Surgery in disorders of sex development (DSD) with a gender issue: If (why), when, and how?

Ten years after the consensus meeting on disorders of sex development (DSD), genital surgery continues to raise questions and criticisms concerning its indications, its technical aspects, timing and evaluation. This standpoint details each distinct situation and its possible management in 5 main groups of DSD patients with atypical genitalia: the 46,XX DSD group (congenital adrenal hyperplasia); the heterogeneous 46,XY DSD group (gonadal dysgenesis, disorders of steroidogenesis, target tissues impairments …); gonosomic mosaicisms (45,X/46,XY patients); ovo-testicular DSD; and "non-hormonal/non chromosomal" DSD. Questions are summarized for each DSD group with the support of literature and the feed-back of several world experts. Given the complexity and heterogeneity of presentation there is no consensus regarding the indications, the timing, the procedure nor the evaluation of outcome of DSD surgery. There are, however, some issues on which most experts would agree: 1) The need for identifying centres of expertise with a multidisciplinary approach; 2) A conservative management of the gonads in complete androgen insensitivity syndrome at least until puberty although some studies expressed concerns about the heightened tumour risk in this group; 3) To avoid vaginal dilatation in children after surgical reconstruction; 4) To keep asymptomatic mullerian remnants during childhood; 5) To remove confirmed streak gonads when Y material is present; 6) It is likely that 46,XY cloacal exstrophy, aphallia and severe micropenis would do best raised as male although this is based on limited outcome data. There is general acknowledgement among experts that timing, the choice of the individual and irreversibility of surgical procedures are sources of concerns. There is, however, little evidence provided regarding the impact of non-treated DSD during childhood for the individual development, the parents, society and the risk of stigmatization. The low level of evidence should lead to design collaborative prospective studies involving all parties and using consensual protocols of evaluation.

Germ cell tumor in an adolescent with extensive testicular microlithiasis: concerns regarding future management.

We report on a 14-year-old boy with bilateral testicular microlithiasis and a right-sided testicular tumor. Tumor markers alpha-fetoprotein (AFP) and ß-human chorionic gonadrotropin (ß-hCG) levels were elevated and orchiectomy revealed a mixed germ cell tumor consisting of embryonal carcinoma, yolk sac tumor, choriocarcinoma, and mature teratoma. The patient had no evidence of metastatic disease. Although there is a strong association between testicular microlithiasis and testicular tumor, the pediatric literature is varying in the recommended surveillance of these patients. The literature and management of pediatric patients with testicular microlithiasis is herein reviewed.

Colovaginoplasty using the Yang-Monti modification.

OBJECTIVE: Bowel vaginoplasty is particularly difficult in patients who are extremely obese or those with an android pelvis. This report evaluates the use of the Yang-Monti principle as a viable alternative in the reconstruction of these patients. METHODS: Upon retrospective chart review of patients who underwent bowel replacement vaginoplasty between 1980 and 2008, 4/60 were identified who underwent the Yang-Monti modification. The neovagina was created with an 8‒10-cm segment of descending colon which was detubularized and then retubularized using the Yang-Monti principle. This was sewn in place in the perineum. Outcome was evaluated by physical examination data and clinical information on postoperative sexual function. RESULTS: Three of the four patients had an XY karyotype and an android pelvis, and of these two were failures of previous ileovaginoplasties and one was a failed colovaginoplasty. The fourth was a case of primary mullerian failure (XX) in a morbidly obese individual. All four were discharged without complication following surgery. With a median follow-up of 6 years (range 4-9), none showed evidence of introital stenosis or required dilation. Two were engaged in vaginal intercourse at last consultation, and they reported vaginal length was adequate. No further procedures were required in any of the patients at the end of the follow-up period. CONCLUSION: The Yang-Monti modification, when used as an adjunct to colovaginoplasty, can be an effective reconstructive technique in this subset of patients. It allows for lengthening of the neovagina, without perpetuating tension on the vascular pedicle.

Endoscopic management of vesicoureteral reflux in adult women.

