Early urodynamic findings after complete primary repair of exstrophy.

INTRODUCTION: Detrusor contraction in bladder exstrophy (BE) patients following reconstruction is poorly understood as there are few published studies assessing urodynamic findings in this population. Understanding the ability of the detrusor to contract in BE patients early after closure may be able to inform the longer-term management and potential for the development of future continence in this population. OBJECTIVE: We sought to evaluate early detrusor contraction using urodynamic studies (UDS) in children who had previously undergone complete primary repair of bladder exstrophy (CPRE). We hypothesized that a majority of children with BE would display the presence of normal detrusor contractile function after CPRE. STUDY DESIGN: A retrospective review of our prospectively collected database was performed for all patients with a diagnosis of classic BE who underwent primary CPRE between 2013 and 2017. From this cohort we identified patients with at least one post-operative UDS at 3 years of age or older who had undergone an initial CPRE. Our primary outcome was the presence of a detrusor contraction demonstrated on UDS. RESULTS: There were 50 children (31 male, 19 female) with CBE who underwent CPRE between 2013 and 2017.There were 26 (13 male, 13 female) who met inclusion criteria. Median age was 3.5 (IQR: 3.2-4.7) years at the time of UDS Sixteen of the 26 (61.5%) generated a sustained detrusor contraction generating a void, with a median peak voiding pressure of 38 cm H20 (IQR: 28-51). The median bladder capacity reached was 48 ml, which represented a median of 30% of expected bladder capacity. The median post void residual (PVR) for the entire cohort was 26 ml (IQR: 9, 47) or 51% (IQR: 20%-98%) of their actual bladder capacity, while the median PVR for those children with a sustained detrusor contraction was 18 ml (IQR: 5, 46) or 33% (IQR: 27%, 98%) of their actual bladder capacity. Intraoperative bladder width and bladder dome to bladder neck length did not correlate with the presence of voiding via a detrusor contraction (p = 0.64). DISCUSSION: We present the first study assessing early UDS finding of detrusor contraction in BE patients after CPRE. In our cohort, 61.5% of patients were able to generate a sustained detrusor contraction on UDS which is a higher percentage than has been reported in previous series. A difference in initial surgical management may account for these findings. CONCLUSION: At short term follow up, the majority of children in our cohort were able to produce sustained detrusor contractions sufficient to generate a void per urethra with a modest post void residual volume. Long-term follow-up and repeated UDS will be needed to track detrusor contractility rates, bladder capacities, compliance, post void residuals and ultimately continence rates over time.

Impact of bilateral ureteral reimplantation at the time of complete primary repair of bladder exstrophy on reflux rates, renogram abnormalities and bladder capacity.

INTRODUCTION: Bilateral ureteral reimplantation at the time of the complete primary repair of bladder exstrophy (BUR-CPRE) has been proposed and has demonstrated favorable outcomes in the past. However, the potential benefits, including prevention of vesicoureteral reflux (VUR) and renal scarring must be tempered with any risks of reimplantation, persistent VUR, and the potential for overtreatment. We aimed to determine the impact of BUR-CPRE on reflux rates, renogram findings and bladder capacity. METHODS: An IRB approved registry of children treated for bladder exstrophy epispadias complex (BEEC) during a long-term international collaboration hosted in a region with high prevalence of BEEC was queried. Children undergoing primary CPRE for bladder exstrophy (BE) were identified. Surgical procedure and outcome measures nuclear medicine dimercaptosuccinic acid (DMSA) scintigraphy scans, voiding cystourethrogram (VCUG), and urodynamic study (UDS) were assessed for presence and degree of VUR, renogram abnormalities, and bladder capacity. RESULTS: A total cohort of 147 patients with BEEC was queried; 52 children (37 males, 71%) underwent primary CPRE for BE between 2009 and 2019 at median age of 1.1 years (IQR 0.6-1.9 years) with median follow up 4.4 years (IQR 2.4-6.4 years). BUR-CPRE was performed in 22/52 (42%). After BUR-CPRE, children were less likely to have VUR (any VUR present in 9 of 20 with imaging (45%) compared to 23 of 26 with imaging (82%) in the CPRE alone group (p = 0.007)). VUR in the BUR-CPRE group tended to be unilateral and lower grade in comparison to the CPRE alone group. DMSA abnormalities were less common in the BUR-CPRE group (4/19 (21%) vs.12/27 (44%)), although the difference did not reach statistical significance (p = 0.1). At 4 years follow-up, the BUR-CPRE group had a larger bladder capacity (p = 0.016). DISCUSSION: After BUR-CPRE, children had a lower rate of VUR, and when present, VUR was more often unilateral and lower grade compared to the CPRE alone group. Fewer numbers of children in the BUR-CPRE group depicted DMSA abnormalities. No children developed obstruction after BUR-CPRE and none have undergone repeat reimplantation. We documented a larger bladder capacity at the time of maximum follow-up available (4 years)-but further data are needed to confirm this observation. CONCLUSION: BUR-CPRE decreases the incidence and severity of VUR after CPRE, but the clinical significance of this remains unclear. We are encouraged by these initial results, but since BUR-CPRE does not uniformly eliminate VUR, we continue to proceed carefully in the well selected patient.

