Richard W. Grady

COMPLETE PRIMARY REPAIR OF EXSTROPHY

PURPOSE The surgical correction of bladder exstrophy to achieve continence with voiding remains a challenging problem for the urologist. Since 1989 we have performed complete primary repair for exstrophy based on the concept that the primary defect of bladder and cloacal exstrophy is anterior herniation. Thus, the bladder and urethra must be treated as a single unit to move them posteriorly into the pelvis. We present this technique. MATERIALS AND METHODS From 1989 to 1997, 18 patients with bladder exstrophy and 6 with cloacal exstrophy underwent complete primary repair of exstrophy. This procedure was done on day 1 of life in 18 patients. Mean followup is 44 months (range 4 months to 8 years). RESULTS At a median followup of 48 months 4 boys and 4 girls have volitional voiding after complete primary repair of bladder exstrophy, 21 patients have continent intervals and 2 boys void with continent intervals after complete primary repair of cloacal exstrophy. No patient has had a loss of renal function in this series. Postoperative complications included urethrocutaneous fistula formation in 2 cases. No patient had primary closure dehiscence. CONCLUSIONS The rate of urinary continence achieved with complete primary repair compares favorably to that of staged repair for exstrophy. Complete primary repair also minimizes the number of surgical procedures required to achieve urinary continence and potentiates bladder neck function that permits bladder cycling in year 1 of life. The complication rates of these techniques are significantly lower than those reported in previous series of primary closure of exstrophy.

Hypospadias in Washington State: Maternal Risk Factors and Prevalence Trends

Objective. Maternal risk factors for hypospadias are poorly defined, and there is debate about temporal trends in hypospadias prevalence. We examined select maternal characteristics as possible risk factors for hypospadias among male offspring and evaluated yearly prevalence rates in Washington State. Methods. We performed a population-based, case-control study using linked birth-hospital discharge data from Washington State for 1987–1997 and prevalence data for 1987–2002. All cases of hypospadias were identified on the basis of International Classification of Diseases, Ninth Revision, codes from the birth hospitalization (N = 2155). Five control subjects were randomly selected for each case subject from the remaining singleton births, frequency matched according to year of birth (N = 10775). Maternal and infant characteristics were ascertained from the birth certificate. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Yearly prevalence was determined by dividing the total number of hypospadias cases by the number of male singleton live births for each year. Results. The risk of delivering an affected male infant increased with advancing maternal age; relative to women <20 years of age, those >40 years of age were at greatest risk (OR: 1.70; 95% CI: 1.17–2.48). Infants of nonwhite women were generally at decreased risk. Infants born to women with preexisting diabetes mellitus were at greater risk than those born to women without diabetes (OR: 2.18; 95% CI: 1.03–4.60); however, this was not observed for infants born to women with gestational diabetes. The birth prevalence of hypospadias in 2002 was 5.0 cases per 1000 male births, not significantly different from that in 1987. Conclusion. Older maternal age, white race, and preexisting diabetes were associated with increased risk of hypospadias among male offspring. The prevalence of hypospadias in Washington State did not increase significantly between 1987 and 2002.

TLR4-mediated expulsion of bacteria from infected bladder epithelial cells

Uropathogenic Escherichia coli invade bladder epithelial cells (BECs) by direct entry into specialized cAMP regulated exocytic compartments. Remarkably, a significant number of these intracellular bacteria are subsequently expelled in a nonlytic and piecemeal fashion by infected BECs. Here, we report that expulsion of intracellular E. coli by infected BECs is initiated by the pattern recognition receptor, Toll-like receptor (TLR)4, after activation by LPS. Also, we reveal that caveolin-1, Rab27b, PKA, and MyRIP are components of the exocytic compartment, and that they form a complex involved in the exocytosis of bacteria. This capacity of TLR4 to mediate the expulsion of intracellular bacteria from infected cells represents a previously unrecognized function for this innate immune receptor.

Long-Term Followup of Complete Primary Repair of Exstrophy: The Seattle Experience

PURPOSE Since 1989, we have used the complete primary repair of exstrophy surgical technique to reconstruct the genitourinary system of children born with the exstrophy-epispadias complex based on the assumption that this complex represents a malformation. We initially reported using this technique in 1999. We now report a longer term followup of this initial group as well as surgical outcomes in a larger group of children who have undergone this repair for classic bladder exstrophy. MATERIALS AND METHODS Since 1989, we have prospectively followed 39 children who underwent the complete primary repair of exstrophy technique to construct classic bladder exstrophy. Median followup in the original group of patients that we reported in 1999 is 106 months. Median followup in the entire series is 58 months. RESULTS Of boys and girls 4 years or older 74% have achieved daytime continence with volitional voiding. Of boys and girls 20% and 43%, respectively, have achieved primary urinary continence without the need for bladder neck reconstruction. An additional 18% of boys and girls achieved continence with only bladder neck injection following complete primary repair of exstrophy. Complications developed in 7 of the 39 children (18%) in the entire series. CONCLUSIONS Urinary continence has been consistently achieved with this form of exstrophy repair. Primary continence without the need for further reconstruction is possible. The results of this patient series have caused us to modify the complete primary repair of exstrophy technique in an effort to improve the rate of primary urinary continence.

