2
200 THE JOURNAL OF UROLOGY ® Vol. 179, No. 4, Supplement, Sunday, May 18, 2008 with outcome and (2) there was no clear evidence that PSAV improves the predictive accuracy of a single PSA value alone. Source of Funding: Cancer Research UK, Boxer Family Fellowship, NCI (SPORE). 571 A SIGNIFICANT CHANGE IN PROGRESSION FREE PROBABILITY FOLLOWING RADICAL PROSTATECTOMY IS MORE COMMON IN AFRICAN-AMERICANS THAN IN CAUCASIANS Melissa A Laudano*, Mark J Mann, Ketan K Badani, Chad Ritch, Manisha Desai, Mitchell C Benson, James M McKiernan. New York, NY. INTRODUCTION AND OBJECTIVE: The incidence of prostate cancer (CaP) is 60% higher in African-American (AA) men compared to white men, and AA men have been shown to have more lethal disease. Cancer related mortality rates for AA compared to whites are 65.1 and 26.7 per 100,000, respectively. Many nomograms exist to predict survival outcomes using pre-treatment clinical parameters and post-treatment pathological parameters. Race may be an important factor affecting their predictive ability. This study evaluates whether pre-operative nomograms underestimate progression free probability (PFP) when compared to post-radical prostatectomy (RP) probilities in AA men. METHODS: Using the Columbia Comprehensive Clinical Database of Urologic Oncology, a retrospective analysis of 3,663 men who underwent RP for CaP from 1988 to 2007 was conducted. Kattan nomograms were used to calculate pre-treatment and post-RP 5-year PFP. The difference between the two nomogram scores was found and or more when compared to pre-treatment nomogram prediction. No recurrence. worse post-RP PFP, 57.6% had no change, and 15.9% had improved post-RP PFP. In whites, 13.8% had worse post-RP PFP, 64.5% had no change, and 21.7% had improved post-RP PFP. When comparing the mean change in probability, AA men had a mean difference of +5.4 (CI 1.0, 9.8) signifying a worsened post-RP PFP. In contrast, white men had a mean difference of -3.3 (CI -4.4, -2.3) signifying slight improvement 2.3 times the odds of having a worse (vs. improved or static) post-RP PFP than whites (OR 2.3, CI 1.4, 3.4). CONCLUSIONS: In our experience, AA men are more likely than whites to have worse post-RP 5-year PFP compared to their pre- RP predictions. Further research is needed to evaluate whether this discrepancy is attributable to more aggressive disease, inadequate treatment values in AA men. Regardless, this data may allow urologists to provide more accurate counseling to AA patients prior to RP. Source of Funding: None Pediatrics: Congenital Anomalies-Kidney & Ureter Podium Session 15 Sunday, May 18, 2008 3:30 - 5:30 pm 572 THE Gly691Ser MUTATION IN RET IS ASSOCIATED WITH PRIMARY VESICOURETERAL REFLUX IN THE FRENCH- CANADIAN POPULATION IN QUEBEC Yaoming Yang, Anne-Marie Houle, Julien Letendre*, Andrea Richter. Montreal, QC, Canada. INTRODUCTION AND OBJECTIVE: Primary vesicoureteral abnormality in children. While the genetic nature of pVUR is well established, both the inheritance pattern and the genes responsible are unknown. During urological organogenesis, a receptor tyrosine kinase, RET mediates signalling pathways known to be required and and elongation of the distal ureter and formation of the vesicoureteric RET signalling, or of RET itself may cause pVUR, we screened the members. population referred to the Urology Clinic of Sainte-Justine Hospital recruited only patients from french speaking families who were born in Canada. pVUR was diagnosed by a voiding cystourethrogram and other urological malformations were ruled out. As part of the normal clinical protocol, we screened all siblings of the currently followed probands and. A questionnaire to identify parents with pVUR approved by the institutional review board of our institution was administered. Genomic DNA was extracted from all family members’ blood samples. A sequencing-based candidate gene approach was used to screen compared to unaffected controls. RESULTS: We recruited 70 (312 family members) families with at least one member affected by pVUR. We found that 83 of 118 patients (index and siblings) carried the single nucleotide polymorphism (SNP) rs1799939, a variation that results in a Gly691Ser mutation in Ret. A nonpolar glycine is changed to a polar serine residue that is a predicted phosphorylation site of protein kinase C. The allelic frequency of this SNP is dramatically increased from 0.145 in control to 0.360 in patients, parallel comparison of six other RET SNPs. Our analysis of transfected interact and associate with a 75~80 kD tyrosine phosphorylated cellular protein, an event not seen with wild type Ret. CONCLUSIONS: Our study demonstrates that the Gly691Ser Ret mutation is associated with pVUR and may be a genetic origin of this condition in the French-Canadian population. Source of Funding: This study was supported by Kidney Foundation of Canada operating grant (to AM.H. and A.R.) and the fund from le Centre de Recherche de CHU-Sainte-Justine. 573 THE URODYNAMIC AND HISTOLOGIC CHANGES IN STERILE RABBIT VESICOURETERAL REFLUX MODEL Min Ki Baek*, Sung Hyun Paick, Seong Jin Jeong, Soo Woong Kim, Hwang Choi. Seoul, Republic of Korea. INTRODUCTION AND OBJECTIVE: We aimed to investigate bladder and renal pelvic pressure at different infusion rates with different levels of bladder fullness in surgically induced sterile rabbit vesicoureteral were used in this study. Ten animals were served as control group, 15 underwent open and closure of bladder as sham operation group, and ureter. Three weeks later, urodynamic study was performed in the 3 groups. Histologic examination was also performed. RESULTS: At low infusion rate, the renal pelvic pressures in the sham operation and the control group were stable, but the renal pelvic pressure in the VUR group was stable until the bladder capacity approached 80% fullness and then slightly increased. At high infusion rate, the renal pelvic pressures of the sham operation and the control group were stable until the bladder capacity approached 80% fullness and then slightly increased, and the renal pelvic pressure in the VUR group was steadily increased from the bladder capacity approached 40% fullness. The renal pelvic pressure was increased along with bladder contraction during voiding phase only in the VUR group. No histologic change of the renal cortex was observed in the sham operation and the control group. However, focal thinning of the tubular epithelium and

