Laurence S. Baskin

Changing concepts of hypospadias curvature lead to more onlay island flap procedures

From 1987 through 1992, 1,109 primary hypospadias operations were performed at our hospital, of which 374 (33%) were onlay island flap procedures. In contrast, from 1982 to 1987 only 66 of 657 primary hypospadias repairs (10%) were onlay island flaps. The increase in this type of repair stems from the observation that in most cases of hypospadias the urethral plate is not the cause of penile curvature. Intraoperative artificial erection after skin take down revealed that only 50 of the 374 patients (13%) still had a significant bend. After experience demonstrated that the residual bend was not due to a fibrous urethral plate, but rather to a generally mild (20 to 30 degree) corporeal disproportion, correction was achieved by dorsal tunica albuginea plications. We conclude that better healing of the onlay flap to spongiosum supported urethral plate may account for the lower fistula rate (6%) observed with the onlay island flap hypospadias repair, and even in severe cases of hypospadias the urethral plate is usually healthy and it does not require division to produce a straight penis.

Primary Dilated Megaureter: Long-Term Followup

Previously, we reported on the changing concepts in the management of 35 neonates with primary obstructive megaureters, 25 of whom were observed without surgery for a mean of 28 months while 10 were surgically treated. We report the long-term outcome of the 25 patients who were managed without surgery. This group consists of 19 male and 6 female neonates with 19 unilateral and 6 bilateral dilated ureters. Of the patients 17 presented with an antenatal diagnosis of hydronephrosis, 2 with infection and 6 with incidental findings. None of the patients had vesicoureteral reflux. Followup serial imaging (2 or more studies per case) consisted of excretory urography in 18 of the 25 cases, diethylenetriaminepentaacetic acid renal scan in 16 and/or sonogram in 10. Mean followup was 7.3 years (range 4.8 to 12.4) for 24 patients and 1 was lost to followup after 1.5 years. Excretory urography showed improvement in urinary tract dilatation in 12 cases and stable dilatation in 6. Renal scans demonstrated expected interval increases in the glomerular filtration rate with age without any deterioration in per cent of renal function in all 16 cases. None of the patients had stones, pain or pyelonephritis. We conclude that it is safe to follow a select group of patients with primary dilated megaureters in the absence of vesicoureteral reflux. We recommend antibiotic prophylaxis and serial urinary tract imaging to confirm renal growth and preservation of renal function.

Nonoperative management of blunt pediatric major renal trauma

Although algorithms exist for the management of renal trauma in adults, guidelines have not been established in children. Of 1,175 patients entered into our Trauma Registry between 1987 and 1991, 61 (5.2%) presented with gross or microscopic hematuria. Eight of the 58 patients (13.8%) who had blunt abdominal trauma had major renal injuries. Gross hematuria (n = 10) was a significant predictor of major renal injury (n = 5) (p < 0.001). All 3 patients with microscopic hematuria and a major renal injury also had evidence of multisystem trauma. Admission blood pressure, hemoglobin, and trauma score were not predictors of major renal trauma. All cases were managed nonoperatively except for 1 patient who required a partial nephrectomy for continued hemorrhage. These data suggest that hematuria of any degree should be evaluated in the pediatric population, since major injuries can occur with even microscopic hematuria or in the absence of shock. Nonoperative management in this series resulted in no morbidity or delayed complications and suggests that surgical exploration be reserved for ongoing bleeding.

Bladder smooth muscle cells in culture. I: Identification and characterization

This report documents the growth and culture characteristics of human and fetal bovine bladder smooth muscle cells in vitro. Bladder smooth muscle cell strains have been identified by their spindle shaped morphology, noncontact inhibited growth characteristics and the expression of smooth muscle cell specific alpha-actin. Extracellular matrix protein biosynthesis by these cells in vitro has been characterized by metabolic labeling of proteins with [14C] radiolabeled proline and analysis by SDS gel electrophoresis. These studies demonstrate that bladder smooth muscle cells synthesize predominantly types I and III collagen, and fibronectin. In addition type III collagen exists in both a partially processed (pN alpha 1[III]) form and processed form. Complementary immunohistochemical studies show localization of type I, III, and IV collagens, and fibronectin to bladder smooth muscle cell extracellular matrix. We conclude that both fetal bovine and human smooth muscle bladder cells are capable of secreting the classic components of the surrounding connective tissue.