OBJECTIVE: • To describe our endoscopic management of adult women with vesicoureteral reflux (VUR) and associated outcomes. PATIENTS AND METHODS: • We retrospectively identified 19 adult women who presented for the endoscopic treatment of VUR from November 2001 to January 2008. • Each patient was diagnosed with VUR by voiding cystourethrogram or nuclear cystourethrogram after an episode of pyelonephritis or recurrent urinary tract infections with renal scarring on ultrasound. • A dimercaptosuccinic acid renal scan was performed prior to treatment. All patients underwent endoscopic treatment with dextranomer/hyaluronic acid copolymer (Deflux). Patients with bilateral VUR received bilateral injections during the same procedure. • Follow-up imaging was obtained and success was strictly defined as no degree of VUR. Patients with residual VUR received repeat endoscopic treatment. RESULTS: • Nineteen patients with a mean age of 22 years old (range 18-33 years old) underwent endoscopic treatment for VUR. A total of 79% (15/19) had pre-existing risk factors for VUR, including prior open anti-reflux surgery (26%), family history of VUR (26%) and childhood diagnosis of VUR (26%). • Imaging revealed that 47% (9/19) had renal scarring and 26% (5/19) had bilateral VUR. The success rate was 79% (19/24) after one treatment, 92% (22/24) after 5 patients received a second treatment, and 96% (23/24) after 2 patients received a third treatment. There were no perioperative complications. CONCLUSION: • Endoscopic management of VUR is both safe and effective in adult women.

Overnight urethral stenting after tubularized incised plate urethroplasty for distal hypospadias.

OBJECTIVES: The duration of urethral stenting after tubularized incised plate (TIP) urethroplasty for hypospadias varies among surgeons. Typically the catheter is left for up to 7 days with the goal of minimizing post-operative complications. We describe our experience with overnight stenting for distal TIP hypospadias repair. MATERIALS AND METHODS: A retrospective chart review was performed on patients who underwent TIP hypospadias repair from 2003 to 2008. Patients who had their urethral catheter overnight were included in this analysis. Outcomes analyzed were the rates of: urethrocutaneous fistula, meatal stenosis, urethral stricture and urinary tract infections. RESULTS: A total of 64 patients underwent outpatient TIP hypospadias repair. Forty-nine patients had overnight urethral stenting with at least 12 months follow-up and were included in the analysis. Five of the 49 patients (10.2%) developed urethrocutaneous fistula. Of these five patients, two had undergone re-do hypospadias repair. The fistula rate in primary repairs was 3/45 (6.7%). There were no incidences of meatal stenosis, urinary tract infections or urethral strictures. CONCLUSION: In our experience, overnight urethral stenting for TIP hypospadias repair does not significantly affect the rates of urethrocutaneous fistula, meatal stenosis and urinary tract infections. Patients who have had a primary TIP hypospadias repair may have their urethral catheter removed safely on post-operative day one.

Hypospadias rates in new york state are not increasing.

PURPOSE: The testicular dysgenesis syndrome describes urogenital abnormalities associated with exposure to environmental endocrine disruptors such as phthalates, specifically decreased semen quality, and increased rates of testis cancer and hypospadias. Recently there has been concern that these abnormalities described in animal studies may also be present in humans. To determine if hypospadias rates are increasing, we retrospectively reviewed the total prevalence of hypospadias in New York State from 1992 to 2005, categorized by maternal age younger than 35 years and 35 years or older. MATERIALS AND METHODS: Hypospadias rates were obtained from the New York State Congenital Malformations Registry from 1992 to 2005. An analysis was also performed on the rates of children with hypospadias who had mothers younger than 35 years and mothers 35 years or older. This investigation was approved by the Columbia University internal review board. RESULTS: There was no statistical change in hypospadias rates in New York State from 1992 to 2005 (r = 0.127, p = 0.6). Overall the mean +/- SE prevalence rate was 34.9 +/- 0.36 per 10,000 live births. However, mean +/- SE hypospadias rates in children of mothers 35 years old or older (38.7 +/- 0.7) were significantly greater than those in children of mothers younger than 35 years (34.1 +/- 0.386, t test p <0.01). CONCLUSIONS: Hypospadias rates have not changed in New York State from 1992 to 2005. Additionally advanced maternal age continues to be a risk factor for hypospadias. Combined with previous studies that demonstrate sperm counts are not declining, these data suggest that the testicular dysgenesis syndrome described in animal models may not be evident in humans.

Part 2: Examining pediatric vesicoureteral reflux: a real-world evaluation of treatment patterns and outcomes.

