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.

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.

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.

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.

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.

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.

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.

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.

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.

Repair of rectal injury during robotic-assisted laparoscopic prostatectomy.

INTRODUCTION: Rectal injury is a potential devastating complication in radical prostatectomy. We reviewed the incidence and management of rectal injuries with robotic-assisted laparoscopic radical prostatectomy performed by a single surgeon. Of the first 251 robotic-assisted laparoscopic radical prostatectomies performed, 2 (0.8%) were complicated by rectal injury. TECHNICAL CONSIDERATIONS: All patients underwent bowel preparation and received preoperative intravenous antibiotics. Both rectal injuries were detected intraoperatively and treated robotically. The rectotomy was closed in two layers of absorbable sutures and imbricated with a nonabsorbable suture. The rectum was then tacked to the levator fibers on one side with nonabsorbable suture to pull the injury away from the vesicourethral anastomosis. An omental flap was developed and tacked posterior to the urethra to cover the repair. A closed suction drain was placed. After surgery, the patients received broad-spectrum intravenous antibiotics and resumed oral intake on postoperative day 1. At 2 weeks, the Foley catheter was removed after voiding cystourethrography confirmed no extravasation. CONCLUSIONS: Rectal injury during robotic-assisted laparoscopic radical prostatectomy can be identified and managed intraoperatively without requiring open conversion. A three-layer closure tacked away from the vesicourethral anastomosis and reinforced by an omental flap resulted in an uneventful recovery.

Robotic versus standard laparoscopic partial/wedge nephrectomy: a comparison of intraoperative and perioperative results from a single institution.

PURPOSE: Laparoscopic partial/wedge nephrectomy, similar to laparoscopic radical prostatectomy, is a technically challenging procedure that is performed by a limited number of expert laparoscopic surgeons. The incorporation of a robotic surgical interface has dramatically increased the use of minimally invasive pelvic surgery such that robotic laparoscopic radical prostatectomy is commonly performed even by laparoscopically naïve surgeons. This analysis compares the outcomes of our initial experience with robot-assisted laparoscopic partial nephrectomy (RLPN) performed by an experienced open surgeon to that of standard laparoscopic partial nephrectomy (LPN) performed by two experienced laparoscopic surgeons. PATIENTS AND METHODS: We reviewed the medical records of 11 consecutive patients who underwent 12 standard LPNs (EMM, RVC) (one patient had two unilateral tumors) and 10 consecutive patients (representing the first 11 of such robotic procedures performed at our institution) who underwent 11 RLPNs (one patient had bilateral tumors managed in an asynchronous manner) (DKO). RESULTS: The mean tumor size was 2.3 cm (range 1.7-6.2 cm) for LPN and 3.1 cm (range 2.5-4 cm) for RLPN. The mean total procedure time was 289.5 minutes (range 145-369 min) for LPN and 228.7 minutes (range 98-375 min) for RLPN (P=0.102). The mean estimated blood loss was 198 mL (range 75-500 mL) for LPN v 115 mL (25-300 mL) for RLPN (P=0.169). The mean warm ischemia time was 35.3 minutes (range 15-49 min) in the LPN group and 32.1 minutes (range 30-45 minutes) in the RLPN group (P=0.501). CONCLUSIONS: Introducing a robotic interface for laparoscopic partial/wedge resection allowed a fellowship-trained urologic oncologist with limited reconstructive laparoscopic experience to achieve results comparable to those for laparoscopic partial/wedge resection performed by experienced laparoscopic surgeons. In this regard, the learning curve appears truncated, similar to that with robot-assisted laparoscopic prostatectomy.

Robotic-assisted repair of iatrogenic ureteral ligation following robotic-assisted hysterectomy.

BACKGROUND AND OBJECTIVES: Ureteral injuries, while rare, do occur during gynecologic procedures. The expansion of laparoscopic and robotic pelvic surgical procedures increases the risk of ureteral injury from these procedures and suggests a role for minimally invasive approaches to the delayed repair of ureteral injuries. We present, to our knowledge, the first case of delayed robotic-assisted ureteral deligation and ureterolysis following iatrogenic ureteral injury occurring during a robotic abdominal hysterectomy. METHODS: We present a case report and review of the literature. RESULTS: A 57-year-old female underwent a seemingly uncomplicated robotic-assisted laparoscopic total abdominal hysterectomy and bilateral oophorectomy for symptomatic fibroids. On postoperative day 8, she presented with persistent right flank pain. Imaging studies revealed high-grade ureteral obstruction consistent with suture ligation of the right ureter. She underwent successful robotic-assisted ureteral deligation and ureterolysis. Her postoperative course was unremarkable, and she was discharged home on postoperative day 1 from the deligation. CONCLUSION: Robotic-assisted management of complications from urologic or gynecologic surgery is technically feasible. This can potentially preserve the advantages to the patient that are being seen from the initial less-invasive surgery.

Anatomic excision of anterior prostatic fat at radical prostatectomy: implications for pathologic upstaging.

