Leydig cell tumors and tumors associated with congenital adrenal hyperplasia.

Testicular cancers occur at a rate of 2 cases per 100,000 males. Gonadal stromal tumors, including Leydig cell tumors and tumors of the adrenogenital syndrome, account for 1% to 3% of these neoplasms. Despite their rarity, these hormone-producing tumors are particularly interesting because of their potential for causing endocrinologic manifestations in prepubertal and adult males. They are also clinically significant, and early identification is critical to avoid profound and often irreversible developmental changes in affected children. An accurate diagnosis is important to differentiate tumors that will respond to medical management from tumors that require definitive surgical therapy.

Repair of hypospadias complications using the previously utilized urethral plate.

OBJECTIVES: To review our results of patients who underwent repeat hypospadias surgery using local skin flaps with preservation of the urethral plate. METHODS: We retrospectively reviewed the medical records of all patients who underwent a reoperative hypospadias repair using the urethral plate between 1988 and 1996. A total of 53 patients were identified who developed either a large fistula (47 patients) or severe stricture (6 patients) after the initial repair. Seventeen patients underwent a repeat Mathieu flip-flap and 36 an onlay flap. The mean age at the time of surgery was 5.2 years (range 1 to 27). The mean duration of follow-up was 17 months (range 6 to 108). RESULTS: The initial failed hypospadias repair was corrected with a single procedure in 44 (83%) of the 53 patients. The 9 patients who had further complications required 17 additional procedures. A meatal-based flap had been used in 4 of these patients and an onlay flap in 5. Three of the 9 patients who had further complications presented with urethral strictures after the previous repair. CONCLUSIONS: Fistula and stricture are common complications of hypospadias surgery. The use of the urethral plate in primary repairs has helped decrease the complication rate. We report the effectiveness of using local skin flaps and preserving the urethral plate in complex reoperative hypospadias surgery. These techniques were successful in 83% of these challenging patients. Patients with stricture after hypospadias surgery are at increased risk of further complications.

Tumors of the adrenogenital syndrome: an aggressive conservative approach.

PURPOSE: Testicular masses in male individuals with the adrenogenital syndrome are a clinical and pathological diagnostic dilemma. The major differential diagnosis of gonadal nodules in this setting includes interstitial Leydig cell tumors and secondary benign tumors of possible adrenal rest origin. Management of these 2 entities obviously differs. We report clinical, biochemical and pathological features in 3 children with rare bilateral testicular masses and the adrenogenital syndrome in an attempt to define better the natural history of these entities and formulate recommendations for management. MATERIALS AND METHODS: All 3 patients had a history of precocious puberty. Two boys were diagnosed with the adrenogenital syndrome at birth, and presented with bilateral testicular masses at ages 5 and 17 years, respectively. The remaining patient was diagnosed at age 15 years after testicular and adrenal masses developed. All 3 cases were classified as 21-hydroxylase deficiency with markedly elevated levels of 17-hydroxyprogesterone, dehydroepiandrosterone, adrenocorticotropic hormone and androstenedione. Testosterone levels were mildly elevated above normal age matched values. Testicular biopsies were done in each case. RESULTS: Two cases were initially interpreted as bilateral Leydig cell tumors but they were histologically reclassified as tumors of the adrenogenital syndrome. The other case was diagnosed as interstitial cell hyperplasia. Although corticosteroid therapy corrected each steroid abnormality, in no case did tumors resolve, but there was gradual regression in 1. Each patient has been followed conservatively for 4 years. There has been no increase in tumor size or evidence of metastatic disease. CONCLUSIONS: Bilateral testicular masses in children with the adrenogenital syndrome may mimic Leydig cell tumors, which also commonly cause precocious puberty. Orchiectomy for Leydig cell tumors in boys with precocious puberty is contraindicated without a complete endocrinological profile. When congenital adrenal hyperplasia is diagnosed, these tumors appear to be derived from cells of possible adrenal origin stimulated by adrenocorticotropic hormone and they may be followed conservatively.

Natural history of refluxing distal ureteral stumps after nephrectomy and partial ureterectomy for vesicoureteral reflux.