OBJECTIVE: Vesicoureteral reflux (VUR) occurs in 1% of infants and children. Upon diagnosis, patients are often placed on prophylactic antibiotics to prevent urinary tract infections (UTIs) and potential renal damage. The objective of this study was to assess current diagnosis and treatment patterns for patients diagnosed with VUR, focusing on compliance with antibiotic therapy and the occurrence of UTIs. METHODS: This is a retrospective study of children less than 11 years of age diagnosed with VUR. Data were obtained from a national managed care database with over 45 million lives. Patients were followed for up to 6 months prior to their diagnosis and 1 year after. All were required to be eligible for medical and pharmacy services for 1 year after diagnosis. Outcome measures included the use of and compliance with prophylactic antibiotics, rates of curative treatment (surgery and endoscopic injections), and diagnoses of UTIs. RESULTS: There were 35 450 patients meeting inclusion criteria. After being diagnosed with VUR, 76.5% of patients were placed on prophylactic antibiotics, 1.5% had open surgery, and 0.38% had an endoscopic injection with dextranomer/hyaluronic acid copolymer (Dx/HA). Only 17% of patients on prophylactic antibiotics were adherent to therapy, with mean patient compliance equaling 41.4%. Of patients on prophylactic antibiotic therapy, 58% still had a diagnosis for a UTI within 12 months of VUR diagnosis. LIMITATIONS: Adherence to VUR-related antibiotic therapy may be overestimated as the data used in the analysis represents prescriptions acquired but not necessarily consumed. This study lacked detailed clinical information, such as VUR-resolution rates and VUR grade. CONCLUSIONS: Only 17% of pediatric VUR patients on prophylactic antibiotics were compliant with therapy. Of patients on prophylactic therapy, 58% had a diagnosis of a UTI within 1 year of treatment.

A review of metabolic consequences and long-term complications of enterocystoplasty in children.

This review summarizes the important metabolic consequences and long-term complications associated with enterocystoplasty, with a particular emphasis on the pediatric patient with genitourinary abnormalities. A directed Medline literature review for metabolic and long-term complications following enterocystoplasty was performed. Information gained through published literature and from our database was reviewed and summarized to provide the reader with a thorough review of the subject. Bowel is not a perfect tissue for substitution or augmentation, and its use to treat functionally and structurally compromised bladders is associated with several metabolic consequences and long-term complications. Metabolic acidosis is the most common metabolic abnormality seen. The rates and severity of these complications vary, though they may have a profound impact on a patient's quality of life after enterocystoplasty. The metabolic consequences and long-term complications associated with enterocystoplasty are important clinical features of this intervention, and careful consideration should be given to them before pursuing enterocystoplasty.

A review of failures of endoscopic treatment of vesicoureteral reflux with dextranomer microspheres.

PURPOSE: We evaluated the appearance of the mound of failed endoscopic dextranomer microsphere injections at the time of reinjection or open ureteral reimplantation. MATERIALS AND METHODS: We performed a multi-institutional study of 80 patients (97 ureters) who were diagnosed with vesicoureteral reflux and had failed endoscopic treatment with dextranomer microspheres. Observations of injected mound characteristics were made during the time of reinjection or at open ureteral reimplantation. Correlations were made with the pre-injection grade of reflux, volume of initial injection, number of punctures used for the initial injection and presence of symptoms of dysfunctional voiding. RESULTS: Examination of the failed injection sites before subsequent injections or open surgery revealed mound abnormalities in all but 13 of the 97 ureters. Of the cases 49% demonstrated a shifted mound, 22% an absent mound and 10% a loss of volume in the mound. Of the 13 patients with normal appearing mounds 7 had improved reflux grade, 3 had worsened grade and 3 had no change. Patients with dysfunctional voiding symptoms had a second injection failure rate of 44%, compared to a 13% rate in those without symptoms of voiding dysfunction. CONCLUSIONS: Most failures of endoscopic correction are associated with mound shifting. The presence of a perfect mound does not predict success. Dysfunctional voiding predicts a lower success rate after a second injection.

Endoscopic management of vesicoureteral reflux in women presenting with pyelonephritis.

PURPOSE: Vesicoureteral reflux is not usually considered a major cofactor in acute pyelonephritis in women. However, there is a subset of individuals in whom reflux must be considered in the evaluation of acute pyelonephritis. We sought to evaluate the effectiveness of endoscopic treatment for vesicoureteral reflux in this subset of patients. MATERIALS AND METHODS: We retrospectively reviewed the records of 13 female patients presenting with clinical pyelonephritis between 2001 and 2005. All of these patients had either a history of vesicoureteral reflux in childhood or a family history of reflux, or had previously undergone surgery for reflux. All patients underwent voiding cystourethrogram and dimercapto-succinic acid renal scan as part of the evaluation. RESULTS: Of the 13 individuals evaluated 9 had vesicoureteral reflux. Of these patients 5 had been operated on previously for vesicoureteral reflux, 2 had a strong family history of reflux and 2 had reflux as a child with documented resolution. Six of the 9 patients with reflux exhibited renal scarring on dimercapto-succinic acid renal scintigraphy. Endoscopic correction of reflux was done in all 9 patients and was successful in 8, as shown on voiding cystourethrogram at 3 months postoperatively. One patient required a second procedure, which was successful. Only 1 patient has had a subsequent episode of clinical pyelonephritis, and voiding cystourethrogram following treatment again revealed resolution of reflux. CONCLUSIONS: There is a subset of women presenting with acute pyelonephritis in whom vesicoureteral reflux is a risk factor. When documented, vesicoureteral reflux can be managed effectively with endoscopic treatment.

