526 the prostatic utricle: an under-recognized cause of morbidity in boys with both hypospadias and...

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526 THE PROSTATIC UTRICLE: AN UNDER-RECOGNIZED CAUSE OF MORBIDITY IN BOYS WITH BOTH HYPOSPADIAS AND NORMAL EXTERNAL GENITALIA Stanley Kogan*, Bronx, NY INTRODUCTION AND OBJECTIVES: Pediatric presentations of a prostatic utricle have received only scant attention. Though recog- nized with increased frequency in boys with hypospadias little is de- scribed about incidence and potential morbidity in boys with normal external genitalia. Our experience with symptomatic utricles in boys with both situations led us to review the frequency, causes for morbidity and indications and results of surgical repair. METHODS: Initial retrospective review of 64 patients with hy- pospadias seen between 2003-2006 was done to determine frequency of lower urinary tract studies (VCUG and/or cystoscopy) and utricle identification. Children with genetic disorders of sexual differentiation were excluded. This initial cohort was extended to a larger group with hypospadias, also identifying a group of 23 boys with normal external genitalia presenting with various signs and symptoms who were found to have an unsuspected utricle. Symptomatology was the indication for evaluation in the latter group contrasting with the hypospadias group mostly investigated because of hypospadias presence alone. Method- ology for identification and choices of surgical treatment and outcomes were reviewed. RESULTS: Of 64 patients only 25 (37.5%) underwent an inves- tigative study, mostly because of symptomatic urinary infection or bacteriuria. Utricle frequency in this group was 9.4% (6). Three (50%) required surgical excision with excellent outcome allowing their hypo- spadias repair to proceed. Results in the more expanded hypospadias group confirmed these findings with increased rates of investigation and identification noted. Boys with normal external genitalia all required surgical treatment since the symptoms resulted from the utricle alone. Penile pain with voiding, hematuria, epididymitis and urinary infection were the most common causes. At surgery considerable variation in utricle size and location of vas deferens insertion were noted. CONCLUSIONS: The prostatic utricle should be considered as a potential cause of morbidity in boys with both normal external geni- talia as well as those with hypospadias. Endoscopic or radiological evaluation should be undertaken in all boys with proximal hypospadias and those with distal hypospadias with associated symptoms or signs. Boys with normal external genitalia with persisting signs or symptoms not explained by radiological investigations should undergo cystoscopy as an unidentified unsuspected utricle may be the underlying cause. Utricle size should determine the best route for surgical intervention. Source of Funding: None 527 HIGH INCIDENCE OF HYPOSPADIAS IN GRAND-SONS OF WOMEN EXPOSED TO DIETHYSTILBESTROL (DES) DURING PREGNANCY: A NATIONWIDE MULTIGENERATIONAL STUDY Nicolas Kalfa*, F Paris, MO Soyer-Gobillard, RB Galifer, JP Daures, C Sultan, Montpellier, France INTRODUCTION AND OBJECTIVES: DES was prescribed for 2-8 millions of pregnancies until 1970s with the mistaken belief that it would prevent miscarriage. Unfortunately, this synthetic estrogen was found to have harmful effects. Prenatal DES exposure has been shown to increase the incidence of genital malformation in males, especially hypospadias. More intriguingly, DES-exposed mice have raised suspi- cion on a transgenerational effect, questioning whether the harmful effects of DES may be transmitted to subsequent generations. The aim of this work was to evaluate the impact of prenatal DES treatment on grandsons of women treated with DES during pregnancy. METHODS: A nationwide epidemiological study in collabora- tion with a French association of DES treated women was conducted. 529 families, representing 1180 pregnancies, were included. In 1000 pregnancies an exposition to DES was reported. 180 pregnancies were conducted without DES. The second generation study included 465 boys. Mutational analysis of androgen receptor (AR), 5 alpha reductase (5aR) and MAMLD1 genes in hypospadiac boys was performed. Other maternal environmental expositions were investigated. RESULTS: First generation: the incidence of hypospadias was low among boys non-exposed to DES in utero (0/180). On the opposite, the incidence of the malformation in the exposed boys was 3.57% (isolated hypospadias, severe n12, non severe n4). Second gen- eration: the incidence of hypospadias in boys born from mothers or fathers non-exposed to DES was low (n0/360). In boys born from exposed fathers, the incidence of hypospadias was low too (n0/8). On the opposite, boys born from DES daughters exhibited hypospadias in 6.1% of cases (severe n4, non severe n2). No mutation of the AR, 5aR and MAMLD1 were identified. Other professional exposition of the mother was not significant during pregnancy. CONCLUSIONS: Beyond confirming the impact of prenatal exposure to synthetic estrogens on the development of male genitalia, these results are cause for concern. They show a strong transgenera- tional effect of DES in boys of the second generation. DES sons are unlikely to predispose their own sons to hypospadias, whereas DES- related pathology of reproductive structures in DES daughters may interfere with normal fetal development during pregnancy. Source of Funding: University grant PHRC UF8270 528 THE UTILITY OF UROFLOWMETRY IN THE LONG-TERM FOLLOW UP OF DISTAL HYPOSPADIAS REPAIR Richard Ashley*, Ahmed BaniHani, Julia Barthold, T. Ernesto Figueroa, Wilmington, DE INTRODUCTION AND OBJECTIVES: Uroflowmetry has been utilized as an objective measure of successful distal hypospadias repair. However, no guidelines exist for how to use uroflow data in order to identify those patients who need repeat intervention. We sought to determine if this test could be used as a predictive tool for which patients would require a repeat operation. METHODS: A retrospective chart review was conducted to identify patients with at least 36 months of follow-up after distal hypo- spadias repair. Additional inclusion criteria included successful potty- training and one complete uroflow study with post-void residual. Uro- flow parameters for each child were compared to the previously published Miskolc nomograms. Univariate and multivariate analyses were performed to determine factors associated with the need for repeat intervention with p0.05 considered significant RESULTS: A total of 329 patients underwent distal hypospa- dias repair from 2000-2006. 107 patients met inclusion criteria for the study and had median follow-up of 63 months (range 36-146mo). The median age at surgery was 7mo (range 3-149mo) and median age at post-operative uroflow was 5.7y (range 3-17yr). Several hypospadias repair techniques were utilized: tubular incised plate (TIP, 12/107, 11%), Theirsh-Duplay (TD, 44/107, 41%), Mathieu (Ma, 31/107, 29%), sleeve advancement (SA, 11/107, 10%), MAGPI (M, 9/107, 8%). When the entire cohort was analyzed and the Qmax was compared to the published norms on the Miskolc nomograms, 38% (41/107) of the patients had Qmax below the 5th percentile. However, only 13% e208 THE JOURNAL OF UROLOGY Vol. 183, No. 4, Supplement, Sunday, May 30, 2010