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200 THE JOURNAL OF UROLOGY® Vol. 179, No. 4, Supplement, Sunday, May 18, 2008

with outcome and (2) there was no clear evidence that PSAV improves the predictive accuracy of a single PSA value alone.

Source of Funding: Cancer Research UK, Boxer FamilyFellowship, NCI (SPORE).

571A SIGNIFICANT CHANGE IN PROGRESSION FREE PROBABILITY FOLLOWING RADICAL PROSTATECTOMY IS MORE COMMON IN AFRICAN-AMERICANS THAN IN CAUCASIANSMelissa A Laudano*, Mark J Mann, Ketan K Badani, Chad Ritch, Manisha Desai, Mitchell C Benson, James M McKiernan. New York, NY.

INTRODUCTION AND OBJECTIVE: The incidence of prostate cancer (CaP) is 60% higher in African-American (AA) men compared to white men, and AA men have been shown to have more lethal disease. Cancer related mortality rates for AA compared to whites are 65.1 and 26.7 per 100,000, respectively. Many nomograms exist to predict survival outcomes using pre-treatment clinical parameters and post-treatment pathological parameters. Race may be an important factor affecting their predictive ability. This study evaluates whether pre-operative nomograms underestimate progression free probability (PFP) when compared to post-radical prostatectomy (RP) probilities in AA men.

METHODS: Using the Columbia Comprehensive Clinical Database of Urologic Oncology, a retrospective analysis of 3,663 men who underwent RP for CaP from 1988 to 2007 was conducted. Kattan nomograms were used to calculate pre-treatment and post-RP 5-year PFP. The difference between the two nomogram scores was found and

or more when compared to pre-treatment nomogram prediction. No

recurrence.

worse post-RP PFP, 57.6% had no change, and 15.9% had improved post-RP PFP. In whites, 13.8% had worse post-RP PFP, 64.5% had no change, and 21.7% had improved post-RP PFP. When comparing the mean change in probability, AA men had a mean difference of +5.4 (CI 1.0, 9.8) signifying a worsened post-RP PFP. In contrast, white men had a mean difference of -3.3 (CI -4.4, -2.3) signifying slight improvement

2.3 times the odds of having a worse (vs. improved or static) post-RP PFP than whites (OR 2.3, CI 1.4, 3.4).

