Curtis J. Clark

Malfunction of the da Vinci Robotic System During Robot-Assisted Laparoscopic Prostatectomy: An International Survey

PURPOSE To determine how urologists manage technical malfunction of the Da Vinci robotic system during robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS A web-based survey was sent to urologists performing RARP. The survey questions were related to the stage of operation during which robotic malfunction occurred, management of malfunctions, and most common types of robotic malfunction. In addition, data were collected concerning surgical volume and training. RESULTS One hundred (56.8%) of the 176 responding surgeons had experienced an irrecoverable intraoperative malfunction. Eighty respondents experienced mechanical failure before starting RARP, of which 46 (57.5%) rescheduled, 15 (18.8%) performed an open radical approach, 12 (15%) performed standard laparoscopic prostatectomy, and 4 (4.9%) docked another robot. Sixty-three respondents experienced mechanical failure before starting urethrovesical anastomosis, of which 26 (41.2%) converted to an open procedure, 20 (31.7%) converted to standard laparoscopy, 10 (15.8%) finished with one less arm, and 3 (4.7%) aborted the procedure. Thirty-two respondents experienced malfunction before completion of the anastomosis, of which 20 (62.5%) converted to standard laparoscopy, while 12 (37.5%) converted to open surgery. Fellowship trained surgeons were more likely to complete the prostatectomy using standard laparoscopy (P = 0.05). No significant differences existed between surgeons performing a high volume or low volume of prostatectomies in regard to management of malfunctions. CONCLUSION Intraoperative breakdown of the Da Vinci robot is uncommon, but patients should be counseled preoperatively and a plan devised on how breakdown will be managed. Intracorporeal suturing skills allow conversion to a pure laparoscopic approach, if necessary. Consequently, standard laparoscopic suturing skills should remain in the residency curriculum.

Efficacy of c-Met inhibitor for advanced prostate cancer

BackgroundAberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR) signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC). Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer.MethodsWe tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression.ResultsWe demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration.ConclusionsThe c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer.

Evaluation of Three Laparoscopic Modalities: Robotics versus Three-Dimensional Vision Laparoscopy versus Standard Laparoscopy

PURPOSE Standard laparoscopy has undergone many recent advances with the advent of three-dimensional visual systems and robotic surgical systems. In evaluating the usefulness of these new systems, it is difficult to objectively measure their advantages in the operating room. Therefore, we designed a trial using three different laparoscopic modalities to evaluate the strengths and weaknesses of each modality. MATERIALS AND METHODS Twenty-seven subjects were entered into the study. Three different laparoscopic modalities were tested. These included standard laparoscopy with two-dimensional cameras, the 3Di Endosite visual system, and the daVinci Robotic Surgical System. A standard laparoscopic trainer was utilized and testing consisted of three different tasks: peg transfer, ring manipulation, and cannulation. RESULTS Of the 27 subjects, 16 (60%) reported some degree of laparoscopic experience. The number of pegs transferred with standard laparoscopy and the Endosite 3Di system was significantly greater than with the robot. The number of errors committed during the peg transfer test and the amount of time required was significantly lower with the Endosite 3Di system compared to the robot. Subjects completed the ring manipulation task significantly faster with the robot, but the number of errors committed was no different among the three modalities. Subjects were able to complete the cannulation task with their dominant hand significantly faster with the robot compared to the Endosite 3Di system or standard laparoscopy, and committed fewer errors using the robot compared to standard laparoscopy. CONCLUSIONS This study showed improved performance using three-dimensional optics on some tasks, but not a significant improvement in overall results. Three-dimensional vision does appear beneficial during performance of some complex tasks. The wrist-like action of the robot improved performance on some tasks, while the lack of tactile feedback likely was a source of errors on other tasks.

Differentiation Associated Changes in Gene Expression Profiles of Interstitial Cystitis and Control Urothelial Cells

PURPOSE We evaluated gene expression profiles after inducing differentiation in cultured interstitial cystitis and control urothelial cells. MATERIALS AND METHODS Bladder biopsies were taken from patients with interstitial cystitis and controls, that is women undergoing surgery for stress incontinence. Primary cultures were grown in keratinocyte growth medium with supplements. To induce differentiation in some plates the medium was changed to Dulbeccos modified Eagles minimal essential medium-F12 (Media Tech, Herndon, Virginia) with supplements. RNA was analyzed with Affymetrix(R) chips. Three patients with nonulcerative interstitial cystitis were compared with 3 controls. RESULTS After inducing differentiation 302 genes with a described function were altered at least 3-fold in interstitial cystitis and control cells (p <0.01). Functions of the 162 up-regulated genes included cell adhesion (eg claudins, occludin and cingulin), urothelial differentiation, the retinoic acid pathway and keratinocyte differentiation (eg skin cornified envelope components). The 140 down-regulated transcripts included genes associated with basal urothelium (eg p63, integrins beta4, alpha5 and alpha6, basonuclin 1 and extracellular matrix components), vimentin, metallothioneins, and members of the Wnt and Notch pathways. When comparing interstitial cystitis control cells after differentiation, only 7 genes with a described function were altered at least 3-fold (p <0.01). PI3, SERPINB4, CYP2C8, EFEMP2 and SEPP1 were decreased, and AKR1C2 and MKNK1 were increased in interstitial cystitis cases. CONCLUSIONS Differentiation associated changes occurred in interstitial cystitis and control cells. Comparing interstitial cystitis vs control cases revealed few differences. This study may have included patients with interstitial cystitis and minimal urothelial deficiency, and/or we may have selected cells that were most robust in culture. Also, the abnormal urothelium in interstitial cystitis cases may be due to post-translational changes and/or to the bladder environment.

