT-PCR using TA2 cells in 2DC and 3DC. Protein expression of periostin (POSTN), which is one of the 3DC CaP-associated genes, was further evaluated in the clinical samples by immunohistochemistry. RESULTS: Several genes including POSTN were identified as CaP-associated genes using a 3DC system. Immunohistochemical analyses revealed that POSTN expression was increased in the early stages of CaP (Gleason score 6-7), but not in the advanced stages of CaP. Furthermore, the positive ratio observed for the expression of POSTN in tumor-associated stroma was significantly correlated with the degree of malignancy. CONCLUSIONS: POSTN, one of the 3DC-associated genes, may serve as a potential biomarker for predicting the pathological grade and prognosis of CaP. Prostate 69: 1398-1403, 2009. (c) 2009 Wiley-Liss, Inc.

Loss of annexin A1 disrupts normal prostate glandular structure by inducing autocrine IL-6 signaling.

Annexin A1 (ANXA1) expression is commonly reduced in premalignant lesions and prostate cancer, but a causal relationship of ANAX1 loss with carcinogenesis has not been established. ANXA1 levels have been shown to inversely correlate with interleukin 6 (IL-6) expression in other cell types and IL-6 has been suggested to enhance prostate cancer initiation and promotion. To investigate whether loss of ANXA1 may contribute to prostate carcinogenesis, ANXA1 expression was reduced using RNA interference in non-tumorigenic human prostatic epithelial cells (RWPE-1/rA1). No effect on morphology, apoptosis, migration or anchorage-dependent or -independent growth was detected. However, IL-6 mRNA and secreted protein levels were elevated in RWPE-1/rA1 cells. In addition, re-expression of ANXA1 in these cells suppressed IL-6 secretion, and altering ANXA1 levels in prostate cancer cells had similar effects on IL-6. The effects of ANXA1 loss and increased IL-6 expression on prostate epithelium were examined using an assay of acinar morphogenesis in vitro. Acini formed by RWPE-1/rA1 cells had delayed luminal clearing and larger mean diameters than control cells. The RWPE-1/rA1 phenotype was recapitulated by treating control cells with recombinant IL-6 and was reversed in RWPE-1/rA1 cells by blocking IL-6 bioactivity. Taken together, these data support a direct role for decreased ANXA1 expression in prostate carcinogenesis and enhancing tumor aggressiveness via the upregulation of IL-6 expression and activity.

Posterior reconstruction and anterior suspension with single anastomotic suture in robot-assisted laparoscopic radical prostatectomy: a simple method to improve early return of continence.

Post-prostatectomy urinary incontinence is a major cause of morbidity from radical prostatectomy. Efforts have been made to develop techniques to hasten return of urinary control. Several authors have demonstrated improved early continence with anterior, posterior, or combined reconstruction of the urethral-pelvic attachments. In this study, we compare three-month urinary function and continence data for patients who underwent RALP with posterior reconstruction and anterior suspension with single anastomotic suture (PRASS). A prospective cohort of 50 patients underwent RALP with PRASS reconstruction and were compared to 50 control patients who underwent standard RALP. Continence was defined as use of 0-1 urinary pads and was evaluated at each follow-up visit using the EPIC-26 questionnaire. A weighted summary score was created and group differences were compared using a repeated measures analysis of variance model. After adjusting for age, baseline AUA symptom score, and SHIM scores, which were found to correlate with continence, patients who underwent the PRASS reconstruction had significantly improved urinary control at three months compared with the control group; 90.9% of the patients in the PRASS group wore 0-1 pads per day versus 48.2% in the control group (P = 0.014). Of the patients undergoing the standard prostatectomy 20.6% were totally pad-free compared with 42% of the patients undergoing the PRASS procedure (P = 0.042). In conclusion, the PRASS technique resulted in statistically significant improvement in urinary control three months post-operation. The PRASS reconstruction is technically straightforward, requires no additional sutures, and is a simple technique that is easily learned and adaptable to other robotic surgery.

Pelvic lymph node dissection and outcome of robot-assisted radical cystectomy for bladder carcinoma.

