Evaluating TIMP-2 and IGFBP-7 as a predictive tool for kidney injury in ureteropelvic junction obstruction.

A major challenge in the management of ureteropelvic junction obstruction (UPJO) is the selection of patients who would benefit from surgical treatment. Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) indicate renal cell stress and are associated with cell cycle arrest. The [TIMP-2] [IGFBP7] ratio (Nephrocheck®) has been recently applied in patients in intensive care units patients to predict the development of acute kidney injury. In this study, we evaluated the performance of these biomarkers performance to distinguishing obstructive hydronephrosis (HN) from non-obstructive HN. MATERIALS AND METHODS: Consecutive patients with UPJO were enrolled in this study. Urinary [TIMP-2] [IGFBP7] and clinical characteristics (hydronephrosis grade, differential renal function, and drainage half-time) were measured in the following groups: 26 children with obstructive HN at initial diagnosis (group 1A) and after six months of dismembered pyeloplasty (group 1B); 22 children with non-obstructive HN (group 2), and 26 children without any urinary tract condition, as the control group (group 3). RESULTS: Comparing the initial samples, [TIMP-2] [IGFBP7] had higher levels in the HN groups and lower levels in the control group; however, no difference was observed between the HN groups (obstructive vs. non-obstructive). After six months of follow-up, patients who underwent dismembered pyeloplasty showed stability in the urinary concentration of [TIMP-2] [IGFBP7]. All patients with [TIMP-2] [IGFBP7] higher than 1.0 (ng/mL)2/1000 had diffuse cortical atrophy on ultrasonography. CONCLUSIONS: We showed that urinary levels of urinary [TIMP-2] [IGFBP7] are higher in children with HN than controls. Nephrocheck® is not reliable in predicting the need for surgical intervention for pediatric patients with UPJO.

Can extended upper pole ureterectomy prevent ureteral stump syndrome after proximal approach for duplex kidneys?

INTRODUCTION: Symptomatic duplex kidneys usually present with recurrent urinary tract infection due to ureteral obstruction (megaureter, ureterocele or ectopic ureter) and/or vesicoureteral reflux. Upper-pole nephrectomy is a widely accepted procedure to correct symptomatic duplex systems with poor functioning moieties, also known as upper or proximal approach. The distal ureteral stump syndrome (DUSS) can be a late complication of this approach. There is no consensus upon the length of ureteral dissection and the better approach to symptomatic disease in duplex systems, so we aim to identify if extended ureteral dissection can prevent DUSS in top-down approach. MATERIALS AND METHODS: Forty-four consecutive patients with symptomatic duplex system were retrospectively classified into two groups: those with limited ureteral excision after heminephrectomy (HN) (group-1) and those with extended ureterectomy after HN (group-2). Patients were followed-up for at least 36 months regarding outcomes of distal ureteral stump. RESULTS: Overall complication was 20%. A total of 8 patients required unplanned further surgery in Group-1 (30%) whereas only 1 patient required unplanned surgery in group 2 (6%) (p=0.07). Subgroup analysis showed that Group-1 presented more DUSS requiring surgery during follow-up than group-2 (p=0.04). Factors possibly affecting complications incidence (such as ureterocele or ectopic ureter) did not differ between groups (p=0.72 and p=0.78). CONCLUSION: Upper pole nephrectomy should be performed with extended distal ureteral dissection to prevent ureteral stump complications.

Transperitoneal laparoscopic pyeloplasty in children: does upper urinary tract anomalies affect surgical outcomes?

OBJECTIVE: To assess the feasibility and outcomes of laparoscopic pyeloplasty in children with complex ureteropelvic junction obstruction (UPJO) and compare to children with iso-lated UPJO without associated urinary tract abnormalities. MATERIAL AND METHODS: Medical records of 82 consecutive children submitted to transperitoneal laparoscopic pyeloplasty in a 12-year period were reviewed. Eleven cases were con-sidered complex, consisting of atypical anatomy including horseshoe kidneys in 6 patients, pelvic kidneys in 3 patients, and a duplex collecting system in 2 patients. Patients were di-vided into 2 groups: normal anatomy (group 1) and complex cases (group 2). Demographics, perioperative data, outcomes and complications were recorded and analyzed. RESULTS: Mean age was 8.9 years (0.5-17.9) for group 1 and 5.9 years (0.5-17.2) for group 2, p=0.08. The median operative time was 200 minutes (180-230) for group 1 and 203 minutes (120-300) for group 2, p=0.15. Major complications (Clavien ≥3) were 4 (5.6%) in group 1 and 1 (6.3%) in group 2, p=0.52. No deaths or early postoperative complications such as: urinoma or urinary leakage or bleeding, occurred. The success rate for radiologic improvement and flank pain improvement was comparable between the two groups. Re-garding hydronephrosis, significant improvement was present in 62 patients (93.4%) of group 1 and 10 cases (90.9%) of group 2, p=0.99. The median hospital stay was 4 days (IQR 3-4) for group 1 and 4.8 days (IQR 3-6) for group 2, p=0.27. CONCLUSIONS: Transperitoneal laparoscopic pyeloplasty is feasible and effective for the management of UPJO associated with renal or urinary tract anomalies.