PURPOSE: We evaluated the natural history of refluxing distal ureteral stumps after nephrectomy and partial ureterectomy. MATERIALS AND METHODS: Between 1985 to 1996, 38 patients a mean age of 37 months underwent nephrectomy and partial ureterectomy for reflux into a nonfunctioning kidney. The diagnosis included primary reflux in 23 patients, reflux associated with posterior urethral valves in 10 and ipsilateral ureterocele in 5. Mean followup was 45 months. RESULTS: Only 1 patient with an ipsilateral ureterocele and 1 with contralateral reflux (5%) had symptomatic infections during postoperative followup, and each underwent a secondary procedure to remove the ureteral stump. No patient with only primary unilateral reflux required surgery for the refluxing stump. CONCLUSIONS: Because of the low risk of morbidity associated with a refluxing ureteral stump, we recommend nephrectomy and proximal ureterectomy in patients with reflux into a nonfunctioning kidney.

Bladder calculi in the pediatric augmented bladder.

PURPOSE: Bladder augmentation is now a commonly accepted treatment in children with neuropathic bladder and other bladder anomalies. Bladder calculi have been reported in a third to a half of pediatric patients after bladder augmentation. We identify the incidence of bladder calculi and risk factors for stone formation in a large series of pediatric patients after bladder augmentation. MATERIALS AND METHODS: We reviewed the records of 286 patients who underwent bladder augmentation between 1978 and 1994, assessed the incidence of and risk factors for bladder calculi, and reviewed treatment methods. RESULTS: Bladder calculi developed in 29 of the 286 patients (10%) who underwent bladder augmentation. The type of bowel used for augmentation did not affect the rate of stone formation except stomach, which did not lead to stone formation in any case. Stones formed more commonly after bladder outlet resistance procedures and in patients with catheterizable abdominal wall stomas. Patients underwent open cystolithotomy or cystolitholapaxy with an overall 44% recurrence rate and no statistically significant difference between treatment methods. CONCLUSIONS: Bladder calculi are a known complication of bladder augmentation. An increased risk of stone formation is associated with bladder outlet resistance procedures and catheterizable abdominal wall stomas. Daily irrigations to clear mucus and crystals as well as complete emptying of the augmented bladder may have important roles in decreasing stone formation.

Etiology, management and surgical complications of congenital chordee without hypospadias.

PURPOSE: We comprehensively evaluated the etiology, management and surgical complications of chordee without hypospadias. MATERIALS AND METHODS: We reviewed the records of patients who underwent chordee correction between January 1985 and December 1996. A total of 87 patients with a median age of 14 months were treated for chordee without hypospadias. Mean followup was 10 months. Patients were treated in the standard fashion and a straight phallus was confirmed in all postoperatively. We grouped cases according to the etiology of chordee, including skin tethering, fibrotic dartos and Buck's fasciae, corporeal disproportion and urethral tethering. RESULTS: Of the 87 patients 28 (32%) were successfully treated with release of the skin and superficial fascia. In 29 cases (33%) extensive resection of the fibrotic dartos and Buck's fasciae was necessary to straighten the phallus, including 2 (7%) in which chordee recurred. Corporeal disproportion was identified in 24 patients (28%), of whom 2 (8%) also had complications (urethrocutaneous fistula and recurrent chordee in 1 each). In 6 cases (7%) urethral tethering was the etiology of chordee, of which 3 (50%) had complications (urethrocutaneous fistula and recurrent chordee in 2 and 1, respectively). Overall 80 of the 87 patients (92%) were successfully treated with 1 operation. CONCLUSIONS: In our series the etiology of chordee without hypospadias was evenly divided among skin tethering, fibrotic dartos and Buck's fasciae, and corporeal disproportion. A congenitally short urethra was a rare cause of isolated chordee. Surgical correction is highly successful with a low 8% complication rate.

Augmenting the augmented bladder: treatment of the contractile bowel segment.

PURPOSE: Bowel used for bladder reconstruction regardless of detubularization occasionally retains its contractile properties. Of 323 patients who underwent primary enterocystoplasty we identified 19 who continue to have high pressure bladder contractions and required augmentation of the previously augmented bladder. MATERIALS AND METHODS: Reason for repeat augmentation, upper tract changes, original and secondary bowel segments used, and urodynamic findings were evaluated in all patients. Current status and followup also were noted. RESULTS: After initial augmentation 8 patients had persistent incontinence, 5 bladder perforation, 3 isolated upper tract changes, 2 incontinence and bladder perforation, and 1 incontinence plus intractable pain. Preoperative urodynamics revealed detrusor pressures from 30 to 100 cm. water. All patients had adequate bladder outlet resistance. The original bowel segments used were sigmoid in 12 cases, stomach in 4, ileum in 2 and cecum in 1. Bowel segments for re-augmentation were ileum in 16 cases and sigmoid in 3. Of the 11 patients with incontinence 10 are now dry. All cases of upper tract changes resolved. Mean followup since re-augmentation is 52 months. CONCLUSIONS: If the outcome of bladder augmentation is less than optimal, it is important to reevaluate the bladder dynamics. In rare instances these patients may continue to have high pressure contractions with a functionally small bladder capacity. In such situations reaugmentation with an additional bowel segment is an excellent alternative to a difficult clinical problem and provides good results in the vast majority of cases. This treatment may not totally alleviate the contractions but it does decrease them and increase the volumes at which the contractions occur, making them no longer clinically or functionally significant.