INTRODUCTION: After exposure of the retropubic space, the surgeon commonly dissects the fat overlying the prostate and usually discards it. We have previously described the importance of dissecting this fat to completely visualize the dorsal venous complex (DVC) and prostatic apex. In this study, we describe a technique to dissect and remove the anterior prostatic fat pad (APF) and its anatomic and pathologic significance. TECHNICAL CONSIDERATIONS: After the retropubic space was prepared, we dissected the fat overlying the puboprostatic ligaments and the DVC to fully expose these structures. The superficial branch of the DVC was then transected, and the fat was dissected cephalad to the junction with the bladder. The fat was then further dissected laterally toward the lateral pelvic sidewall. Video analysis of the lateral dissection of the fat revealed a direct link to the obturator lymph node chain, where it was transected. Pathologic analysis demonstrated that 30 (14.7%) of 204 patients had one or more APF lymph nodes, of which four were positive for metastatic prostate cancer. The cancer of 3 of these 4 patients was upstaged as a result of the detection of these positive nodes. CONCLUSIONS: The dissection of the APF facilitates visualization of the apex and bladder neck. Anatomically, we have demonstrated that the APF contains lymph nodes approximately 15% of the time that are in communication with the obturator lymph node chain and DVC. We found that removal of the APF and its pathologic analysis can result in pathologic upstaging.

Culture requirements of prostatic epithelial cell lines for acinar morphogenesis and lumen formation in vitro: role of extracellular calcium.

BACKGROUND: Three-dimensional (3D) culture of benign prostatic epithelial cell lines can recapitulate acinar morphogenesis in vitro, but the broad applicability of this approach has not been described. The present studies examine the culture conditions important for prostatic acinar morphogenesis in vitro and the role of extracellular calcium in this process. METHODS: With optimized culture conditions, RWPE-1, pRNS-1-1, PZ-HPV-7, PNT1A, BPH-1, and PrEC were analyzed for their ability to undergo acinar morphogenesis in 3D culture and by immunoblotting. RWPE-1 cells were further examined for the effects of calcium on morphology, E-cadherin membrane localization and multicellular layering in 2D culture and for acinar morphogenesis, luminal apoptosis, and luminal filling in 3D. RESULTS: Cell lines grown in low-calcium medium have the ability to form acinar structures with lumens, which correlates with E-cadherin expression, but low calcium is not required for this process. Adding CaCl(2) to the medium strongly inhibits lumen formation, luminal apoptosis and induces luminal filling, and luminal filling is blocked by an interfering antibody. CONCLUSIONS: Optimized medium composition allows nearly all seeded RWPE-1 cells to undergo acinar morphogenesis, forming consistent structures representative of normal adult prostate glands. Low-calcium-containing medium appears selective for cells capable of undergoing acinar morphogenesis in vitro, and branching and luminal space within the acini are strongly influenced by extracellular calcium levels, likely through the actions of E-cadherin. These results provide important information about a relevant in vitro model with which to study prostate development and carcinogenesis and highlight the importance of extracellular calcium in regulating 3D morphology.

Robotic-assisted laparoscopic cystoprostatectomy for prostatic carcinosarcoma.

Carcinosarcoma of the prostate is a rare neoplasm with malignant epithelial and mesenchymal components. Herein, we report the case of a patient who underwent multiple transurethral resections of the prostate showing adenocarcinoma initially then carcinosarcoma. He underwent a robotic-assisted laparoscopic cystoprostatectomy, bilateral pelvic lymph node dissection, and ileal conduit urinary diversion and was discharged on postoperative day 7. Carcinosarcoma is discussed as an extremely rare malignancy of the prostate, with less than 50 cases reported in the literature. Robotic-assisted radical cystoprostatectomy is also discussed as a new procedure in minimally invasive surgery and as the first reported use for prostatic carcinosarcoma.

Reduced annexin II protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer.

CONTEXT: Annexin II is a calcium-dependent phospholipid-binding protein that plays a role in many cellular functions, including apoptosis, signal transduction, and cellular motility. The protein is strongly expressed in normal prostatic epithelial glands, but its expression in benign prostatic lesions has not been reported. Although commonly underexpressed in prostate cancer, the association of reduced expression with pathologic grade and stage is unknown. OBJECTIVE: To compare annexin II expression in benign prostatic lesions with expression in high-grade prostatic intraepithelial neoplasia and prostate cancer, as well as to correlate expression levels with pathologic grade and stage. DESIGN: A semi-quantitative assessment of annexin II expression was performed in radical prostatectomy specimens from 74 patients and prostate needle core biopsy specimens from 13 patients. Foci with normal prostatic glands, atrophic glands, basal cell hyperplasia, high-grade prostatic intraepithelial neoplasia, and prostatic adenocarcinoma were evaluated. RESULTS: Annexin II expression was present in more than 50% of glands in most (>85%) samples of benign prostatic epithelium, atrophic glands, and basal cell hyperplasia. In high-grade prostatic intraepithelial neoplasia, annexin II staining was markedly reduced in epithelial cells but not in basal cells. Annexin II was absent or focally present in moderately differentiated adenocarcinoma but was retained in poorly differentiated adenocarcinomas. CONCLUSIONS: Reduced annexin II expression may be a useful diagnostic biomarker to help identify small foci of moderately differentiated adenocarcinoma on needle core biopsy specimens since it is consistently expressed in benign prostatic glands. Re-expression of annexin II in poorly differentiated adenocarcinoma may provide prognostic information.