INTRODUCTION: Pelvic lymph node dissection (PLND) at the time of radical cystectomy for urothelial carcinoma of the bladder is critical for accurate staging and may improve oncologic outcomes. Minimally invasive approaches have been criticized for limiting the extent of the PLND. We reviewed our experience with PLND and its perioperative outcomes with robot-assisted laparoscopic radical cystectomy (RARC). METHODS: Data were collected prospectively from 50 patients scheduled for RARC. Included in the analysis were patients who had RARC and a standard PLND. The entire extirpative portion of the procedure was performed using the da Vinci Robot (Intuitive Surgical, Sunnyvale, CA, USA). RESULTS: A total of 41 patients were included in the study: 30 men and 11 women with a mean age of 69.7 years (range 49-85) and a mean body mass index of 26.9 (range 19.5-43.7). The median total operative time was 497.77 min (320-805). The mean estimated blood loss was 253.66 ml (range 50-700). The transfusion rate was 44% (18 out of 41) ranging from 0 to 4 units (median 0 units of blood). The mean total number of lymph nodes retrieved was 25.07 (range 4-68). Nodal metastases were seen in 14.63% (6/41). Rate of positive surgical margin was 4.87% (2/41). The median length of hospital stay was 8 days (5-37). The median duration of nasogastric tube, time to ambulation, first clear liquid intake, passage of colonic gas, time to bowel movement, and start of solid food intake were 1 (0-5), 2 (1-7), 3 (2-10), 4 (1-6), 5 (2-11) and 6 days (3-24), respectively. CONCLUSION: An adequate PLND, comparable with that recommended for open surgery, can be performed safely with robot assistance. The perioperative outcomes were likewise comparable with that of the gold standard, open cystectomy.

Annexin A2 positively contributes to the malignant phenotype and secretion of IL-6 in DU145 prostate cancer cells.

Several groups, including ours, have reported that annexin A2 (ANXA2) expression is reduced in most prostate cancer (CaP). More recently, however, we reported that ANXA2 is expressed in some high-grade tumors, but the biologic consequence of this is currently unknown. To elucidate the function of ANXA2 in CaP, we reduced its expression in DU145 cells using shRNA and tested the impact on characteristics of malignancy. Reduction of ANXA2 suppressed anchorage-dependent and -independent cell growth without affecting invasiveness. Interestingly, interleukin-6 (IL-6) secretion was reduced concomitantly with the reduction of ANXA2 but independently of S100A10. IL-6 expression was restored when wild type but not mutant ANXA2 was reexpressed in these cells. In a retrospective study of radical prostatectomy specimens from patients with nonmetastatic CaP, 100% of patients with ANXA2-positive tumors (n = 4) had a biochemical relapse while only 50% of patients with ANXA2 negative tumors (n = 20) relapsed, suggesting that ANXA2 expression in prostate tumors may be predictive of biochemical relapse. Significant cytoplasmic staining of ANXA2 was detected in 3 of 4 ANXA2-positive tumors, whereas ANXA2 is localized to the plasma membrane in benign prostatic glands. These finding, taken together, suggests a possible mechanism whereby ANXA2 expression positively contributes to an aggressive phenotype in a subset of CaP and suggest that ANXA2 has markedly different functions depending on its cellular context. Finally, this is the first description of a role for ANXA2 in IL-6 expression, and ANXA2 represents a new therapeutic target for reducing IL-6 in high-grade prostate cancer.

Long-term impact of a robot assisted laparoscopic prostatectomy mini fellowship training program on postgraduate urological practice patterns.

PURPOSE: Robot assisted laparoscopic prostatectomy has stimulated a great deal of interest among urologists. We evaluated whether a mini fellowship for robot assisted laparoscopic prostatectomy would enable postgraduate urologists to incorporate this new procedure into clinical practice. MATERIALS AND METHODS: From July 2003 to July 2006, 47 urologists participated in the robot assisted laparoscopic prostatectomy mini fellowship program. The 5-day course had a 1:2 faculty-to-attendee ratio. The curriculum included lectures, tutorials, surgical case observation, and inanimate, animate and cadaveric robotic skill training. Questionnaires assessing practice patterns 1, 2 and 3 years after the mini fellowship program were analyzed. RESULTS: One, 2 and 3 years after the program the response rate to the questionnaires was 89% (42 of 47 participants), 91% (32 of 35) and 88% (21 of 24), respectively. The percent of participants performing robot assisted laparoscopic prostatectomy in years 1 to 3 after the mini fellowship was 78% (33 of 42), 78% (25 of 32) and 86% (18 of 21), respectively. Among the surgeons performing the procedure there was a progressive increase in the number of cases each year with increasing time since the mini fellowship training. In the 3 attendees not performing the procedure 3 years after the mini fellowship training the reasons were lack of a robot, other partners performing it and a feeling of insufficient training to incorporate the procedure into clinical practice in 1 each. One, 2 and 3 years following the mini fellowship training program 83%, 84% and 90% of partnered attendees were performing robot assisted laparoscopic prostatectomy, while only 67%, 56% and 78% of solo attendees, respectively, were performing it at the same followup years. CONCLUSIONS: An intensive, dedicated 5-day educational course focused on learning robot assisted laparoscopic prostatectomy enabled most participants to successfully incorporate and maintain this procedure in clinical practice in the short term and long term.