CONCLUSIONS: In our experience, AA men are more likely than whites to have worse post-RP 5-year PFP compared to their pre-RP predictions. Further research is needed to evaluate whether this discrepancy is attributable to more aggressive disease, inadequate

treatment values in AA men. Regardless, this data may allow urologists to provide more accurate counseling to AA patients prior to RP.

Source of Funding: None

Pediatrics: Congenital Anomalies-Kidney & Ureter

Podium Session 15

Sunday, May 18, 2008 3:30 - 5:30 pm

572THE Gly691Ser MUTATION IN RET IS ASSOCIATED WITH PRIMARY VESICOURETERAL REFLUX IN THE FRENCH-CANADIAN POPULATION IN QUEBECYaoming Yang, Anne-Marie Houle, Julien Letendre*, Andrea Richter. Montreal, QC, Canada.

INTRODUCTION AND OBJECTIVE: Primary vesicoureteral

abnormality in children. While the genetic nature of pVUR is well established, both the inheritance pattern and the genes responsible

are unknown. During urological organogenesis, a receptor tyrosine kinase, RET mediates signalling pathways known to be required and

and elongation of the distal ureter and formation of the vesicoureteric

RET signalling, or of RET itself may cause pVUR, we screened the

members.

population referred to the Urology Clinic of Sainte-Justine Hospital

recruited only patients from french speaking families who were born in Canada. pVUR was diagnosed by a voiding cystourethrogram and other urological malformations were ruled out. As part of the normal clinical protocol, we screened all siblings of the currently followed probands and. A questionnaire to identify parents with pVUR approved by the institutional review board of our institution was administered. Genomic DNA was extracted from all family members’ blood samples. A sequencing-based candidate gene approach was used to screen

compared to unaffected controls. RESULTS: We recruited 70 (312 family members) families with

at least one member affected by pVUR. We found that 83 of 118 patients (index and siblings) carried the single nucleotide polymorphism (SNP) rs1799939, a variation that results in a Gly691Ser mutation in Ret. Anonpolar glycine is changed to a polar serine residue that is a predicted phosphorylation site of protein kinase C. The allelic frequency of this SNP is dramatically increased from 0.145 in control to 0.360 in patients,

parallel comparison of six other RET SNPs. Our analysis of transfected

interact and associate with a 75~80 kD tyrosine phosphorylated cellular protein, an event not seen with wild type Ret.

CONCLUSIONS: Our study demonstrates that the Gly691Ser Ret mutation is associated with pVUR and may be a genetic origin of this condition in the French-Canadian population.

Source of Funding: This study was supported by Kidney Foundation of Canada operating grant (to AM.H. and A.R.) and the fund from le Centre de Recherche de CHU-Sainte-Justine.

573THE URODYNAMIC AND HISTOLOGIC CHANGES IN STERILE RABBIT VESICOURETERAL REFLUX MODELMin Ki Baek*, Sung Hyun Paick, Seong Jin Jeong, Soo Woong Kim, Hwang Choi. Seoul, Republic of Korea.

INTRODUCTION AND OBJECTIVE: We aimed to investigate

bladder and renal pelvic pressure at different infusion rates with different levels of bladder fullness in surgically induced sterile rabbit vesicoureteral

were used in this study. Ten animals were served as control group, 15 underwent open and closure of bladder as sham operation group, and

ureter. Three weeks later, urodynamic study was performed in the 3 groups. Histologic examination was also performed.

RESULTS: At low infusion rate, the renal pelvic pressures in the sham operation and the control group were stable, but the renal pelvic pressure in the VUR group was stable until the bladder capacity approached 80% fullness and then slightly increased. At high infusion rate, the renal pelvic pressures of the sham operation and the control group were stable until the bladder capacity approached 80% fullness and then slightly increased, and the renal pelvic pressure in the VURgroup was steadily increased from the bladder capacity approached 40% fullness. The renal pelvic pressure was increased along with bladder contraction during voiding phase only in the VUR group. No histologic change of the renal cortex was observed in the sham operation and the control group. However, focal thinning of the tubular epithelium and

Vol. 179, No. 4, Supplement, Sunday, May 18, 2008 THE JOURNAL OF UROLOGY® 201

demonstrated that there was no difference in the mean diameter, cellular height of distal tubules and the extracellular matrix volume among the 3 groups. However, changes in the mean tubular diameter and

by subanalysis according to the renal pelvic pressure. CONCLUSIONS: The changing pattern of renal pelvic

pressure in the VUR group was affected by bladder infusion rate, which suggests that VUR mechanism depends on other than only anatomical

cortical change coupled with evidence that the renal cortical changes were corresponded to animals with higher renal pelvic pressure.