Back to the future: The Cecil-Culp technique for salvage penile reconstructive procedures.

INTRODUCTION: Re-operative penile reconstruction is challenging and requires tension-free skin closure. The repair popularized by Cecil and Culp in the 1940s, using the scrotum to provide a temporary vascularized bed for complex hypospadias repairs, fell out of favor due to temporal trends towards single-stage repairs and concern for utilizing hair-bearing skin on the penile shaft. OBJECTIVE: It was hypothesized that a modified Cecil-Culp (CC) concept of penile scrotalization, leaving the penis attached to the scrotum for 1 year rather than 6 weeks as originally described, improves outcomes with this reconstruction for ventral skin deficiency or poor vascular support. METHODS: Institutional Review Board-approved registries were reviewed to identify patients who underwent a CC repair during 1987-2016 at two institutions. Cecil-Culp technique was utilized in multi-stage hypospadias complication repairs or for insufficient ventral penile shaft skin coverage. Anatomic abnormality, number and type of prior surgeries, and complications before and after CC were recorded. RESULTS: Thirty-nine patients underwent CC: 23 failed hypospadias repairs, three hypospadias after bladder exstrophy, 10 penile curvature following circumcision, and three with skin loss from trauma. Mean age at CC was 61.8 months (hypospadias), and 59.8 months (non-hypospadias). Hypospadias patients underwent a mean of 3.6 surgeries (range 1-9) prior to CC. Four of the 39 patients (10.3%) had perioperative complications after CC, including scrotal abscess, skin infections, and difficulty removing the urethral stent. Eight of 37 (21.6%) patients had longer-term complications related to their hypospadias repair, including fistulae, diverticula, dehiscence, and stricture. Mean time from CC placement to release was 345 and 473 days for hypospadias and non-hypospadias cases, respectively. There was no apparent scrotal skin transferred to the penile shaft at the final take-down. Mean follow-up was 22.3 months. DISCUSSION: Embedding the penis into the scrotum for added vascularity and ventral skin coverage has been used effectively in cases of the most tenacious fistulas and for significant skin loss and trauma. Limitations of this study were its retrospective approach at two institutions over an extended period of time by multiple surgeons, so patient selection and procedure may have varied. CONCLUSIONS: Modification of CC repair by delaying 9-12 months before CC take-down enhanced the benefits of a robust vascular bed for wound healing, and helped to avoid transfer of hair-bearing scrotal skin to the penile shaft. The CC technique is an important tool for penile reconstructive surgery of complex hypospadias repairs with inadequate skin, and for traumatic injuries.

Tunica vaginalis flap for salvaging testicular torsion: A matched cohort analysis.