Sexual function following bowel vaginoplasty.

PURPOSE: We review our 23-year experience with bowel vaginoplasty, with particular attention to postoperative quality of life and sexual function. MATERIALS AND METHODS: We reviewed the records of 57 patients who underwent bowel replacement vaginoplasty between 1980 and 2004. A total of 42 patients had the Mayer-Rokitansky syndrome, of whom 6 had varying forms of intersexuality, 6 had undergone surgery for pelvic malignancy, 1 had aphallia, 1 had cloacal exstrophy and 1 was the survivor of a conjoined twin separation. Replacement vaginoplasty was done using sigmoid colon in 39 patients, ileum in 9 and cecum in 9. Followup ranged from 18 months to 24 years, with a mean of 8.8 years. Outcome was evaluated by retrospective chart review, and the FSDQ, a validated, IRB approved instrument, was used to evaluate postoperative sexual function. RESULTS: Among the 57 patients postoperative sexual function was evaluated in 44, 9 were lost to followup and 4 were considered too young for evaluation. Of the 44 patients 36 responded to the FSDQ, 6 refused and 2 were unable to complete the questionnaire adequately. Of the 36 patients who responded 15 were married and 31 were sexually active. On a scale of 0 to 5, 28 patients (78%) reported sexual desire, 33% sexual arousal, 33% sexual confidence and 28 (78%) sexual satisfaction. In addition, 20 patients (56%) reported frequent orgasms, 8 (22%) occasional orgasms and 8 (22%) no orgasms. A total of 32 patients (89%) reported adequate lubrication for intercourse and 2 reported dyspareunia. Two of the 36 patients performed home dilation and required estrogen suppositories. A total of 34 patients used home douching and 20 required pads for mucus production. CONCLUSIONS: It appears that isolated bowel segments provided excellent tissue for vaginal replacement. For technical reasons we believe that colonic segments, particularly sigmoid, are preferable to small bowel. Sexual function following bowel vaginoplasty appears to be adequate and durable.

Endoscopic treatment with dextranomer/hyaluronic acid for complex cases of vesicoureteral reflux.

PURPOSE: The surgical correction of primary vesicoureteral reflux (VUR) is highly successful. This success decreases in more complex cases and often involves reoperation and increased morbidity. We present our experience with the use of subureteral injection of dextranomer/hyaluronic acid (Dx/HA) in complex cases of vesicoureteral reflux in which open surgery would have been indicated. MATERIALS AND METHODS: Between October 2001 and July 2003, 72 patients 9 months to 31 years old (mean age 5.6 years) underwent subureteral injection of Dx/HA for complex VUR at our institutions. Dx/HA was injected submucosally within the intramural ureter (modified STING) in most cases. A guidewire was used to manipulate the ureteral orifice and a retrograde ureterogram was used to delineate the anatomy in selected cases. The average volume of injected material was measured for each ureter. Renal sonography was performed to determine if hydronephrosis was present. At 3 months fluoroscopic voiding cystourethrograms were used to evaluate for the presence of VUR. RESULTS: A total of 93 ureters were treated in 55 girls and 17 boys. All cases were considered to be complex as 17 had persistent reflux after open surgery (7 megaureters repairs, 2 extravesical repairs, 7 intravesical reimplants and 1 blind ureter), 11 had persistent reflux and neurogenic bladder, 7 had ectopic ureters to bladder neck, 6 had bilateral Hutch diverticulum, 6 had persistent stump reflux, 5 had ureterocele after puncture or incision, 15 had duplications, 1 had the prune belly syndrome, 2 had posterior urethral valve following resection, 1 had epispadias and 1 had urogenital sinus. The average maximum reflux grade was IV. An average of 1.1 cc (range 0.4 to 2) was injected per ureter. Of the patients 69 had 3-month followup results. The overall success rate was 68% after 1 implantation (47 of 69). CONCLUSIONS: Submucosal intraureteral implantation with Dx/HA corrected complex vesicoureteral reflux in 68% of patients. In all of these patients open surgery would have potentially been difficult. The use of fluoroscopy and/or guidewires is a useful adjunct in these cases. We believe that this minimally invasive approach is warranted as an initial step in the management of complex cases of VUR before resorting to more difficult open surgical procedures.

