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to CcRCC lines. Activation of the mTORC1 complex, as measured by phospho-S6 levels, was comparable between TfRCC and CcRCC lines, as were levels of total MET. In contrast, phosphorylated MET and endogenous MET ligand (HGF) were undetectable in TfRCC lines, despite variable expression in CcRCC lines. LY294002 inhibition of Akt activation dramatically reduced proliferation of all TfRCC cell lines, with growth-IC50s of 10-20 M, and mTOR inhibition with sirolimus yielded a ⬎30% growth reduction in 4 of 5 TfRCC cell lines at concentrations of ⬍/⫽ 100 nM. MET inhibition with either PHA665752 or PF02341066 failed to suppress growth at concentrations (up to 1000 nM) well beyond the IC50 for these drugs reported in sensitive cell lines. CONCLUSIONS: The Akt-mTOR pathway is activated in TfRCC cell lines. This activation appears independent of MET signaling as TfRCC lines revealed no evidence of MET activation. Pharmacologic inhibition of Akt and mTOR but not MET effectively suppresses TfRCC growth in vitro, supporting a role for therapeutic targeting of the Akt-mTOR pathway in TfRCC patients. Source of Funding: Departmental
Pediatrics: Congenital Anomalies - Kidney & Ureter Moderated Poster Sunday, May 20, 2012
1:00 PM-3:00 PM
449 CAN WE ELIMINATE THE SCREENING VOIDING CYSTOURETHROGRAM IN CHILDREN WITH MULTICYSTIC DYSPLASTIC KIDNEY? Beth Drzewiecki*, Douglass Clayton, John Thomas, John Pope, Mark Adams, John Brock, Stacy Tanaka, Nashville, TN INTRODUCTION AND OBJECTIVES: Our understanding of both multicystic dysplastic kidney(MCDK) and vesicoureteral reflux(VUR) has increased significantly over the years and therefore management continues to evolve. While reflux nephropathy in a solitary kidney can be devastating, the natural history of VUR in MCDK is primarily that of resolution. The current guidelines regarding VUR do not address children with a solitary kidney. We sought to determine role of screening VCUG in patients diagnosed with MCDK. METHODS: We retrospectively reviewed the charts of all patients with a diagnosis of MCDK (ICD9 753.19) between January 1, 2000 and July 31, 2010. 210 patients were identified as having a diagnosis of MCDK and only 2 did not have a screening VCUG. Information including gender, screening VCUG, grade of reflux, location of reflux (contralateral vs ipsilateral), febrile UTI, resolution of VUR or surgical intervention, and indication for surgery was obtained. Kaplan-Meier survival analysis was performed to evaluate outcomes of contralateral reflux over time. RESULTS: A total of 208 children (54% male and 46% female) included in the analysis. Documented VUR on either side was found in 51 (25%) of patients. Contralateral VUR was found in 37 (18%) of children with MCDK, of whom 8 had bilateral VUR. Median follow up of patients with contralateral VUR was 30.1 months (range 6.2-97.7). Clinically significant VUR was seen in 3 patients (1.4%) as noted by nephropathy (1) and febrile UTI (2). Nine patients underwent surgical correction for contralateral VUR, one of whom had endoscopic correction only. Indications for surgery included nephropathy (1), febrile UTIs (2), and concern for reflux in solitary kidney (6). Resolution in the children observed was documented by radiologic study in 18, of whom 12 had high grade VUR(grade III-V). Median time to resolution was 16.5 months (range 10.6 to 53). On Kaplan-Meier analysis, there is an 80% likelihood of children not requiring surgical intervention for contralateral VUR at 48 months. CONCLUSIONS: Overall, 208 VCUGs were performed to detect clinically significant VUR in 1.4% of patients. Children with MCDK
and contralateral VUR have a low likelihood of febrile UTI and excellent chance of resolution of even high grade VUR. Abnormal post natal ultrasound should still warrant investigation for VUR. Parents should be cautioned on the risks of UTIs in a solitary kidney and that any febrile illness should warrant urinary evaluation for infection. Source of Funding: None