Urinary Tract Infection in Children: When to Worry

Urinary tract infection (UTI) is a frequent diagnosis in children who are referred to the urologist. Although most infections will resolve without complication after appropriate treatment, a wide array of potential complicating factors exists, which can make difficult the rapid resolution of a UTI. Clinical scenarios involving these factors require a high index of suspicion and prompt initiation of appropriate therapy.

Quantitative Ultrasound Renal Parenchymal Area Correlates With Renal Volume and Identifies Reflux Nephropathy

PURPOSE Studies show that renal volume on magnetic resonance imaging correlates with differential function and is decreased in children with vesicoureteral reflux diagnosed after urinary tract infection. We examined the correlation between ultrasound renal parenchymal area and magnetic resonance imaging volume to determine whether quantitative ultrasound renal parenchymal area might be a reliable, less costly and less invasive substitute for renal magnetic resonance imaging volume. MATERIALS AND METHODS To determine the correlation of ultrasound renal parenchymal area with magnetic resonance imaging, we identified 82 children with primary vesicoureteral reflux who underwent renal magnetic resonance imaging and ultrasound. Magnetic resonance imaging volume was compared with ultrasound renal parenchymal area, renal length and calculated ellipsoid volume. To determine the correlation of ultrasound renal parenchymal area with reflux grade, ultrasound renal parenchymal area was examined in 96 children with reflux and urinary tract infection, and in 52 with reflux without urinary tract infection. Linear regression and multivariate analysis were performed to find the relationship between ultrasound renal parenchymal area and reflux grade. RESULTS The correlation of ultrasound renal parenchymal area with magnetic resonance imaging volume was superior to that of renal length and calculated ellipsoid volume (r(2) = 0.90 vs 0.83 and 0.84, respectively). Hydronephrosis did not affect the correlation. On multiple regression analysis in children with reflux and urinary tract infection higher reflux grade correlated with decreased ultrasound renal parenchymal area (p = 0.0016). In children with reflux without urinary tract infection reflux grade did not correlate with decreased ultrasound renal parenchymal area (p = 0.47). CONCLUSIONS Ultrasound renal parenchymal area correlates closely with magnetic resonance imaging derived 3-dimensional renal volume and is capable of detecting progressive renal area loss in patients with reflux and urinary tract infection. More studies are necessary to verify whether data from more invasive tests, such as renal magnetic resonance imaging and dimercapto-succinic acid scan, may be attained from ultrasound renal parenchymal area alone.

Sacral Nerve Stimulator Revision Due to Somatic Growth

PURPOSE Sacral nerve modulation is a Food and Drug Administration approved treatment for refractory urgency, frequency, urge incontinence and nonobstructive urinary retention in adults. The sparse literature on sacral nerve modulation in children focuses on its initial efficacy in patients with neurogenic bladder and dysfunctional elimination. We describe our initial experience with sacral nerve modulation and the phenomenon of growth spurts associated with lead malfunction that necessitates revision. MATERIALS AND METHODS After receiving institutional review board approval we retrospectively reviewed the charts of pediatric patients who underwent sacral nerve modulation surgery at our institution. Charts were examined for patient demographics, subjective success, the need for further surgery and success after revision. RESULTS Four patients underwent sacral nerve modulation at an average age of 12.1 years. All patients reported initial success, defined as greater than 50% symptom improvement. Subsequently 3 patients required a total of 5 revisions due to lead malfunction with an average of 1.5 years between surgeries. In those requiring revision the average somatic growth between revisions was 8.1 cm. Return of efficacy was reported after each revision. All patients had functioning nerve stimulators in place and continued to have a positive subjective response. CONCLUSIONS The sparse data on sacral nerve modulation in children shows efficacy and safety similar to those in adults. Somatic growth may be associated with lead malfunction and require surgical revision. We report a small series showing that revision can be done successfully and safely. Informed consent for sacral nerve modulation in pediatric patients should include a discussion of somatic growth as a possible cause of lead malfunction necessitating revision.