INTRODUCTION: In testicular torsion, ischemia time from pain onset impacts testicular salvage. A tunica albuginea fasciotomy to relieve compartment pressure followed by a tunica vaginalis flap (TVF) may enhance salvage. OBJECTIVE: To define the optimal window of ischemia time during which TVF may be most beneficial to avoid orchiectomy. STUDY DESIGN: A retrospective cohort study of males presenting with testicular torsion at a single tertiary-care institution from January, 2003 to March, 2017. Ischemia time was defined as duration of pain from onset to surgery. Because TVF would be an option to orchiectomy, and it was found that ischemia time was longer in testicles that underwent orchiectomy, matching was performed. Cases of torsion treated with TVF were matched 1:1 with cases treated with orchiectomy on age at surgery, and ischemia time. Outcomes included postoperative viability, defined as palpable testicular tissue with normal consistency, and atrophy, defined as palpable decrease in size relative to contralateral testicle. Sensitivity analyses were performed restricting to the subgroups with postoperative ultrasound, >6 months' follow-up, and additionally matching for degrees of twist. RESULTS: A total of 182 patients met eligibility criteria, of whom 49, 36, and 97 underwent orchiectomy, TVF, and septopexy alone, respectively. Median follow-up was 2.7 months; 26% of patients had postoperative ultrasound (61% of TVF group). In the orchiectomy, TVF, and septopexy groups, respectively, median ischemia times were 51, 11, and 8 h, postoperative viability rates were 0, 86, and 95%, and postoperative atrophy rates were 0, 68, and 24%. After matching, 32 patients with TVF were matched to 32 patients who underwent orchiectomy. In the TVF group, postoperative viability occurred in 95% (19/20) vs 67% (8/12) of patients with ischemia times ≤24 and >24 h, respectively. Atrophy occurred in 67% (12/18) vs 83% (10/12) of these same respective patients. Sensitivity analysis by ultrasound and longer follow-up found similar viability results, although atrophy rates were higher. Additional matching for degrees of twist showed lower viability and higher atrophy rates for increasing ischemia times. DISCUSSION: Patients who presented with testicular torsion with ischemia times ≤24 h and who were being considered for orchiectomy may have benefitted most from TVF, albeit at high risk of atrophy. However, for ischemia times >24 h, TVF may still have preserved testicular viability in two-thirds of cases. A limitation was short follow-up. CONCLUSION: A TVF was a valid alternative to orchiectomy for torsed testicles, albeit with high testicular atrophy rates.

Genitourinary involvement and management in children with Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are devastating hypersensitivity disorders that cause epidermal cell death and can affect all epidermal surfaces, including the urethra, vagina, labial and scrotal skin. Despite the well-described ocular and orofacial manifestations of SJS/TEN, there is a paucity of reports on the genitourinary (GU) symptoms and their management. Specifically, consulting services often ask the pediatric urology team if it is safe to place a urethral catheter, but there is no data in the literature to help guide management. The present study sought to review all pediatric cases of SJS/TEN in a tertiary care hospital to determine the incidence and optimal management of GU manifestations, including the use of urethral catheters. METHODS: With IRB approval, cases of SJS and TEN that were managed as an inpatient between January 2008 and June 2015 were retrospectively reviewed in order to identify the extent of GU involvement/manifestations, the treatment provided, use of urethral catheterization and long-term follow-up or complications. RESULTS: Thirty-one patients (15 female, 16 male; age range 2-18 years) presented with SJS or TEN over the study period. Etiologies for SJS/TEN included mycoplasma infection (48%) and medications (45%). Incidences of GU manifestations at presentation and their management are shown in Summary Table. Overall, 74% of patients had genital involvement of skin lesions. In 12 cases (39%), urology consultation was obtained. Twenty patients (61%) complained of dysuria and one child had gross hematuria in the setting of meatal lesion. Petroleum jelly was used in the majority of patients. A urethral catheter was placed in eight patients (25.8%, four female, four male) with a range of duration of 7-23 days. No patient developed hematuria or any other complications (i.e. strictures or urinary symptoms) after catheter removal. One boy required lysis of penile adhesions in the short-term. One of each gender developed penile and labial adhesions on long-term follow-up that self-resolved. CONCLUSIONS: GU involvement in SJS/TEN occurred in almost three-quarters of patients and was managed conservatively like other skin/mucosal manifestations. Long-term sequelae were rare and urethral catheterization appeared to be safe, without any short-term or long-term complications.

Short-term outcomes of the multi-institutional bladder exstrophy consortium: Successes and complications in the first two years of collaboration.