450 DISPARITIES AND LACK OF CONSENSUS IN THE MANAGEMENT OF CHILDREN WITH PRENATALLY DIAGNOSED MILD HYDRONEPHROSIS: A SURVEY ANALYSIS OF MANAGEMENT PRACTICE BY PEDIATRIC UROLOGISTS, RADIOLOGISTS AND MATERNAL FETAL MEDICINE SPECIALISTS. Vitor C. Zanetta*, Marc Cendron, Jeanne Chow, Boston, MA; Jeffrey B. Campbell, Aurora, CO; Anthony C.D. Herndon, Charlottesville, VA; Bryan Bromley, Thomas D. Shipp, Hiep T. Nguyen, Boston, MA INTRODUCTION AND OBJECTIVES: There are no clear guidelines on the management of mild hydronephrosis (MH). Due to variation in physician approach, it is difficult to analyze outcomes and to theorize the optimal management of these patients. We set out to determine the variability in the diagnosis and management of MH by pediatric urologists, pediatric radiologists, and maternal fetal medicine obstetricians (MFMs). METHODS: Online surveys were sent to mailing lists for national societies of each specialty. Demographic and practice information was recorded. Participants were then surveyed on their diagnosis of MH and their recommendations for antibiotic prophylaxis, work-up scheduling and imaging preferences. Moderate or severe hydronephrosis management was recorded for comparison. RESULTS: 125 pediatric urologists, 109 radiologists, and 311 MFMs responded to the survey. Urologists and radiologists were divided between Society for Fetal Urology criterion (SFU) and the use of anterior posterior pelvic diameter (APD) for determining hydronephrosis, while MFMs clearly preferred using APD. For postnatal evaluation, radiologists preferred to use a personal criterion, while urologists preferred the APD or SFU grading system. There was a wide variation of antibiotic prophylaxis use among urologists. Interestingly, less experience correlated with recommending prophylaxis. Regarding the use of VCUG/ RNC in patients with MH, both urologists and radiologists did not consistent in their recommendations. The optimal US follow up time for prenatal hydronephrosis also had poor agreement. Of note, all results contrasted with much higher agreement for moderate or severe hydronephrosis. CONCLUSIONS: There is little consensus between and within urologists, radiologists and obstetricians on the diagnosis and management of mild hydronephrosis. Uniform management guidelines need to be developed among specialists dealing with children with mild prenatal hydronephrosis. Source of Funding: None
451 DOWN SYNDROME DOES NOT INCREASE THE RISK OF UROLOGICAL ANOMALIES IN CHILDREN Bulent Onal*, Caio M. Oliveira, Jeanne S. Chow, Courtney K. Rowe, Hiep T. Nguyen, Boston, MA INTRODUCTION AND OBJECTIVES: Recent studies suggest that children with Down syndrome have an increased frequency of associated renal and urinary tract anomalies (RUTAs). These conclusions are complicated by the increased likelihood of incidentally discovered RUTAs in this population with a greater rate of radiological examinations. The aim of this study is to assess the rate of RUTAs in patients with Down syndrome who underwent radiologic examinations involving the urinary system and to determine the outcomes of both incidentally discovered and symptomatic RUTAs.
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METHODS: We retrospectively reviewed the records of 1,377 children seen at our institution since 1990 with Down syndrome. Patients who underwent imaging modalities that evaluated the urinary tract system with or without urologic indication were included into the study. The interval from birth until last ultrasound examination, regardless of diagnosis date, was accepted as the length of follow-up. Data was analyzed according to the indication for radiologic evaluation, and the results of follow-up were evaluated in patients with detected RUTAs. RESULTS: A total of 237 patients met the study inclusion criteria. The median age was 13.4 months. The indication for imaging was due to urologic symptoms in 111, whereas the urinary system was incidentally evaluated during radiologic examination done for another indication in 126 patients. While the rate of incidentally discovered RUTAs was 3%, the rate of symptomatic RUTAs was 40% (p⬍0.0001). Ureteropelvic junction obstruction-like hydronephrosis (UPJOH) was diagnosed in 29 patients, VUR in 12, PUV in four, megaureter in one, MCDK in one, and medullary sponge kidney in one patient. Median follow-up was 56.5 months (range 6 months to 9.6 years). During the followup of children with UPJOH and VUR, complete resolution was observed in 19 (65%) and 6 (50%) patients, respectively. CONCLUSIONS: While incidentally discovered RUTAs are found in 3% of Down syndrome patients undergoing radiologic evaluation, there is little clinical significance to discovering these abnormalities. Additionally, there is no indication that outcomes or resolution rates in children with Down syndrome are different from children with no associated genetic abnormality. Consequently, routine radiological evaluation of patients with Down syndrome is not clinically indicated and should not be performed to avoid unnecessary tests and cost. Source of Funding: None.