Rabbit urethral regeneration using small intestinal submucosa onlay grafts.

OBJECTIVES: To determine if small intestinal submucosa (SIS) can evoke urethral regeneration. METHODS: Twenty male white New Zealand rabbits were assigned to one of three experimental groups. Group 1 (n = 4) underwent simple urethrotomy and closure. Group 2 (n = 8), a second control group, underwent an onlay urethroplasty with a graft of full-thickness preputial skin from the host rabbit. Group 3 (n = 8) underwent an onlay urethroplasty with an SIS graft. RESULTS: All eight SIS onlay grafts promoted regeneration of the normal rabbit epithelium supported by a well-vascularized collagen and smooth muscle backing. Preputial free onlay grafts maintained a keratinizing squamous cell epithelium with a poor supportive backing, which resulted in the formation of urethral diverticulum. CONCLUSIONS: SIS onlay patch grafts for urethroplasty promote rabbit urethral regeneration.

Management of ectopic ureters: experience with the upper tract approach.

PURPOSE: The necessity of removing the ureteral stump after upper tract surgery for an ectopic ureter has been debated. We reviewed the records of patients initially treated at the kidney level to evaluate indications for later stump removal. MATERIALS AND METHODS: We reviewed the medical records of 32 patients with 33 ectopic ureters treated at the kidney level during the last 10 years. RESULTS: Ectopic ureters were associated with duplicated collecting systems in 31 cases and with single systems in 2. Upper pole heminephrectomy and partial ureterectomy were performed in 23 units and upper tract reconstruction was done in 8. Both patients with single systems underwent nephrectomy. Four patients (12%) required repeat surgery at the bladder level, including 1 who underwent ureteral reimplantation for persistent ipsilateral lower pole reflux and simultaneous upper pole stump removal. Preoperative voiding cystourethrography revealed reflux into the ectopic ureter in 1 patient with postoperative reflux and infections. The remaining 2 patients required a repeat operation to remove the stump due to recurrent urinary tract infections and newly detected reflux into the stump, respectively. CONCLUSIONS: The majority of patients with ectopic ureters can be treated by addressing only the upper urinary tract. No patient who presented with incontinence required ureteral stump removal. Whether noted preoperatively or postoperatively, reflux into the ectopic ureter necessitated ureteral stump removal. Three of the 6 patients (50%) who had reflux to the ipsilateral kidney required lower tract surgery.

Reconstruction of the high urogenital sinus: early perineal prone approach without division of the rectum.

PURPOSE: Reconstruction of the vagina and external genitalia in the infant is quite challenging, particularly when a urogenital sinus is associated with high confluence of the vagina and urethra. Many surgeons believe that children with such a malformation should undergo staged or delayed reconstruction, so that vaginoplasty is done when the child is older and larger. Vaginoplasty early in life is thought to be difficult due to patient size and poor visualization. The posterior sagittal approach has been beneficial for acquiring exposure to high urogenital sinus anomalies but it has been thought to require splitting of the rectum and temporary colostomy. We report a modification of this technique. MATERIALS AND METHODS: In the last 5 years all patients with urogenital sinus anomalies underwent reconstruction using a single stage approach regardless of the level of confluence. In 8 patients with a high level of confluence reconstruction was performed using a perineal prone approach. Exposure was achieved without division of the rectum. The operative technique is presented in detail. RESULTS: This midline perineal prone approach has allowed excellent exposure of the high vagina even in infants. In all 8 patients reconstruction was done without difficulty and no patient required incision of the rectum or colostomy. This procedure did not preclude the use of a posteriorly based flap for vaginal reconstruction. CONCLUSIONS: While patients with low confluence can be treated with single posteriorly based flap vaginoplasty, those with higher confluence may benefit from a perineal prone approach to achieve adequate exposure for pull-through vaginoplasty. This prone approach to the high urogenital sinus anomaly can be performed without division of the rectum, provides excellent exposure of the high confluence even in small children and does not preclude the use of posterior flaps for vaginal reconstruction.