INTRODUCTION/BACKGROUND: Bladder exstrophy is a rare diagnosis that presents major reconstructive challenges. To increase experience and proficiency in the care of bladder exstrophy (BE), the Multi-Institutional BE Consortium (MIBEC) was formed, with a focus on refining technical aspects of complete primary repair of bladder exstrophy (CPRE) and subsequent care. OBJECTIVE: Outcome measures included successful CPRE (absence of dehiscence), complications, and integrated points of technique and care over the short-term. STUDY DESIGN: Boston Children's Hospital, Children's Hospital of Philadelphia and Children's Hospital of Wisconsin alternately served as the host, with observation, commentary and critique by visiting collaborating surgeons. CPRE with bilateral iliac osteotomy was performed at 1-3 months of age. High-definition video capture of the surgery allowed local and distant broadcast to facilitate real-time observation and teaching, and recording of all procedures. RESULTS: From February 2013 to February 2015, MIBEC participating surgeons performed CPRE on 27 consecutive patients (22 classic BE, five epispadias). There were no dehiscences in 27 patients (0%, 95% CI 0-12.5%). Thirteen girls and 14 boys underwent CPRE at a median age of 2.3 months (range 0.1-51.6). One boy had a hypospadiac urethral meatus at CPRE completion. Hydronephrosis of mild or moderate grade was present postoperatively in eight girls and two boys. Additional results, per gender, are presented in the Summary table below. DISCUSSION: Absence of dehiscence in this cohort was comparable or compared favorably with the literature. However, several girls had significant obstructive complications following CPRE. The rate of bladder outlet obstruction (BOO) in girls was increased compared with published reports. A low complication rate was noted in the boys following CPRE, which was comparable to reports in the literature, and early signs of continence and spontaneous voiding were noted in some boys and girls. Limitations included variation in patient age at presentation, thereby introducing a wide age range at CPRE. Outcome data were limited by short follow-up regarding voiding with continence. CONCLUSION: This collaborative effort proved beneficial regarding significantly increased surgeon exposure to CPRE, refinement of CPRE technique, surgeon learning and expertise. Technical refinement of CPRE is ongoing.

Hypospadias: Are we as good as we think when we correct proximal hypospadias?

OBJECTIVE: Hypospadias surgery is a humbling art form. Although outcomes with distal hypospadias are favorable, recent publications have suggested that the complication rates are much higher than previously anticipated for proximal hypospadias. The present review examined the literature concerning proximal hypospadias, to explore some of the inadequacies and identify some of the reasons behind these shortfalls in the reported data. METHODS: A systematic review of the published literature was conducted using keywords relevant to proximal hypospadias and long-term outcomes. RESULTS: The literature for hypospadias was reviewed, and outcomes for distal vs proximal variants were compared. The quality of the literature for proximal hypospadias was examined, and the shortcomings that led to underreporting of the surgical outcomes were identified. Special focus was on the lack of standardized documentation, the subsequent inability to objectify the severity of the phenotype, and the underestimation of complications due to lack of long-term follow-up. There was also a great deal of variability in the utilized techniques, and the literature was filled with small case series from single institutions. To enable scientific assessment of outcomes, it is proposed that the following be implemented: acceptance and incorporation of standardized phenotype assessment scores in the pre-operative period, objective intraoperative hypospadias characterization, and postoperative score assessment. CONCLUSIONS: Treatment of proximal hypospadias is much less successful than the distal variant. A specialty wide commitment to standardize the hypospadias language is required to make advancement in surgical outcomes. Boys need to be followed through puberty into adulthood, and honest reporting of outcomes must be discussed so that surgical techniques for this complicated disease process can be advanced.

Genetic or pharmacologic disruption of the calcineurin-nuclear factor of activated T-cells axis prevents social stress-induced voiding dysfunction in a murine model.