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526THE PROSTATIC UTRICLE: AN UNDER-RECOGNIZED CAUSEOF MORBIDITY IN BOYS WITH BOTH HYPOSPADIAS ANDNORMAL EXTERNAL GENITALIA

Stanley Kogan*, Bronx, NY

INTRODUCTION AND OBJECTIVES: Pediatric presentationsof a prostatic utricle have received only scant attention. Though recog-nized with increased frequency in boys with hypospadias little is de-scribed about incidence and potential morbidity in boys with normalexternal genitalia. Our experience with symptomatic utricles in boyswith both situations led us to review the frequency, causes for morbidityand indications and results of surgical repair.

METHODS: Initial retrospective review of 64 patients with hy-pospadias seen between 2003-2006 was done to determine frequencyof lower urinary tract studies (VCUG and/or cystoscopy) and utricleidentification. Children with genetic disorders of sexual differentiationwere excluded. This initial cohort was extended to a larger group withhypospadias, also identifying a group of 23 boys with normal externalgenitalia presenting with various signs and symptoms who were foundto have an unsuspected utricle. Symptomatology was the indication forevaluation in the latter group contrasting with the hypospadias groupmostly investigated because of hypospadias presence alone. Method-ology for identification and choices of surgical treatment and outcomeswere reviewed.

RESULTS: Of 64 patients only 25 (37.5%) underwent an inves-tigative study, mostly because of symptomatic urinary infection orbacteriuria. Utricle frequency in this group was 9.4% (6). Three (50%)required surgical excision with excellent outcome allowing their hypo-spadias repair to proceed. Results in the more expanded hypospadiasgroup confirmed these findings with increased rates of investigationand identification noted. Boys with normal external genitalia all requiredsurgical treatment since the symptoms resulted from the utricle alone.Penile pain with voiding, hematuria, epididymitis and urinary infectionwere the most common causes. At surgery considerable variation inutricle size and location of vas deferens insertion were noted.

CONCLUSIONS: The prostatic utricle should be considered asa potential cause of morbidity in boys with both normal external geni-talia as well as those with hypospadias. Endoscopic or radiologicalevaluation should be undertaken in all boys with proximal hypospadiasand those with distal hypospadias with associated symptoms or signs.Boys with normal external genitalia with persisting signs or symptomsnot explained by radiological investigations should undergo cystoscopyas an unidentified unsuspected utricle may be the underlying cause.Utricle size should determine the best route for surgical intervention.