Upsizing of the artificial urinary sphincter cuff to facilitate spontaneous voiding.

OBJECTIVES: Following placement of an artificial urinary sphincter (AUS) in the male child, functional and mechanical alterations can ensue, resulting in an inability to void spontaneously. One possible mechanical etiology in the patient entering puberty is prostatic growth within the fixed mechanical confines of the AUS cuff, resulting in progressive bladder outlet obstruction. Unrecognized infravesical obstruction can, in turn, lead to upper urinary tract deterioration, sepsis, or renal failure. We evaluated the effect of somatic growth and maturation of the male urethra on voiding dynamics in boys with an AUS to specifically determine whether revision of the sphincter cuff (ie, upsizing) is beneficial in restoring the ability to void spontaneously. METHODS: A retrospective review of 124 children with an AUS was performed. Eleven boys were identified whose bladder neck cuffs were later upsized in an attempt to improve bladder emptying. All boys were prepubertal at the time of original cuff placement. The average interval between the initial operation and cuff upsizing was 5 years. RESULTS: Following original sphincter placement, 8 patients emptied to completion spontaneously and 3 patients emptied by intermittent catheterization. All eight of the spontaneous voiders experienced progressive difficulty emptying after they entered puberty and ultimately had to rely on clean intermittent catheterization to empty completely. Follow-up subsequent to cuff exchange averaged more than 5 years (range 1 to 10 years). Despite an average increase of 10 mm in cuff size, all patients continued to depend on intermittent catheterization to empty completely. CONCLUSIONS: Upsizing the bladder cuff in the maturing male who experiences difficulty with bladder emptying does not restore the ability to void spontaneously.

Principles in management of complex pediatric genitourinary plexiform neurofibroma.

Neurofibromatosis is a hamartomatous disorder of neural crest derivation characterized by cutaneous pigmentation and tumor formation in various tissues. Visceral involvement is typically insidious, progressive, and difficult to treat. Plexiform neurofibroma of the urinary tract is rare. Involvement of nearly every genitourinary structure by these lesions has been reported, with the bladder being most commonly involved. In part due to the small number of patients seen at any one institution and the highly variable location and extent of this disease process, a plan for management of individuals with genitourinary neurofibromatosis has not been proposed. In an attempt to define specific goals in treatment of such patients, we reviewed our population of 260 pediatric patients with type 1 neurofibromatosis. We present our series of 5 patients with complex genitourinary lesions and describe specific management principles.

PCR and FISH analysis of a ring Y chromosome.

A newborn male infant presented with midshaft hypospadias, chordee, and undescended left testis. Both gonads lacked the tunica albuginea and appeared to be adjacent to structures resembling fallopian tubes. On biopsy, there was marked dysgenesis of both gonads, with a paucity of testicular tubules and foci of ovarian-like stroma. Peripheral blood karyotype was 46,X,mar(Y) [39]/45,X [5]. Right gonadal biopsy material showed the same mosaicism but with a higher proportion of 45,X cells (46%). PCR and FISH analyses with primers/probes from different Yp, Yq, and Ycen loci defined the structure of the marker Y as a probable complex ring with breakpoints in Yq11.21 (very close to the centromere) and in Yp11.32 (the pseudoautosomal region). Based on the phenotype and the laboratory findings, the prognosis given to the patient was for short stature and azoospermia without an increased risk for gonadoblastomas.

Characterization of small intestinal submucosa regenerated canine detrusor: assessment of reinnervation, in vitro compliance and contractility.

PURPOSE: We characterized small intestinal submucosa regenerated canine bladder. MATERIALS AND METHODS: We subjected 15-month small intestinal submucosa regenerated canine bladder strips to in vitro muscle bath compliance, contractility testing and immunohistochemical staining. RESULTS: Compliance studies demonstrated no significant difference between small intestinal submucosa regenerated and control bladders, which were 30-fold more compliant than native small intestinal submucosal graft material. Contractility studies demonstrated contractile responses and innervation similar to those of normal canine bladder. Afferent nerves were demonstrated through immunohistochemical techniques. CONCLUSIONS: These characteristics further support the regenerative capacity of small intestinal submucosa and its potential use as a bladder augmentation material.

Penile orthoplasty using dermal grafts in the outpatient setting.

