John P. Gearhart

The anatomy of the pelvis in the exstrophy complex

We compared computerized tomography scans of the pelvis of twenty-four patients who had exstrophy of the bladder with scans of age-matched controls in order to analyze the pelvic deformity that accompanies the variably severe manifestations of this condition. The patients who had classic exstrophy of the bladder were found to have a mean of 12 degrees of external rotation of the posterior aspect of the pelvis on each side, retroversion of the acetabula, a mean additional 18 degrees of external rotation and 30 per cent shortening of the pubic rami, and progressive diastasis of the symphysis pubis. The foot-progression angle demonstrated 20 to 30 degrees of external rotation beyond the normal limits seen in early childhood, but this improved with age. The patients who had exstrophy of the cloaca and the bladder not only had all of these pelvic deformities to a greater degree but also had asymmetry of measured parameters between the right and left sides of the pelvis, malformation of the sacro-iliac joints, and occasional dislocation of the hip. An understanding of the pelvic anatomy that accompanies exstrophy is essential when corrective approaches are planned. Such an understanding will improve the rate of success of both closure of the bladder and control of urinary continence postoperatively.

IN VITRO FERTILIZATION IS ASSOCIATED WITH AN INCREASED RISK OF HYPOSPADIAS

PURPOSE The purpose of this study was to determine if there is an increased incidence of hypospadias in male offspring conceived by in vitro fertilization (IVF). MATERIALS AND METHODS A retrospective institutional chart review from 1988 to 1992 and data from the Maryland Birth Defects Registry were statistically analyzed to assess the risk of hypospadias with IVF. RESULTS The data for the 5-year period indicated a 5-fold increased risk of hypospadias after IVF, with an incidence of approximately 1.5% in the IVF group and 0.3% in the control group. The only recognized difference between the groups was maternal progesterone administration in the IVF group but the cause of the increased risk of hypospadias was unknown. The distribution of hypospadias severity was similar in both groups. CONCLUSIONS Male newborns conceived by IVF have a 5-fold increased risk of hypospadias, which may be related to maternal progesterone administration, or other maternal or fetal endocrine abnormalities that may or may not be related to infertility. Health care providers should be aware of this risk so that they can properly counsel infertile couples seeking assisted reproduction by IVF technology.

Endoscopic injection of glutaraldehyde cross-linked bovine dermal collagen for correction of vesicoureteral reflux.

From November 1986 through May 1989, a Food and Drug Administration approved investigational study was done to assess the safety and efficacy of glutaraldehyde cross-linked bovine dermal collagen in the endoscopic treatment of vesicoureteral reflux. Over-all, 57 patients (92 ureters) were treated. The majority of ureters (68.5%) had grade II to III/V vesicoureteral reflux (international classification). One treatment was given in 61.4% of the patients, while 33.3% required 2 and 5.3% required 3 treatments. Nonduplicated/primarily refluxing ureters comprised 68.5% of the total, while 13% were duplex/primarily refluxing and 18.5% were surgical failures. The procedures were performed on an outpatient basis in all but 3 patients. Patients were evaluated by voiding cystourethrogram and renal/bladder sonography before and after treatment at 1 month and 1 year. Cure at 1 month after the last treatment was achieved in 75% of the ureters. Among the ureters cured at 1 month the cure persisted in 79% at 1 year after treatment. Cure at 1 year was achieved in 65% of all ureters evaluated, regardless of the status at 1 month. Procedure-related morbidity was minimal and there were no adverse reactions to the implant substance. Thus, glutaraldehyde cross-linked bovine dermal collagen appears to be safe and effective in the endoscopic treatment of vesicoureteral reflux.

A COMBINED VERTICAL AND HORIZONTAL PELVIC OSTEOTOMY APPROACH FOR PRIMARY AND SECONDARY REPAIR OF BLADDER EXSTROPHY

PURPOSE We describe a new combined horizontal and vertical pelvic osteotomy procedure for bladder exstrophy. MATERIALS AND METHODS A total of 36 patients with the bladder exstrophy complex underwent this procedure during a 3-year period (8 primary and 18 secondary bladder closures, and 6 at bladder neck reconstruction). RESULTS There were no instances of dehiscence and only a minor bladder prolapse in 1 patient with cloacal exstrophy. Two patients had a transient femoral nerve palsy and there was 1 superficial pin infection. Urological complications included symptomatic urinary tract infections in 5 patients, acute epididymitis in 1 and bladder calculi in 2. CONCLUSIONS This new osteotomy procedure is of great benefit in initial or repeat closure of bladder exstrophy and may help in eventually achieving continence.

Liposomal Delivery of Heat Shock Protein 72 Into Renal Tubular Cells Blocks Nuclear Factor-κB Activation, Tumor Necrosis Factor-α Production, and Subsequent Ischemia-Induced Apoptosis

Abstract— Heat shock protein 72 (HSP72) is a stress-inducible protein capable of protecting a variety of cells from toxins, thermal stress, and ischemic injury. The cytoprotective role and mechanism of action of HSP72 in renal cell ischemic injury remain unclear. To study this, HSP72 was introduced (liposomal transfer) or induced (thermal stress, 43°C×1 hour) in renal tubular cells (LLC-PK1) with Western blot confirmation. Cells were subjected to simulated ischemia 24 hours after liposomal HSP72 transfer or thermal stress, and the effect of HSP72 on nuclear factor-&kgr;B (NF-&kgr;B) activation (electrophoretic mobility shift assay and immunohistochemistry), I&kgr;B&agr; production (Western blot), postischemic tumor necrosis factor-&agr; (TNF-&agr;) production (RT-PCR), and apoptosis (TUNEL assay) were determined. In separate experiments, the role of TNF-&agr; in apoptosis was determined (anti-TNF-&agr; neutralizing antibody). Results demonstrated that both liposomal transfer of HSP72 and thermal induction of HSP72 prevented NF-&kgr;B activation and translocation, TNF-&agr; gene transcription, and subsequent ischemia-induced renal tubular cell apoptosis. Furthermore, TNF-&agr; neutralization also inhibited ischemia-induced renal tubular cell apoptosis. These results indicate that liposomal delivery of HSP72 inhibits ischemia-induced renal tubular cell apoptosis by preventing NF-&kgr;B activation and subsequent TNF-&agr; production. Further elucidation of the mechanisms of HSP-induced cytoprotection may result in therapeutic strategies that limit or prevent ischemia-induced renal damage.