OBJECTIVE: Social stress can suppress the voiding reflex, with resultant diminished voiding frequency and increased volumes. The calcineurin-NFAT (nuclear factor of activated T cells) pathway is important in memory development. It was hypothesized that interruption of the calcineurin-NFAT pathway might prevent social stress-induced voiding dysfunction. METHODS: Mice were subjected to social stress in an established resident-intruder model for 1 h, followed by 23 h of barrier separation. NFATc3, NFATc4 knockout (KO) and wild-type (WT) mice were studied. At two weeks, voiding patterns were collected; this was followed by sacrifice. Corticotropin-releasing factor (CRF) mRNA expression in Barrington's nucleus (BN) was determined by in-situ hybridization. RESULTS: Social stress decreased voiding frequency and increased voided volumes in WT strains. At baseline, NFATc3 KO mice showed decreased voids and increased volumes, while the NFATc4 KO mice resisted social stress. However, CRF mRNA increased in WT mice following social stress and was increased at baseline in NFATc3 KO mice. It was found that CRF mRNA did not increase following social stress in NFATc4 KO mice. The administration of CsA to WT mice normalized voiding patterns following social stress, albeit with no effect on CRF mRNA in BN. CONCLUSION: Disrupting the calcineurin-NFAT axis by either genetic or pharmacologic approaches confers resistance to the development of social stress-induced voiding and dysfunction.

The use of vesicostomy as permanent urinary diversion in the child with myelomeningocele.

PURPOSE: Treatment of the child with myelomeningocele presents the urologist with many challenges. While vesicostomies are usually used for temporary bladder drainage until continent reconstruction is performed, we have a population of postpubertal patients with myelomeningocele in whom vesicostomies have been preserved. We review our experience with these older children. MATERIALS AND METHODS: A search of our database of 350 patients with myelodysplasia identified 23 with urinary diversion accomplished by permanent vesicostomy. Those who had undergone vesicostomy after age 11 years were designated as group 1. Those who received a vesicostomy early in life that was maintained post puberty were designated as group 2. Indications for vesicostomy, upper tract status before and after vesicostomy, recurrent infections and complications were noted. Upper tract status was determined by serial ultrasounds during routine followup. RESULTS: Group 1 was comprised of 5 patients with mean age at vesicostomy of 17 years and a mean followup interval of 5.2 years. Group 2 was comprised of 18 patients with mean age of vesicostomy at 2.6 years and mean followup interval of 13 years. Hydronephrosis resolved in all children from both groups. Vesicostomy revision was required in 1 patient secondary to prolapse. Other complications included mild prolapse that did not require revision, stenosis requiring revision 5 months after the initial procedure and an early bilateral ureterovesical obstruction that resolved. Of the patients 33% had recurrent upper tract calculi. CONCLUSIONS: While the goal of achieving urinary continence is well worth striving for in the child with myelomeningocele, it is not realistic for all patients. We believe that permanent cutaneous vesicostomy is an acceptable alternative that the reconstructive surgeon should consider. This reliable and simple technique ensures safe decompression of the upper urinary tracts, while avoiding the complications of urinary diversion using segments of bowel.

Buccal mucosal grafts: lessons learned from an 8-year experience.

PURPOSE: We evaluated our 8-year experience with buccal mucosal grafts in complex hypospadias and epispadias repair. MATERIALS AND METHODS: We reviewed the records of 29 patients in whom a total of 30 buccal mucosal grafts were placed as part of urethral reconstruction between 1991 and 1999. At surgery 16 tubes and 14 onlays were constructed and 24 of 30 repairs involved the meatus. All patients were followed at least 6 months postoperatively (median 5.3 years). Beginning in 1995 meatal design was enlarged to a racquet handle shape and patients were asked to perform meatal self-dilation for 6 months postoperatively. RESULTS: Complications developed in 17 of our 30 cases (57%) and reoperation was done in 10 (33%). All complications were evident by 11 months postoperatively except 1 that presented as recurrent stricture disease at 3 years. Complications developed in 5 and 12 of 15 patients who underwent surgery between 1995 and 1999, and before 1995, respectively (p = 0.027). No patient has had meatal stenosis since 1995. Complications included meatal stenosis in 5 cases, stricture in 7, glanuloplasty, meatal and complete graft breakdown in 1 each, and fistula in 2. Onlays were more likely to result in stricture than tube grafts (6 of 14 cases versus 1 of 16, p = 0.034). CONCLUSIONS: The complication and reoperation rates of buccal mucosal grafts are 57% and 33% at 5 years of followup. Changes in meatal design and temporary postoperative meatal dilation have improved the outcome in the last 5 years. Buccal mucosa remains a good choice in patients who require extragenital skin for urethral reconstruction.

Constipation as a cause of scrotal pain in children.