Reoperative Laparoscopic Ureteropelvic Junction Obstruction Repair in Children: Safety and Efficacy of the Technique.

PURPOSE: Failure after pyeloplasty for ureteropelvic junction obstruction in children may occur in up to 10% of cases. Therapeutic options include Double-J® stent placement, endoscopic treatment and reoperation. Laparoscopic and robotic reoperative modalities seem safe and efficacious, although pediatric series are limited in the literature. We report the largest known series of reoperative laparoscopic ureteropelvic junction obstruction repair in children and compare this approach to primary laparoscopic pyeloplasty. MATERIALS AND METHODS: We reviewed all children undergoing laparoscopic pyeloplasty at a single institution from 2004 to 2015. Reoperative laparoscopic ureteropelvic junction obstruction repair was compared to primary pyeloplasty. Groups were analyzed regarding demographics, operative time, complications, length of hospital stay and success, defined by improvement of symptoms, ultrasound and renogram. RESULTS: We identified 11 cases of reoperation (8 redo pyeloplasties and 3 ureterocalycostomies) and 71 primary pyeloplasties. Groups were not different in age, gender or weight. Median followup was 37 months. Median time between primary pyeloplasty and reoperation was 34 months. Median operative time was 205 minutes for the reoperative group and 200 for primary pyeloplasty (p = 0.98). Length of stay was longer in the reoperative group (p = 0.049), although no major complications were recorded in this group. All reoperative cases and 96% of primary pyeloplasty cases remained asymptomatic following surgery (p = 0.99). Postoperative improvement was similar for both groups on ultrasound (90% for reoperation vs 92% for primary pyeloplasty, p = 0.99) and renogram (80% vs 88%, p = 0.6). CONCLUSIONS: Laparoscopy seems to be safe and effective for management of failed pyeloplasty in children. Based on our data, reoperation is as safe and effective as primary pyeloplasty.

Laparoscopic Pyeloplasty in children with Horseshoe Kidney.

INTRODUCTION: Horseshoe kidney occurs in 1 per 400-800 live births and are more frequently observed in males (M:F 2:1). Ureteropelvic junction obstruction (UPJO) is commonly associated with horseshoe kidneys. The variable blood supply, presence of the isthmus and high insertion of the ureter contribute to this problem. CASE REPORT: An asymptomatic 6 year-old boy presented with antenatal hydronephrosis. Ultrasonography and CT scan demonstrated left UPJO associated with a horseshoe kidney. DMSA showed 33% of function on the left side. DTPA showed a flat curve and lack of washout. A left dismembered laparoscopic pyeloplasty was performed after identification of crossing vessels and abnormal implantation of the ureter. After one year, the child is asymptomatic. DTPA demonstrated a good washout curve. RESULTS: Our cohort consisted of six patients, five males and one female, with a mean age of 6 years (range 6m-17 years) and a mean follow-up of 3 years. Ureteropelvic junction obstruction was more common on the left side. Symptoms appeared only in 34% of the cases. Mean operative time was 198 minutes (range 120-270 minutes). Crossing vessels were common (observed in 50% patients). High implantation of ureter was seen in 67% patients and intrinsic obstruction in 83%. Surgical difficulties were found in two cases. Hospital stay was 4.3 days (3 to 6 days), with only one patient having a mild complication (pyelonephritis). All cases had clinical and radiologic improvement. CONCLUSION: Laparoscopic pyeloplasty is safe and feasible in children with UPJO in horseshoe kidneys, with good results and minimal morbidity.

Urethral duplication type influences on the complications rate and number of surgical procedures.

INTRODUCTION: Urethral duplication is rare. Characterized by the presence of two urethral channels. This anomaly presents a great variety of clinical findings that depend on the type of duplication that often is associated with other anomalies. MATERIAL AND METHODS: We report thirteen boys with urethral duplication managed in our institution between 1988-2015. Clinical findings, associated anomalies, treatment of urethral duplication and our results are described. Patients were classified according to Effmann classification. RESULTS: Mean patient's age was 38.3±34.7 months (3-136 months). Mean follow-up was 7.7±3.4 years (3y8m-14y2m). Type II A2 was the most common pattern (8/13 patients, 61.5%), followed by type IA (3/13 patients, 23%) and IIA1 (2/13 patients, 15.3%). The most frequent clinical manifestations were urinary tract infections (UTI) observed in 11/13 patients (84.6%) and anal urinary leakage, found in 7/13 patients (53.8%). Associated anomalies were found in 9/13 patients (69.2%). Required surgeries were 3.53±2.84 procedures per patient. Considering groups: Type IIA2 4.25±3.28, type IIA1 4±1.41 and type IA 1.33±0.57 needed procedures per patient. Complications rate were 0% for type IA, 50% for type IIA1 and 75% for type IIA2. CONCLUSIONS: Patients with incomplete duplication (type I A or I B) can totally be asymptomatic, with no need of surgical correction. Type IIA2 is the most complex form of duplication to correct and multiple procedures might be required because of the very hypoplastic orthotopic dorsal urethral tissue. Surgical treatment should be individualized and parents should be advised on complications and need of multiple surgeries according to urethral duplication type.