Histological evaluation of cold versus hot cutting: clinical impact on margin status for laparoscopic partial nephrectomy.

PURPOSE: While most laparoscopic nephron sparing surgery is performed using cold scissors, energy based devices may also be used. A criticism of this approach has been the potential thermal destruction of the cellular architecture at the tumor margin, precluding the ability to accurately determine whether tumor cells are present. We clinically characterized the histological appearance of tumor margins excised with cold scissors, and bipolar and ultrasonic shears. MATERIALS AND METHODS: We evaluated 40 renal mass excisions performed by a total of 3 urologists at our institution between February 2003 and March 2007. There were 10 bipolar (5 mm LigaSure), 20 ultrasonic (Harmonic Scalpel) and 10 cold excisions. All slides were randomly evaluated twice by a single pathologist blinded to surgeon and excision method. Histological interpretation of the margin was scored as clear vs indeterminate. Variables, including margin fragmentation, artifact, extravascular blood clot, parenchymal hemorrhage, capillary congestion and vessel sealing, were assessed and scored on a scale of 0 to 3, that is 0--none, 1-1% to 25%, 2-26% to 50% and 3--greater than 50%. RESULTS: The pathologist was able to confidently identify cells at the margin as being malignant or benign in all cases. Histologically the ultrasonic scalpel demonstrated increased fragmentation and extravascular blood clotting compared with those of the other cutting methods (p <0.025 and <0.026, respectively). The ultrasonic scalpel also showed increased artifact depth compared to that of cold cutting (p <0.001). There were no statistical differences between the groups regarding margin artifact, parenchymal hemorrhage or capillary congestion. No statistical significance was observed in any variables between bipolar and cold cutting. CONCLUSIONS: Despite some degree of cellular damage the ability to determine whether cells at the margin were benign or malignant was not affected by using an energy based bipolar or ultrasonic device.

Proteomics of cancer of hormone-dependent tissues.

Serum and tissue biomarkers have begun to play an increasingly important role in the detection and management of many cancers of hormone-sensitive tissues. Specifically, the introduction of serum PSA measurements into clinical practice has dramatically altered detection and treatment of prostate cancer and serum tumor markers play a critical role in the management of testicular cancer. Serum biomarkers are used for ovarian and pancreatic cancers, but their usefulness is limited by poor specificity. Tissue biomarkers are used to help guide breast cancer treatment but are not widely used in other cancers. Even the "best" biomarkers such as PSA have substantial limitations. The discovery of new biomarkers for both early detection and prognosis of cancer is critical to the hope of better clinical outcomes. Recently there has been an expanding understanding of the underlying molecular etiology of cancer and molecular targeted therapies for some particularly aggressive cancers such as renal cell carcinoma have been developed. Better understanding of the molecular etiology of cancer and identification of additional therapeutic targets remain important research goals. Currently, there are very few patient-tailored therapies and there is a great need to better understand the molecular alterations associated with cancer and to use this information to design need cancer therapies and prevention strategies. Advances in proteomic technologies have created tremendous opportunities for biomarker discovery and biological studies of cancer. The potential that proteomics will impact clinical practice is currently greater than ever, but there main several obstacles in making this a reality. A major hurdle to overcome continues to be the proper acquisition of patient tissues and body fluids for investigation and clinical diagnostics. Each cancer has specific issues in this regard and it is incumbent upon investigators and collaborating clinicians to understand the various nuances of tissue and biofluid procurement. This chapter not only reviews the clinical need and potential impact of proteomic studies of hormone-sensitive cancers, but details specific technologies and discusses the issues surrounding tissue/biofluid procurement.