Delayed Bladder Rupture after Augmentation Enterocystoplasty

Delayed bladder perforation with peritonitis following augmentation enterocystoplasty in children with spina bifida is a serious and potentially life-threatening complication. Our experience with 4 such cases is presented. All patients had spina bifida with a neuropathic bladder and they had undergone augmentation enterocystoplasty with a tubular colonic segment of large bowel as part of an undiversion procedure. All patients were being managed with intermittent self-catheterization. The interval from augmentation enterocystoplasty until presentation ranged from 6 months to 3 years. Diagnosis was delayed in all cases, including 3 in which cystogram studies were normal despite findings of extravasation of urine at exploration. In 1 patient generalized sepsis developed with the respiratory distress syndrome and, subsequently, she died.

Penile Length in Adulthood after Exstrophy Reconstruction

PURPOSE We attempted to determine whether the penis in adulthood after exstrophy reconstruction is short because of a congenital defect in the size of the corpora cavernosa. MATERIALS AND METHODS Pelvic magnetic resonance imaging was performed on 10 men who underwent exstrophy reconstruction in childhood, and 10 age and race matched controls. Measurements of penile and pelvic anatomy were compared. RESULTS The corpora cavernosa in men after exstrophy reconstruction were shorter than normal. Dividing total corporeal length into an anterior and posterior segment revealed that the anterior segment was short but the posterior segment attached to the pubic ramus was normal. However, the diameter of the posterior corporeal segment was greater than in controls. Although diastasis of the symphysis pubis increased the intersymphyseal and intercorporeal distances, the angle between the corpora cavernosa was unchanged, presumably because the corporeal bodies were separated in a parallel fashion. CONCLUSIONS After exstrophy reconstruction the penis is short in adulthood, at least partially due to a congenital deficiency of corporeal tissue. Since diastasis of the pubic symphysis and chordee decrease penile visibility, approximation of the pubic symphysis and procedures to straighten the penis may improve cosmesis. However, because the corpora cavernosa are short, after exstrophy reconstruction the penis will always be shorter than normal in adulthood.

Anterior Innominate Osteotomies For Failure or Late Closure of Bladder Exstrophy

The bony pelvis was analyzed in 12 patients undergoing a further operation after initial bladder closure. Of the patients 5 had undergone a prior posterior osteotomy. All patients had wide diastasis of the pubis (average 5.5 cm.). In 9 of these patients late closure or reclosure of a failed initial bladder repair was done and 3 underwent a repeat bladder neck reconstruction. In all patients a new procedure, anterior iliac osteotomy with internal or external fixation, was performed. This procedure provides increased mobility of the pubis and increased correction. It avoids turning of the patient while under anesthesia for repeat preparation and in most cases postoperative traction is not needed. There were no instances of dehiscence, nonunion or infection. Three cases of transient femoral palsy were noted. All patients had a normal gait 4 months postoperatively. The mobility obtained after anterior osteotomy allows for excellent approximation. In view of evidence that approximation of the pubis improves closure and eventual continence results, we believe that osteotomies, even when repeated, are useful in revision surgery if there is bony diastasis.

Urogynaecological and obstetric issues in women with the exstrophy‐epispadias complex

The authors from Copenhagen write about their 15‐year consistent strategy in the treatment of antenatally suspected PUJ obstruction. The group deals with this controversial subject in some detail, and they outline data which they feel are helpful for urologists giving advice to parents about the advisability of having the condition treated by operative or conservative means.

Perinatal exposure to genistein alters reproductive development and aggressive behavior in male mice

Exposure to endocrine disrupting chemicals adversely affects reproductive development and behavior in males. The goal of this study was to determine if exposure to genistein, an isoflavone found in soy, during early periods of sex differentiation alters reproductive development and behavior in male mice. Female C57BL/6 mice were fed a phytoestrogen-free diet supplemented with 0, 5 or 300 mg/kg of genistein throughout gestation and lactation. Anogenital distance (AGD) and body mass of male offspring was measured weekly from postnatal days 2-21, timing of preputial separation was assessed at puberty, and in adulthood, reproductive organ masses, sperm and testosterone production, and reproductive and aggressive behaviors were assessed. Exposure to genistein resulted in smaller AGD are reduced body mass, with the low-dose diet exerting a greater effect. Timing of preputial separation, adult reproductive behavior, sperm concentrations and testosterone production were not influenced by genistein treatment at either dose. Aggressive behaviors were decreased, whereas defensive behaviors were increased, in males that received the low-dose genistein diet. Exposure to genistein during critical periods of sex differentiation results in concurrent and persistent demasculinization in male mice. Phenotypic and behavioral abnormalities induced by genistein showed a non-monotonic response, where treatment with a low dose exerted a greater effect than treatment with a high dose of genistein. Given the popularity of soy infant formulas, the influence isoflavone exposure on reproductive and behavioral health in boys and men should be considered.