Six boys with scrotal pain and constipation were seen at our hospital within the past 5 years. All boys had no clinical findings of structural or infectious derangements, and experienced relief of testicular symptoms after evacuation of the fecal mass. The association between constipation and scrotal pain has not been previously reported, and may represent direct neural stimulation or chronic inflammation of testicular structures in patients with dysfunctional voiding. Recognition of the association between constipation and subacute or chronic scrotal pain can guide the clinician towards appropriate therapy for these patients.

The decompensated detrusor V: molecular correlates of bladder function after reversal of experimental outlet obstruction.

PURPOSE: Calcium ion homeostasis has a significant role in smooth muscle function. Its regulation requires complex storage and release mechanisms via ion pumps and channels located within intracellular storage sites (sarcoplasmic reticulum) and at the plasma membrane. We have previously reported a dramatic loss of the 2 major sarcoplasmic reticulum proteins sarcoplasmic endoplasmic reticulum calcium magnesium adenosine triphosphatase (SERCA2) and the ryanodine sensitive ion channel, also called the ryanodine receptor, after outlet obstruction. In our current study we investigated the correlation of the expression of these 2 major sarcoplasmic reticulum components with bladder function recovery after the reversal of outlet obstruction. METHODS AND METHODS: Standard partial bladder outlet obstruction was created in adult New Zealand White rabbits. Voiding patterns were monitored 2 and 4 weeks postoperatively, and rabbits were selected for outlet obstruction reversal based on a voiding pattern consistent with a decompensated state, as indicated by a frequency of greater than 30 voids daily and an average voided volume of less than 4 cc. Bladder biopsy was done when outlet obstruction was reversed. Voiding performance was monitored postoperatively and the animals were sacrificed 2 weeks later. Voiding patterns and muscle strip studies enabled us to define 2 functional outcome categories after reversal, namely normal versus minimally improved. Microsomal membrane protein fractions were prepared from the same bladder tissues before and after reversal, and probed by Western blot analysis for SERCA2 and ryanodine receptor expression. RESULTS: Western blot analysis revealed a major loss of SERCA2 and ryanodine receptor expression at the time of reversal and biopsy. In 65% of bladders obstruction reversal resulted in a normalized voiding pattern with a recovery of ryanodine receptor expression that was 15% to 65% of control values. In contrast, in the 35% of bladders with persistent voiding symptoms there was minimal recovery of ryanodine receptor expression. SERCA2 expression increased slightly in each group after reversal but did not differ in bladders with normalized versus improved function. CONCLUSIONS: Bladder decompensation is highly associated with a loss of sarcoplasmic reticulum function. Furthermore, the decompensated detrusor recovers function after obstruction reversal, which is associated with the recovery of these sarcoplasmic reticulum components.

Abnormal germ cell development in cryptorchidism.

BACKGROUND: Previous studies suggest that two fundamental, probably androgen-dependent, steps in maturation of germ cells normally occur in the prepubertal testis: the disappearance of gonocytes (the fetal stem cell pool) and the appearance of adult dark spermatogonia (the adult stem cell pool) at 2-3 months of age and the appearance of primary spermatocytes (the onset of meiosis) at 4-5 years. Previous studies of small series of cryptorchid boys suggest that both steps are defective in undescended testes and to a lesser degree in descended testes contralateral to unilaterally undescended testes. The purpose of this study is to confirm the previous findings of defective germ cell maturation in a large series of boys with unilateral undescended testes. PATIENTS: Seven hundred and sixty-seven boys with unilateral cryptorchidism who had orchidopexy and bilateral testicular biopsies between birth and 9 years of age were studied. MATERIALS AND METHODS: Total and differential germ cell counts were performed on semithin histologic sections of the biopsies. The results from the undescended and contralateral descended testes were compared using the Wilcoxon signed-rank test and the Wilcoxon-Whitney-Mann U test. RESULTS: Gonocytes failed to disappear and adult dark spermatogonia failed to appear in undescended testes under 1 year of age indicating a defect in the first step in maturation at 2-3 months resulting in failure to establish an adequate adult stem cell pool. Primary spermatocytes failed to appear in undescended testes and appeared in only 19% of contralateral descended testes at 4-5 years of age indicating a defect in the onset of meiosis. CONCLUSION: Unilaterally undescended testes fail to establish an adequate adult stem cell pool which normally occurs at 2-3 months of age and fail to establish adequate meiosis which normally occurs at 4-5 years of age. Similar but less severe changes are seen in the contralateral descended testes. Defects in the two pubertal steps in germ cell maturation are associated with reduced total germ cell counts.