OBJECTIVES: To review and evaluate our extensive outpatient experience in the use of dermal grafts for the correction of significant residual chordee in patients requiring penile orthoplasty. METHODS: The medical records of all patients requiring surgical correction for severe penile curvature over the past 5 years were reviewed. Among these, 51 patients were identified in whom dermal grafts were used to correct severe residual chordee. Of these patients, 41 had severe hypospadias, 9 had epispadias, and 1 had urethral atresia. Graft harvest and placement technique, any resulting complications, and parental satisfaction with cosmetic and functional results were all evaluated. RESULTS: The dermal grafts were harvested from the hairless skin of the inguinal area, using one of two techniques. All were used to fill a tunical defect created by incising the tunica at the point of maximal penile curvature. No complications or postoperative hospitalizations resulted from any of the orthoplasty procedures. At a mean follow-up of 27 months, all patients had excellent cosmetic and functional results. CONCLUSIONS: In patients with significant residual chordee, a dermal graft is our preferred method of penile orthoplasty. This technique provides a straight phallus with a very minimal complication rate, it can easily and successfully be performed as an outpatient procedure, and it has assured an excellent cosmetic and functional result.

Regenerative urinary bladder augmentation using small intestinal submucosa: urodynamic and histopathologic assessment in long-term canine bladder augmentations.

PURPOSE: To evaluate small intestinal submucosa (SIS) as a possible bladder augmentation material. MATERIALS AND METHODS: Nineteen male dogs underwent 35 to 45% partial cystectomy with immediate augmentation with SIS grafts. All dogs were evaluated pre- and postoperatively with blood chemistries, urine cultures, intravenous urograms, cystograms and cystometrograms. Postoperatively (1 to 15 months), bladders were examined with routine histology and image analysis. RESULTS: All dogs survived their intended survival period without morbidity. All results were normal. Histologically, all 3 layers (mucosa, smooth muscle, serosa) of the normal bladder showed evidence of regeneration. CONCLUSIONS: Small intestinal submucosa acts as a scaffold for bladder augmentation through regeneration and could be a potential option for bladder reconstruction.

Enterocystoplasty: the star modification.

PURPOSE: A modification of sagittal cystoplasty is described that maximally reconfigures the native neuropathic bladder, as required in enterocystoplasty. MATERIALS AND METHODS: The star modification incorporates lateral cystotomies with anteroposterior cystotomy, as in the widely used sagittal clamshell technique. RESULTS: Enterocystoplasty was performed in 27 patients with various bowel segments using this technique and none has had complications attributable to cystoplasty after a mean followup of 2.5 years. CONCLUSIONS: Star reconfiguration defunctionalizes any potential noncompliant or hyperreflexic tendencies inherent to the neuropathic bladder before augmentation. In addition, the modification provides a technical advantage by increasing the linear length of the edge available for the anastomosis of bowel to bladder.

New chemotherapeutic agents in acute myeloid leukemia.

Only two classes of chemotherapeutic agents have shown activity in acute myeloid leukemia (AML): ara-C and topoisomerase II reactive agents. Frontline combinations of these agents produce complete response (CR) rates of 70% and long-term event free survival rates of 25%. New agents with different mechanisms of action are being explored. Nucleoside analogs such as chlorodeoxyadenosine (2-CdA) or fludarabine have shown single-agent efficacy and may be synergistic with ara-C. Combination therapy with ara-C and nucleoside analogs have shown promising results both as salvage therapy and in newly diagnosed patients. Combinations of topotecan with ara-C, VP16, and anthracyclines are being pursued, as is testing of other Topo-I inhibitors. Hypomethylating agents (5-azacytidine, decitabine) are showing activity in AML, producing CR rates of 5% to 30% as AML salvage therapy as a single agent, and 40%-60% in combinations. Decitabine may be synergistic with topo I inhibitors, biologic agents, and differentiating agents. Homoharringtonine has modest anti-AML activity, with CR rates of 10% to 30% as salvage therapy. Other classes of agents worthy of continuing investigation are platinum analogs and agents with novel mechanisms of action such as tallimustine.

Femoral nerve neuropathy after the psoas hitch procedure.

We report the first 3 cases of femoral nerve neuropathy after a psoas hitch vesicopexy, a technique commonly used with ureteroneocystostomy. The condition in 2 patients resolved with conservative therapy, and the third patient required reoperation with removal of an offending suture. All 3 patients recovered completely with no residual neurologic deficit. Urologists who use the psoas hitch must be familiar with this potential complication to prevent its occurrence.