Type III collagen decreases in normal fetal bovine bladder development

In normal fetal bovine bladder development we have shown that compliance increases at approximately the same time that urine production first occurs. The late first trimester fetal bladders are relatively stiff with a progressive increase in bladder compliance peaking in the newborn period. From the newborn period through adulthood, we documented a relatively modest decrease in bladder compliance, which may result from the normal aging process. To account for these changes, we have used the bovine model to perform biochemical analyses of the major structural collagens that are found in the bladder (types I and III). These results show that the per cent of type III collagen decreases in the developing bladder from the end of the first trimester until the newborn period. Comparing the newborn bladder to that of a mature adult, we documented a relatively modest increase in the amount of type III collagen. We demonstrated that the ratio of type III-to-type I collagen parallels the normal compliance changes in the developing fetal and mature bovine bladder.

Bovine bladder compliance increases with normal fetal development.

In this study we characterized the elastic properties of the normal bovine bladder throughout fetal life, the newborn period and into adulthood. The elasticity of the bladder was measured with a novel circularly clamped bladder testing system. Pressurization of a circularly clamped bladder tissue sample caused the tissue to deflect upward repetitively in the shape of a spherical cap. If the centerline deflection is much larger than the tissue thickness, the elastic modulus, considered the inverse of compliance, can be determined using linear regression techniques. The results of our analyses showed that the elastic modulus decreases in direct proportion with increasing gestational age. These data suggest that during normal development of the bovine fetal bladder there is a progressive change from a rather stiff noncompliant bladder characterized by a high elastic modulus to a compliant bladder with a lower elastic modulus. Moreover, the increase in compliance appears in the developmental period when urine production first occurs. These observations suggest that volume work may be a significant event in the normal development process of the bovine bladder and results in an increase in bladder compliance. Conversely, the poorly compliant fetal bladder may explain some of the transient dilatations of the upper urinary tract which have been documented in utero. Finally, from the newborn period to the mature adult bovine we documented a relatively modest increase in the elastic modulus or decrease in bladder compliance which may reflect the normal aging process.

Genitoplasty for intersex anomalies

The child born with ambiguous genitalia requires prompt diagnosis, sex assignment and treatment. The incidence of intersex is approximately 1 in 30,000 newborns [7]. These patients are categorized based on the their gonadal presentation into female pseudo-hermaphrodites, male pseudohermaphrodites, true hermaphrodites and mixed gonadal dysgenesis [2, 6] (Table 1). The majority of these cases (60-70%) will be female pseudohermaphrodites secondary to the adrenogenital syndrome (types I-IV) (Table 2). Simply put, these patients suffer from a block in the normal production of cortisone which by negative feedback from the pituitary results in the continued stimulation and overproduction of the by products of steroid metabolism in the adrenal gland. High levels of androgenic steroids leads to various degrees of masculinization in the XX fetus with exclusively ovarian tissue for gonads. Variable degrees of phallic enlargement, fusion of the urethral folds to form a phallic urethra and proximal entry of the vagina into the urogenital sinus are the resulting effects. These babies may look like males with bilateral cryptorchidism and hypospadias. Secondary to an increase in ACTH production, these patients may also have hyperpigmentation of their skin over the external genitalia and nipples. Rarely, abnormal androgen stimulation in the fetus may come from the mother either from exogenous ingestion of androgen hormones or from maternal androgen secreting tumors [2, 6]. Excessive aldosterone production leads to salt wasting which is life threatening if not recognized and treated. Male pseudohermaphrodites encompass a wide group of patients with varying etiologies that may present as intersex patients in the newborn period or during hormonal changes associated with puberty. Together these patients all have exclusively testicular tissue with a 46,XY karyotype. The pathology in this group results from the inability of the testis to synthesis testosterone or the failure of target tissues to respond to circulating testosterone (androgen insensitivity). The decision to raise the child as a male centers around the potential for the phallus to function adequately in later sexual relations. Presently, attempts at phallic reconstruction have been disappointing [34, 35]. Because of this, in questionable cases, the tendency has been to choose a female sexual identity.