452 FENESTRATED CECOURETEROCOELE DECOMPRESSION WITH A DEFLUX® NEEDLE Martin Kaefer*, Indianapolis, IN; Ethan Franke, San Diego, CA INTRODUCTION AND OBJECTIVES: Endoscopic management of a cecoureterocele can be quite challenging. Transurethral incision can result in the distal lip of the incised ureterocele filling with voided urine, creating a valve type obstruction at the bladder neck. We describe a simple, inexpensive technique for fenestrating the ureterocele with a Deflux® needle in order to relieve obstruction, while avoiding the risk of post decompression bladder outlet obstruction and VUR. METHODS: A retrospective review of five consecutive patients with cecoureterocele was performed. The ureterocele was injected with radiographic contrast and subsequently punctured between 25 and 50 times with a Deflux® needle. Medical records were reviewed for preoperative radiographic and clinical data, operative description, and postoperative radiologic and clinical outcomes. RESULTS: Five patients underwent this procedure between January 2006 and November 2010. Average age at time of procedure was 30 days (range 4 -120 days). Average follow up was 3.1 years. All ureteroceles were associated with grade 3 or grade 4 hydronephrosis. The technique successfully decompressed the ureterocele in all cases. Hydronephrosis resolved in all cases. VCUG revealed no evidence of obstruction at the bladder neck in any patient. VUR into the ureter drained by the ureterocele was observed in only one of the five patients treated (20%). CONCLUSIONS: Our initial experience utilizing a Deflux® needle to decompress cecoureteroceles demonstates it to be highly effective in achieving upper tract drainage while minimizing the potential for VUR. The technique allows for complete decompression of the cecoureterocele while avoiding creation of a distal lip that could result in bladder neck obstruction. Source of Funding: None
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453 ROBOT-ASSISTED LAPAROSCOPIC PYELOPLASTY: MULTI-INSTITUTIONAL EXPERIENCE IN INFANTS Daniel I. Avery*, Thomas S. Lendvay, Seattle, WA; Katherine W. Herbst, Hartford, CT; Matthew C. Steele, Sean T. Corbett, C. D. Anthony Herndon, Charlottesville, VA; Christina Kim, Hartford, CT INTRODUCTION AND OBJECTIVES: Robot-assisted laparoscopic pyeloplasty (RALP) has been gaining acceptance among pediatric urologists. Over 300 have been described in the literature within pediatric series, but only one small single-center study evaluated the role of RALP in infants alone. We surveyed the experiences of multiple centers on the safety and efficacy of RALP in the infant population. METHODS: We reviewed the records of all RALP operations on patients less than 1 year of age conducted by 4 surgeons at 3 different institutions between April 2006 and August 2011. Pre-, peri-, and post-operative data were collected and analyzed. RESULTS: Forty-one infants with 43 ureteropelvic junction obstructions (UPJO) underwent RALP. Thirty-eight patients (92.7%) were diagnosed after prenatal ultrasound demonstrated hydronephrosis. The median age at surgery was 7.0 months (1-12) and the median weight was 8.2 kg (5.7-12.6). All surgeries reported minimal blood loss. One procedure was converted to pure laparoscopy due to robotic malfunction -the only operative complication in the group. Median surgical time was 231 minutes (150-345) with a slight downward trend over time approaching significance (p⫽0.063). Ureteral stents were placed in all procedures. Removal required a second anesthetic. One patient had an external drain. Forty-two of 43 patients had a Foley catheter which was removed prior to discharge. Thirty-four patients (81%) were discharged on post-operative day 1 (1-6). There were 3 post-operative complications: 1 ileus, 1 UTI, 1 port site hernia. Follow-up data is available for 36 patients representing 38 kidneys (3 await post-operative imaging and 2 were lost to follow-up). Median follow-up time was 19 months (1-53). Of the 38 repairs with post-operative imaging, 37 (97.3%) showed improvement or resolution of the hydronephrosis on renal ultrasound. There were 2 failures. One had worse drainage on renal scan 10 months after the surgery (despite improved ultrasound post-operatively). After balloon dilation he is currently doing well. The other had worsened hydronephrosis post-operatively on ultrasound; a renal scan showed that he had developed complete UPJO. He had a successful repeat RALP. CONCLUSIONS: RALP has become a viable surgical approach for the correction of pediatric UPJO. We show that the use of robotic assistance in infant pyeloplasty is not only safe but effective, with success rates comparable to open and laparoscopic series. Source of Funding: None
454 IDENTIFICATION OF POTENTIAL URINARY BIOMARKERS OF CLINICALLY SIGNIFICANT URETEROPELVIC JUNCTION OBSTRUCTION John W. Froehlich, Andrew C. Briscoe, Hanno Steen, Richard S. Lee*, Boston, MA INTRODUCTION AND OBJECTIVES: Identifying clinically significant kidney obstruction (UPJO) from non-significant hydronephrosis remains difficult. While excellent surgical treatment of UPJO exists, better non-invasive diagnostic tests are needed. In this work, a thorough proteomic analysis of pediatric urine from the obstructed kidney, the normal contralateral kidney, and healthy controls identifies several putative biomarkers which may aid in patient stratification. METHODS: Samples were obtained from age- and sexmatched controls, and UPJO patients undergoing pyeloplasty. UPJO urine from both the obstructed kidney (HUK) and the bladder (HUB) representing the contralateral normal kidney was obtained. Samples were processed by a spin-filter based protocol. Proteins were isolated and quantified and equal amounts were digested with trypsin. Peptides were isobarically labeled, mixed and separated by isoelectric focusing.