Hormonal therapy for the subfertility of cryptorchidism.

BACKGROUND: The subfertility of cryptorchidism correlates with severely reduced total germ cell counts in prepubertal testicular biopsies of undescended testes. Reduced total germ cell counts are associated with defects in the two prepubertal steps in maturation and proliferation in germ cells: first, the transformation of the fetal stem cell pool (gonocytes) into the adult stem cell pool (adult dark spermatogonia) at two to three months of age and, second, the transformation of adult dark spermatogonia into primary spermatocytes (meiosis) at 4-5 years. The defects in maturation are associated with blunting of the normal surges in gonadotropins and testosterone. Prepubertal treatment with gonadotropin-releasing hormones would theoretically trigger normal germ cell maturation and proliferation and thereby improve total germ cell counts and improve fertility. Prepubertal treatment of cryptorchidism with the GnRH analogue Buserelin has resulted in improved total germ cell counts and improved spermiograms. The purpose of this report is to describe the results of treatment of cryptorchidism with the GnRH analogue Naferelin. PATIENTS: Twelve boys with cryptorchidism, 6 unilateral and 6 bilateral, and severely reduced germ cell counts in testicular biopsies were treated with Naferelin following successful orchidopexy and bilateral testicular biopsies. Response of the total germ cell counts was assessed in follow-up bilateral biopsies within 5 months of completing the hormonal therapy. RESULTS: Eight of the 12 boys (5 of the 6 with unilateral and 3 of the 6 with bilateral cryptorchidism) showed improvement in the total germ cell counts in one or both testes. All 8 had a poor prognosis for fertility pretreatment and a good prognosis for fertility posttreatment. Of the 5 with unilateral cryptorchidism who improved, 2 showed improvement in both testes; and 3, only in the contralateral descended testes. All 3 of the boys with bilateral cryptorchidism who improved showed improvement in both testes. Testes with absence of germ cells and older patients tended to show no improvement. Of the 6 contralateral descended, 5 (83%) improved, and of the 18 undescended testes, 8 (44%) improved. CONCLUSIONS: In this preliminary study, Naferelin therapy appears to induce improvement in the total germ cell counts and the prognosis for future fertility in 75% of patients.

The decompensated detrusor IV: experimental bladder outlet obstruction and its functional correlation to the expression of the ryanodine and voltage operated calcium channels.

PURPOSE: Calcium ion homeostasis has a significant role in smooth muscle function. Its regulation requires complex storage and release mechanisms via ion pumps and channels located within intracellular storage sites (sarcoplasmic reticulum) and at the plasma membrane. A prominent component of the sarcoplasmic reticulum is the ryanodine sensitive ion channel which releases calcium from the sarcoplasmic reticulum into the cytosol. At the level of the plasma membrane the voltage operated calcium channel (dihydropyridine sensitive) serves to allow an influx of extracellular calcium. Our prior studies have shown a loss of sarcoplasmic endoplasmic reticulum Ca++Mg++ATPase expression following outlet obstruction. In this study we correlate ryanodine and voltage operated calcium channel protein expression with bladder function following partial outlet obstruction. MATERIALS AND METHODS: Standardized partial bladder outlet obstructions were created in adult New Zealand white rabbits, which were divided into control, sham operated and obstructed groups. Muscle strip studies further subcategorized the obstructed group into compensated (force greater than 50% of control) and decompensated (force less than 50% of control) and were correlated with in vivo determinations of voiding frequency and voided volumes. Microsomal membrane protein fractions were prepared from the same bladder tissue and were used for Western blot analysis using specific monoclonal antibodies. RESULTS: Increased voiding frequency and decreased voided volumes correlated with the definitions of compensated and decompensated. The Western blots revealed a near disappearance of ryanodine expression in the decompensated group with minimal changes in the expression of the voltage operated calcium channel. CONCLUSIONS: Bladder performance as measured in vivo and in vitro after outlet obstruction is influenced in part by smooth muscle cell ability to maintain calcium homeostasis via the sarcoplasmic reticulum. Bladder decompensation is highly associated with a loss of sarcoplasmic reticulum function with lesser changes taking place in those calcium regulatory proteins at the plasma membrane.