Source of Funding: None

527HIGH INCIDENCE OF HYPOSPADIAS IN GRAND-SONS OFWOMEN EXPOSED TO DIETHYSTILBESTROL (DES) DURINGPREGNANCY: A NATIONWIDE MULTIGENERATIONAL STUDY

Nicolas Kalfa*, F Paris, MO Soyer-Gobillard, RB Galifer, JP Daures,C Sultan, Montpellier, France

INTRODUCTION AND OBJECTIVES: DES was prescribed for2-8 millions of pregnancies until 1970s with the mistaken belief that itwould prevent miscarriage. Unfortunately, this synthetic estrogen wasfound to have harmful effects. Prenatal DES exposure has been shownto increase the incidence of genital malformation in males, especiallyhypospadias. More intriguingly, DES-exposed mice have raised suspi-cion on a transgenerational effect, questioning whether the harmfuleffects of DES may be transmitted to subsequent generations. The aimof this work was to evaluate the impact of prenatal DES treatment ongrandsons of women treated with DES during pregnancy.

METHODS: A nationwide epidemiological study in collabora-tion with a French association of DES treated women was conducted.529 families, representing 1180 pregnancies, were included. In 1000pregnancies an exposition to DES was reported. 180 pregnancies were

conducted without DES. The second generation study included 465boys. Mutational analysis of androgen receptor (AR), 5 alpha reductase(5aR) and MAMLD1 genes in hypospadiac boys was performed. Othermaternal environmental expositions were investigated.

RESULTS: First generation: the incidence of hypospadias waslow among boys non-exposed to DES in utero (0/180). On the opposite,the incidence of the malformation in the exposed boys was 3.57%(isolated hypospadias, severe n�12, non severe n�4). Second gen-eration: the incidence of hypospadias in boys born from mothers orfathers non-exposed to DES was low (n�0/360). In boys born fromexposed fathers, the incidence of hypospadias was low too (n�0/8). Onthe opposite, boys born from DES daughters exhibited hypospadias in6.1% of cases (severe n�4, non severe n�2). No mutation of the AR,5aR and MAMLD1 were identified. Other professional exposition of themother was not significant during pregnancy.

CONCLUSIONS: Beyond confirming the impact of prenatalexposure to synthetic estrogens on the development of male genitalia,these results are cause for concern. They show a strong transgenera-tional effect of DES in boys of the second generation. DES sons areunlikely to predispose their own sons to hypospadias, whereas DES-related pathology of reproductive structures in DES daughters mayinterfere with normal fetal development during pregnancy.

Source of Funding: University grant PHRC UF8270

528THE UTILITY OF UROFLOWMETRY IN THE LONG-TERMFOLLOW UP OF DISTAL HYPOSPADIAS REPAIR

Richard Ashley*, Ahmed BaniHani, Julia Barthold, T. ErnestoFigueroa, Wilmington, DE

INTRODUCTION AND OBJECTIVES: Uroflowmetry has beenutilized as an objective measure of successful distal hypospadiasrepair. However, no guidelines exist for how to use uroflow data in orderto identify those patients who need repeat intervention. We sought todetermine if this test could be used as a predictive tool for whichpatients would require a repeat operation.

METHODS: A retrospective chart review was conducted toidentify patients with at least 36 months of follow-up after distal hypo-spadias repair. Additional inclusion criteria included successful potty-training and one complete uroflow study with post-void residual. Uro-flow parameters for each child were compared to the previouslypublished Miskolc nomograms. Univariate and multivariate analyseswere performed to determine factors associated with the need forrepeat intervention with p�0.05 considered significant

RESULTS: A total of 329 patients underwent distal hypospa-dias repair from 2000-2006. 107 patients met inclusion criteria for thestudy and had median follow-up of 63 months (range 36-146mo). Themedian age at surgery was 7mo (range 3-149mo) and median age atpost-operative uroflow was 5.7y (range 3-17yr). Several hypospadiasrepair techniques were utilized: tubular incised plate (TIP, 12/107,11%), Theirsh-Duplay (TD, 44/107, 41%), Mathieu (Ma, 31/107, 29%),sleeve advancement (SA, 11/107, 10%), MAGPI (M, 9/107, 8%). Whenthe entire cohort was analyzed and the Qmax was compared to thepublished norms on the Miskolc nomograms, 38% (41/107) of thepatients had Qmax below the 5th percentile. However, only 13%

e208 THE JOURNAL OF UROLOGY� Vol. 183, No. 4, Supplement, Sunday, May 30, 2010