Effect of mechanical forces on extracellular matrix synthesis by bovine urethral fibroblasts in vitro.

The role of mechanical forces in normal physiological processes is just beginning to be elucidated. Using a system developed in our laboratory, we can apply precise and reproducible mechanical deformations (biaxial strain) to cells. These deformations alter cell activities in a reproducible fashion and may mimic the physical environment found in portions of the urinary tract. At a low strain of 1.8% no change in the synthesis of types I and III collagen by urethral fibroblasts was found. However, at a high strain (4.9%) types I and III collagen showed a significant increase in synthesis compared to controls (type I, 1.4 +/- 0.25 microgram. versus 0.9 +/- 0.27 microgram., p = 0.053; type III, 110 +/- 7 ng. versus 88 +/- 10 ng., p = 0.036). In addition, fibronectin synthesis was increased at low and high strains when compared to controls (low strain 3.20 +/- 1.03 micrograms. versus 1.46 +/- 0.15 microgram., p = 0.042; high strain 8.90 +/- 1.09 micrograms. versus 3.12 +/- 0.69 microgram., p = 0.001). We have shown at the cellular level that mechanical force applied to fetal bovine urethral fibroblasts results in an increase in the amount of collagen synthesis and fibronectin synthesis. These findings suggest that alterations in the physical environment of cells found in the urethral wall can affect biochemical processes including those that govern the synthesis of structural macromolecules such as collagen.

Congenital penile curvature (chordee without hypospadias)

We treated 30 patients aged six months to nine years with congenital penile curvature from 1988 to 1993. Twenty-four patients appeared to have a primary curvature with normal corpus spongiosum. In 12 of these 24 patients dissecting skin and dartos fascia were adequate to straighten the penis. In the other 12 patients, artificial erection demonstrated a varied degree of convexity of the penis after the skin and dartos fascia release, implying a disproportion of the corpora cavernosa bodies. We corrected this deformity using dorsal tumica albuginea plications (TAP). The remaining 6 patients presented with a primary curvature and hypoplastic urethra. In 5 of these patients we divided the hypoplastic midportion of the urethra leaving the meatus naturally on the glans and replaced the midurethral segment using a tubularized island flap. Of these 5 patients 2 required TAP for penile straightening. The final patient with a hypoplastic urethra was managed by preserving the urethral plate and applying an only island flap urethroplasty. Complications were one fistula and two mild ventral penile curvatures, presently not severe enough for reoperation (mean follow-up 2.6 years). We present a systematic approach for the repair of congenital penile curvature using intraoperative artificial erection, TAP, and the island flap urethroplasty when needed.

Culture of Urethral Fibroblasts: Cell Morphology, Proliferation and Extracellular Matrix Synthesis

The in vitro morphology and proliferative activity of urethral fibroblasts were characterized from primary isolates of fetal bovine urethral spongiosum. Cells were identified as fibroblastic based on their spindle-shaped morphology and lack of expression of phenotypic markers characteristic of either urethral smooth muscle or epithelial cells. Urethral fibroblasts proliferated at a steady rate and did not exhibit contact-inhibition of growth in a culture medium of Medium 199 supplemented with 10% newborn calf serum. Both immunohistochemistry and metabolic labeling analyses of extracellular matrix synthesis demonstrated the presence of collagen types I and III, and fibronectin. Quantitation of the collagenous components of the cell medium revealed that urethral fibroblasts synthesize 85% type I collagen, 14% type III collagen and < 1% type V collagen. In contrast, the urethral fibroblast cell layer matrix consisted of 98% type I collagen, < 1% type III and < 1% type V collagen.