Source of Funding: Clinical Research Institute, Seoul National University Hospital.

574IMMUNOHISTOCHEMICAL EXAMINATION OF THE REGION BENEATH THE DISTAL URETER OF THE HUMAN FETUS AND MOUSE: INSIGHTS INTO THE SUCCESS OF ENDOSCOPIC TREATMENT OF VESICOURETERAL REFLUXEllen Shapiro*, Cathy Mendelsohn, Miriam Cremer, Hongying Huang. New York, NY.

INTRODUCTION AND OBJECTIVE: Success of endoscopic

cases, decreasing the width of the ureter may not be necessary for the

in lineage studies of mice, we reported the fate of ureteral and bladder muscle progenitors and showed that the trigone is formed primarily from bladder muscle with a more minor contribution from ureteral longitudinal

that the intercalation of ureteral and bladder muscle may be critical

examines the histology of the region just beneath the distal ureter which is a target region for bioinjectables used in the endoscopic treatment

METHODS: The ureterovesical junction including the distal ureter of adult mouse (vibratome sections) and human fetuses (sagittal sections 4 µ) ages 18-22 wks was stained with antibodies to smooth

(mouse sections). RESULTS: In the mouse and human fetus, there is a large

wedge of lamina propria (LP) just beneath the distal ureter. (Fig 1)

Longitudinal ureteral SM appears to interdigitate with the adjacent SM component of the LP as well as contribute to the formation of the trigone.

CONCLUSIONS: Studies of human fetus and adult mouse suggest that the distal ureter may have attachments to the LP and

interdigitations not only to the bladder SM forming the trigone but also to the adjacent SM of the LP. Creation of a mound within the subureteric LP using bioinjectables leads to foreign body reaction which effectively

between these two structures.

Source of Funding: None

575PROSPECTIVE COMPARATIVE STUDY OF POLYDIMETHYLSILOXANE VS HYALURONIC ACID INJECTION FOR TREATMENT OF VESICOURETERAL REFLUXKatherine Moore*, Stephane Bolduc. Quebec, QC, Canada.

INTRODUCTION AND OBJECTIVE: Endoscopic treatment

commercialised in Canada for VUR.METHODS: Between January 2003 and December 2006,

111 patients (25 males, 86 females) followed for primary VUR were prospectively enrolled in a comparative study to be endoscopically treated with subureteral injection of either polydimethylsiloxane

grade was I in 17 ureters, II in 39, III in 54, IV in 16 and V in 5. 52 ureters

and V in 2. Surgical indications were breakthrough urinary tract infection

a single surgeon on an outpatient basis, with the patient under general anesthesia. Patients were followed with renal ultrasonography and voiding cystourethrography 3 months after the surgery.

RESULTS: Based on their characteristics, both groups

corrected in 119 (91%) of 131 ureteral units. However, complete resolution

Obstruction was found in 2 ureters injected with polydimethylsiloxane and in 1 with hyaluronic acid. Univariate and multivariate analyses were

rate between the two groups except the type of product used. CONCLUSIONS: Subureteral injection of polydimethylsiloxane

success rate than hyaluronic acid injection. The rate of resolution

groups due to the inclusion of high grade VUR. The lower cost of polydimethylsiloxane makes it an interesting product to use for the correction of VUR.

Source of Funding: None

576A COMPARISON OF CALCIUM HYDROXYLAPATITE (COAPTITE) AND DEXTRANOMER/HYALURONIC ACID (DEFLUX) FOR THE ENDOSCOPIC TREATMENT OF VURIlene Y Wong*, William A Kennedy. Stanford, CA.

INTRODUCTION AND OBJECTIVE: Currently, only one FDA approved agent for endoscopic treatment of VUR exists, namely

globally, including calcium hydroxylapatite (Coaptite), which has been shown in trials to have up to 75% success rate for the treatment of VUR,and which has recently been FDA approved for urologic use in the United States for treatment of urinary incontinence. Currently there exists no