Metastatic Adenocarcinoma After Augmentation Gastrocystoplasty

PURPOSE Augmentation gastrocystoplasty has been proposed as an alternative to enterocystoplasty because of potential benefits, including decreased risk of mucus production, stone formation and urinary tract infections. Although cancer has rarely been reported in this patient population, it is a well recognized potential risk of all augmentation cystoplasties. To define better the risk of malignancy associated with gastric augmentation and the appropriate surveillance protocol for these patients, we describe our experience in 2 patients with metastatic adenocarcinoma following gastrocystoplasty. MATERIALS AND METHODS We retrospectively reviewed the charts of all patients who had undergone augmentation gastrocystoplasty between 1990 and 1994. Of the 72 patients identified 2 were diagnosed with a primary malignancy arising from the augmented bladder. Charts were reviewed for medical history, clinical outcomes and pathology. RESULTS Two patients were identified with a primary bladder malignancy after gastrocystoplasty. Both patients had metastatic disease at initial presentation. Neither patient had a history of gross hematuria, recurrent urinary tract infections or pain before initial presentation. Mean patient age at augmentation was 5.5 years. Mean age at diagnosis of malignancy was 19.5 years, with a mean time from augmentation of 14 years. CONCLUSIONS Although the risk of bladder cancer is low after gastric augmentation, the effects may be life threatening. Therefore, we advocate routine annual surveillance with cystoscopy, bladder biopsy and upper tract imaging in all patients who have undergone augmentation gastrocystoplasty.

Histology of the urethral plate: Implications for hypospadias repair

PURPOSE We define the histology of the urethral plate in boys with hypospadias. MATERIALS AND METHODS Subepithelial biopsies of the urethral plate were obtained in 17 boys, including 13 with distal and 4 with penoscrotal hypospadias. Ventral penile curvature was noted in 5 cases. Specimens were evaluated by 7 light microscopy after hematoxylin and eosin staining. RESULTS All biopsies demonstrated well vascularized connective tissue comprised of smooth muscle and collagen. There was no evidence of fibrous bands or dysplastic tissue. CONCLUSIONS The urethral plate consists of epithelium overlying connective tissue. We found no histological evidence of fibrous cords historically considered responsible for chordee.

Laparoscopic and histologic evaluation of the inguinal vanishing testis

OBJECTIVES Visual inspection of the spermatic cord vessels and vas deferens during laparoscopy now frequently determines further treatment. We set out to explore the implications of atretic spermatic cord vessels and vas deferens entering the inguinal ring, a finding noted on laparoscopic examination in some patients with a nonpalpable testis, and that we refer to as the inguinal vanishing testis. METHODS We reviewed our series of 35 patients with nonpalpable testes with regard to the laparoscopic, surgical, and histopathologic findings of the involved gonadal structures. RESULTS We noted atretic vessels and vas deferens entering the inguinal ring in 14 patients in this series. All 14 patients underwent open inguinal exploration. Histopathologic findings revealed fibrosis and hemosiderin deposits alone in 13 patients. One specimen had a microscopic focus of residual seminiferous tubules. No specimen contained dysgenetic gonadal tissue. CONCLUSIONS We submit that patients with inguinal vanishing testes do not need to undergo inguinal exploration to remove residual testicular tissue. Only rarely will viable seminiferous tubules be found, so the risk of malignant degeneration is remote. The histopathologic findings suggest that the inguinal vanishing testis occurs secondary to a vascular accident in utero or in the neonatal period.