Hand-Assisted Laparoscopic Partial Nephrectomy Without Formal Collecting System Closure: Perioperative Outcomes in 104 Consecutive Patients

BACKGROUND AND PURPOSE Laparoscopic partial nephrectomy (LPN) paralleling open techniques, particularly closure of the collecting system, can be technically challenging for the novice laparoscopist. We describe operative results and complications of a single surgeon, retrospectively reviewed series using a simplified method of hand assistance and a fibrin glue patch for hemostasis without formal collecting system closure. PATIENTS AND METHODS We identified 104 consecutive patients between September 2003 and January 2009 who underwent hand-assisted laparoscopic partial nephrectomy (HALPN). Our technique involves routine hilar clamping after isolation of the tumor and mobilization of the kidney. After resection of the mass, a fibrin glue patch is placed within the surgical defect and secured with bolstering sutures. No attempt is made to suture the collecting system, nor are ureteral catheters placed when the collecting system is entered during resection of the tumor. RESULTS Mean tumor size was 2.8 cm (median 2.5 cm, range 0.7-7.0 cm). With hilar clamping, warm ischemia time averaged 24.5 minutes (range 11-39 min). Estimated blood loss averaged 220 mL (range 50-1500 mL), and five (4.8%) patients received transfusions either intraoperatively or postoperatively. Urine leak occurred in 1.9% (n=2) of patients overall and 4.3% (2/47) of patients with documented collecting system entry. Both urine leaks resolved with conservative management only. CONCLUSIONS HALPN without formal collecting system closure is a safe and effective technique with similar urine leak and transfusion rates compared with other series. This technique may allow more urologists to perform minimally invasive partial nephrectomy or to do so with potentially shorter ischemia times.

Radiation Exposure During Pediatric Videourodynamics

PURPOSE Videourodynamics is useful for evaluating and treating neurological disorders in children. Traditional urodynamic parameters can be obtained while simultaneous visualization of the urinary system can reveal anatomical anomalies. This additional information comes at the cost of radiation exposure to the child. We characterized radiation exposure from videourodynamics. MATERIALS AND METHODS We reviewed all recent videourodynamic studies and recorded patient demographics, urological diagnoses, physical attributes, total fluoroscopy time, total radiation exposure in mGy, bladder capacity and the number of filling cycles performed. Multivariate linear regression was used to identify patient factors that independently influenced total radiation exposure. RESULTS A total of 64 videourodynamic studies were performed in 34 female and 28 male patients with a mean age of 8.6 years (95% CI 7.2-10.0). The most common diagnosis was neurogenic bladder in 40 patients, although 49 had multiple diagnoses. Mean total fluoroscopy time was 1.8 minutes (95% CI 1.4-2.1) and mean total radiation exposure was 10 mGy (95% CI 7.5-13.3). On multivariate linear regression patient weight and bladder capacity were the only independent predictors of total radiation exposure. CONCLUSIONS Videourodynamics entail significant radiation exposure. Patient weight and bladder capacity were independent predictors of total radiation exposure. Physician awareness of radiation exposure may result in the judicious use of fluoroscopy and aid in counseling parents on the risk of videourodynamics. Further research is needed to quantify organ specific doses of radiation due to medical imaging in children and the associated cancer risks.

The leucine zipper putative tumor suppressor 2 protein LZTS2 regulates kidney development

Background: The LZTS2 is a novel β-catenin-interacting protein, and its role in development and tumorigenesis is unknown. Results: Lzts2 KO mice show severe kidney and urinary tract developmental defects, including renal/ureteral duplication, hydroureter, and hydronephrosis. Conclusion: LZTS2 plays a critical role in kidney and urinary tract development. Significance: A novel mechanism by which LZTS2 regulates β-catenin mediated nephrogenesis is implicated. Members of the leucine zipper putative tumor suppressor (LZTS) family play crucial roles in transcription modulation and cell cycle control. We previously demonstrated that LZTS2 functions as a novel β-catenin-interacting protein and represses β-catenin-mediated transcription on T-cell factor/lymphoid enhancing factor. Here, we investigate the biological role of LZTS2 using newly established Lzts2 KO mice. Homozygosity for loss-of-function of the Lzts2-targeted allele resulted in severe kidney and urinary tract developmental defects, including renal/ureteral duplication, hydroureter, and hydronephrosis, which were visible prenatally. Altered ureteric bud outgrowth was identified in Lzts2 null embryos. Further analysis indicated that β-catenin subcellular localization was altered in fibroblasts isolated from Lzts2 null embryos. In addition, Wnt growth factor-induced β-catenin-mediated transcriptional activity was increased in Lzts2 null fibroblasts, suggesting a direct role for Lzts2 in the Wnt signaling pathway. These data demonstrate a critical role of LZTS2 in renal development and implicate LZTS2 as a critical regulator of β-catenin-mediated nephrogenesis.