The histopathology of iatrogenic cryptorchid testis: an insight into etiology.

PURPOSE: Iatrogenic undescended testis may develop after inguinal hernia repair, presumably as a result of mechanical tethering of the testis or cord in scar tissue. Because some true cryptorchid testes appear to be completely descended at birth and later ascend during childhood, some iatrogenic undescended testes may be low lying undescended testes. To determine whether iatrogenic undescended testes may be unrecognized cryptorchid testes at herniorrhaphy we examined biopsies of iatrogenic undescended testes and the corresponding contralateral descended testis. MATERIALS AND METHODS: Between 1985 and 1999 bilateral testis biopsies were obtained at orchiopexy in 37 boys 1.5 to 11.8 years old who previously underwent inguinal hernia correction. Histomorphometric analysis of germ cell counts was performed on the undescended and contralateral descended testes, and compared to the count in bilateral biopsies of 37 age and position matched patients with true unilateral cryptorchidism. RESULTS: There were no significant differences in volume or total and differential germ cell counts in the undescended and contralateral descended testes in the study groups and age matched controls with primary unilateral cryptorchidism. The mean number of germ cells per tubule in the undescended testis in patients with a greater than 5-year interval from herniorrhaphy to orchiopexy was significantly decreased compared to those with an operative interval of less than 5 years (0.27 +/- 0.33 versus 0.93 +/- 1.4, p = 0.026). CONCLUSIONS: Some patients with iatrogenic undescended testis may have an unrecognized low cryptorchid testis. Careful physical examination before and after inguinal surgery is recommended. The early repair of iatrogenic undescended testis is warranted to prevent further damage.

Laser tissue soldering for hypospadias repair: results of a controlled prospective clinical trial.

PURPOSE: Laser tissue soldering has been shown to provide safe and effective tissue closure by creating an immediate leak-free anastomosis with minimal scar formation. We compared the results of laser tissue soldering and conventional suturing for hypospadias repair. MATERIALS AND METHODS: A consecutive group of 138 boys 4 months to 8 years old (mean age 15 months) was divided into a standard suturing (84) and a sutureless laser (54) hypospadias repair group. Urethral repair was defined as simple (Thiersch-Duplay or Snodgrass) and complex (onlay island flap or tube) in 101 and 37 cases, respectively. Laser tissue soldering was performed with 50% human albumin solder doped with 2.5 mg./ml. indocyanine green dye using an 808 nm. diode laser at 0.5 W. In the laser group sutures were used for tissue alignment only. At surgery neourethral and penile length, operative time for neourethral construction and the number of sutures or throws were measured. Postoperatively patients were examined for complications of wound healing, stricture or fistula. RESULTS: Mean patient age, urethral defect severity, type of repair, neourethral length and stenting time plus or minus standard error of mean were not significantly different in the 2 groups. Mean operative time was a fifth as long for laser tissue soldering in simple and complex hypospadias repair compared to controls (1.5 +/- 0.1 and 5.1 +/- 0.3 versus 8.5 +/- 0.8 and 26.7 +/- 1.7 minutes, respectively, p <0.001). The mean number of sutures used for tissue alignment in the laser group for simple and complex repair was significantly less than in controls (3.0 +/- 0.2 and 8.2 +/- 0.6 versus 8.5 +/- 0.8 and 23.2 +/- 1.5, respectively, p <0.001). All patients were followed a mean of 12 months (minimum 6, maximum 22). The complication rate was 4.7% in the laser group and 10.7% in controls with fistula in 2 of 54 cases, and fistula and meatal stenosis in 7 and 2 of 84, respectively. CONCLUSIONS: These preliminary results indicate that laser tissue soldering for hypospadias repair may be performed in almost sutureless fashion and more rapidly than conventional suturing. The ease of the laser technique and the lower complication rate in the laser group indicate that laser tissue soldering is an acceptable means of tissue closure in hypospadias repair.