Comparison of the Learning Curve and Outcomes of Robotic Assisted Pediatric Pyeloplasty

PURPOSE We compared the learning curve and outcomes in children undergoing robotic assisted laparoscopic pyeloplasty during the initiation of a robotic surgery program compared to the benchmark of open pyeloplasty. MATERIALS AND METHODS The records of our first consecutive 33 children undergoing robotic assisted laparoscopic pyeloplasty from 2006 to 2009 were retrospectively reviewed and compared to those of age and gender matched children who underwent open repair done by senior faculty surgeons before the initiation of our robotic surgery program. We compared operative time, complications, postoperative pain, length of stay and surgical success for 2 surgeons who adopted the robotic approach at an academic teaching institution. RESULTS We found no significant differences in length of stay, pain score or surgical success at a median followup of 16 months. The number of complications was similar and they tended to be early and technical in the robotic assisted laparoscopic pyeloplasty group. Overall average operative time was 90 minutes longer (38%) for robotic assisted laparoscopic pyeloplasty (p <0.004). When evaluated chronologically, there was evidence of a learning curve. After 15 to 20 robotic cases overall operative times for robotic assisted laparoscopic cases was consistently within 1 SD of our average open pyeloplasty time with no significant difference in overall operative time (p = 0.23). Of the decrease in overall operative time 70% was due to decreased pyeloplasty time rather than peripheral time. CONCLUSIONS There was similar safety and efficacy with robotic assisted laparoscopic pyeloplasty, although complications tended to be technical and early in our initial experience. Operative time decreased with experience and after 15 to 20 cases it was similar to that of open pyeloplasty with similar outcomes and surgical success.

Augmentation Cystoplasty Rates at Children’s Hospitals in the United States: A Pediatric Health Information System Database Study

PURPOSE We identified augmentation cystoplasty rates in children with spina bifida at childrens hospitals enrolled in the Pediatric Health Information System database. MATERIALS AND METHODS The Pediatric Health Information System database tabulates demographic and diagnostic patient data from 35 childrens hospital centers in the United States. Between October 1999 and September 2004 we extracted data on 0 to 19-year-old patients with International Classification of Diseases-9 diagnosis codes for spina bifida. The International Classification of Diseases-9 procedure code for augmentation cystoplasty was cross-referenced with these patients to determine the total number of patients with augmentation, total population augmentation rates and individual institution rates of bladder augmentation. RESULTS Staff at enrolled pediatric medical centers submitted inpatient data accounting for 9,059 beds servicing an aggregate metropolitan population of 82 million individuals. In the 5-year period 12,925 unique spina bifida patient encounters were identified, including 665 patients who underwent augmentation cystoplasty. The mean 5-year institutional number of augmentations performed in children with spina bifida was 20 (range 1 to 121) and the mean annual number of augmentations performed per institution was 4. The overall augmentation rate at 33 hospitals contributing data for the full years 2000 to 2003 was 5.4% (range 0.5% to 16.3%, p <0.0001). The male-to-female ratio of those who underwent augmentation was 1:1.2. Median length of stay in children with augmentation was 7 days (mean 9). The median age of children with augmentation was 10.4 years, that is 11.3 years in boys and 9.8 years in girls. The difference in mean age was statistically significant (p <0.003). At institutions where 10 or more augmentations were performed in 5 years (mean 27) mean patient age at operation was 10.1 years. This was significantly younger than the mean patient age of 12.3 years at hospitals where fewer than 10 augmentations (mean 5) were done in 5 years (p <0.05). CONCLUSIONS Clinical management for neurogenic bladder conditions has evolved to emphasize nonoperative management. Several studies suggest that aggressive early intervention improves bladder compliance and may protect renal function. However, results from the Pediatric Health Information System database demonstrate no change in augmentation rates during this time and they demonstrate significant interinstitutional variability. To our knowledge this represents the largest series of augmentation cystoplasty in children with spina bifida to date.

Newborn exstrophy closure and epispadias repair.

Abstract Over the last 150 years, bladder exstrophy has undergone a transition from a primarily nonsurgically treated disease to a disease treated by urinary diversion or staged repair and now, possibly, primary newborn reconstruction. Our enthusiasm for primary reconstruction arises because of its potential to simplify the management of this disorder and optimize the return of normal bladder function for these patients. As with most new concepts, the evolution of our primary reconstruction techniques could not have been achieved without the prior efforts of others. Other surgeons such as H. H. Young and J. Ansell have shown us the possibility of achieving urinary continence with primary newborn exstrophy closure without sacrificing renal function, but the results have been inconsistent in the past. Staged reconstruction for bladder exstrophy demonstrates the possibility to achieve consistent successful rates of continence in these patients. However, multiple surgical procedures are required to attain this success. The preliminary results of our series of primary bladder exstrophy closures has encouraged us to perform it for all neonates referred to our institution with bladder exstrophy as well as to use it as part of staged reconstructive efforts for patients who have undergone primary surgical procedures for exstrophy elsewhere. We are hopeful and optimistic that newborn primary exstrophy closure performed as described herein will produce consistent rates of urinary continence and allow normal voiding function as well.