Organ-confined primitive neuroectodermal tumor arising from the kidney.

Primitive neuroectodermal tumor (PNET) of the kidney is a rare entity with high malignant potential. Of the reported cases of renal PNET, patients presented with metastatic disease and had a poor response to therapy. The authors describe a rare case of an organ-confined primary PNET arising from the kidney in a 16-year-old girl who presented with vague abdominal pain. Tumor behavior and treatment modalities are discussed.

The cost-effectiveness of endoscopic injection of dextranomer/hyaluronic acid copolymer for vesicoureteral reflux.

PURPOSE: Vesicoureteral reflux is a risk factor for progressive renal damage associated with urinary tract infection. Mild to moderate reflux is routinely treated with long-term antibiotic prophylaxis to prevent recurrent infections and open surgical reimplantation for breakthrough infections despite antibiotic therapy. Endoscopic subureteral injection of implant material is a therapeutic alternative to long-term prophylaxis and open surgery but its widespread use in the United States has been prevented by the lack of a stable implant material. Dextranomer/hyaluronic acid copolymer has been shown to be a safe, effective and durable implant material and was recently approved in the United States. We estimate the effect on costs and cure rates of introducing endoscopic injection with dextranomer/hyaluronic acid copolymer as a treatment alternative in the United States. MATERIALS AND METHODS: We constructed a model that mimics current clinical practice of vesicoureteral reflux treatment for 6 years, and incorporates spontaneous resolution and surgical intervention rates obtained from 2 long-term followup studies. The treatment algorithm was established using medical data from the literature, and clinical management practices from a Delphi survey of 27 pediatric urologists and nephrologists across the United States. Endoscopic injection was introduced into the model as replacement to surgery or alternative to long-term antibiotic prophylaxis. The effectiveness of dextranomer/hyaluronic acid copolymer was calculated from 140 patients (208 ureters) with grade III reflux treated in a clinical study of 221 children in Sweden. RESULTS: With current practice, the average cost per patient in 6 years was 6,640 US dollars and 23.5% of patients continued to have reflux. Replacing open surgery with endoscopic injection led to similar cure rates (22.2% failures) but costs were reduced to 5,522 US dollars. When injection was performed after 1 year of antibiotic therapy failure rates were reduced to 8.5% but costs increased to 7,644 US dollars. CONCLUSIONS: Our results show that a persistent approach to endoscopic surgery can be expected to result in overall success that equals or exceeds open surgery at a lower cost. This finding is particularly true if open reimplant is reserved for patients with high grade or persistent vesicoureteral reflux.

Buccal mucosa grafts for hypospadias surgery: long-term results.

PURPOSE: We review the long-term results of buccal mucosa grafts used as part of secondary hypospadias repair. MATERIALS AND METHODS: We evaluated 47 patients for 10 years and analyzed long-term results of buccal mucosa grafts for hypospadias repair. Of the 47 patients 40 have been followed for more than 3 years. RESULTS: The overall complication rate was 32% (13 of 47 cases). All complications occurred in the first 6 months following surgery, and the complication rate was significantly lower in the last 7 years of the series (19%) compared to the first 3 years (60%) (p = 0.01). All 3 patients in this series with a preoperative diagnosis of balanitis xerotica obliterans had a significant postoperative complication. CONCLUSIONS: Buccal mucosa appears to be a durable source of nongenital tissue for urethral replacement. Attention to detail in terms of graft harvest, graft preparation and graft fixation helps to avoid major postoperative complications. Onlay grafts appear to be preferable to tube grafts, and patients with the diagnosis of balanitis xerotica obliterans would appear not to be candidates for 1-stage urethral reconstruction using buccal mucosa.

Vesicoureteral reflux: a new treatment algorithm.

Vesicoureteral reflux (VUR) affects about 1% of all children and carries an increased risk of pyelonephritis and long-term renal impairment. There are several approaches to the treatment of VUR: antibiotic prophylaxis (conservative treatment), open surgery, and endoscopic treatment. For many patients, endoscopic treatment cures VUR with a single procedure, eliminating the need for long-term antibiotic treatment and avoiding the trauma of a major surgical procedure. The choice of material for endoscopic treatment is of key importance, and, until recently, all available materials were associated with concerns regarding safety and efficacy. Emerging data demonstrate that dextranomer/hyaluronic acid (Dx/HA) copolymer has good long-term safety and efficacy in treating VUR. A new treatment algorithm is, therefore, proposed, recommending that most children with persistent VUR (longer than 1 year) be offered endoscopic treatment with Dx/HA copolymer as an alternative to prolonged antibiotic prophylaxis or open surgery.