MMP9 overexpression is associated with good surgical outcome in children with UPJO: Preliminary results.

BACKGROUND: Ureteropelvic junction obstruction (UPJO) diagnosed prenatally occurs in 1:150 - 1:1200 pregnancies. Although many studies investigating the molecular changes of this obstructed segment have been performed, the underlying mechanisms are still unclear. The role of extracellular matrix (ECM) components remains controversial, and the investigations in the field of ECM changes, might help the better understanding of the pathogenesis of this common condition. The aim of the present study was to investigate for the first time in the literature whether MMP9 and its specific inhibitors, TIMP1 and RECK, are expressed in a reproducible, specific pattern in UPJ. METHODS: UPJO specimens were obtained from 16 children at the time of dismembered pyeloplasty due to intrinsic UPJ stenosis. Expression levels of the three genes (MMP9, TIMP1 and RECK) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Then correlated the expression levels of the genes according to grade study population that was divided in 2 categories according to Society of Fetal Urology classification, grade 3 (moderate) and 4 (severe). For DTPA we subdivided the childrens in 2 groups, obstructive (T 1/2 more than 20 min) and partial obstructive (T 1/2 between 10 and 20 min) and success in a surgery was defined as decrease in T 1/2 to less than 20 min, absence of symptoms, improving renal function and decreasing dilatation on successive exams. RESULTS: MMP9 was underexpressed and TIMP1 and RECK were overexpressed in children with obstructive DTPA but the differences were not statistically significant. Overexpression of MMP9 was higher among patients with severe grade of UPJ compared to those with moderate grade. Surprisingly expression levels of MMP-9 was three times higher in children who were successfully treated by surgery (n = 10) (p = 0.072), so those who were followed for at least 1 year after surgery and remained with improvement in renal function and decreasing dilation on intravenous urogram and TIMP-1 was underexpressed in 100 % of this cases (p = 0.00). CONCLUSIONS: We showed an increase in expression of MMP9 and a decrease in expression of TIMP1 in children who improving renal function and decreasing dilation after surgery. We believe that the higher expression of MMP9 in these cases can reflect an increase in degradation and remodeling process that could be used as a marker for surgical outcome.

Malignant paraganglioma in children treated with embolization prior to surgical excision.

BACKGROUND: Paragangliomas (PGL) are rare tumors derived from neural crest cells, whose origins may vary along the chain of the sympathetic nervous system. Such tumors are often characterized by secretion of catecholamines, but sometimes they are biochemically inactive, which makes diagnosis often challenging. Malignant paraganglioma is defined by the presence of this tumor at sites where chromaffin cells are usually not found or by local invasion of the primary tumor. Recurrence, either regional or metastatic, usually occurs within 5 years of the initial complete resection but long-term recurrence is also described. Malignancy is often linked to a SDHB mutation. Preoperative embolization has been applied in the surgical management of PGLs with the objective to decrease intra-operative blood loss and surgery length without complications. CASE PRESENTATION: We report two cases of patients with abdominal or pelvic malignant PGLs who have been treated surgically at our center after preoperative embolization. Surgery was a very challenging procedure with multiple surgical teams involved and embolization did not prevent major blood loss and intraoperative complications. Patients required adjuvant treatment with either chemotherapy or radiotherapy. CONCLUSIONS: Many studies in the adult population have established recommendations for the diagnosis and therapeutic management of PGL, but few studies concern the pediatric population. Because malignant PGL is more important in the pediatric population, screening and early diagnosis of PGL is advisable in children with genetic predisposing. Surgical resection is the mainstay of treatment, but a multimodal approach is often required due to the complexity of cases.  The role of preoperative embolization is not established and in our experience it has provided little benefit and major complications.

Long-term followup of a large cohort of patients with ovotesticular disorder of sex development.

PURPOSE: We present the followup of a large cohort of patients with ovotesticular disorder of sex development treated at a single tertiary center. MATERIALS AND METHODS: We reviewed the records of 20 patients with ovotesticular disorder of sex development. We retrospectively evaluated clinical and surgical characteristics. A prospective study was also performed, including evaluation of surgical results, gonadal function, sexual activity and voiding symptoms of these patients during adulthood. RESULTS: All patients had ambiguous genitalia, including 18 with a 46,XX karyotype and 2 with a 46,XX/46,XY karyotype. Gender assignment at birth was male in 13 patients and female in 7. Three females were later reassigned to the male gender. Bilateral gonadectomy was performed in 10 patients. Testicular tissue was preserved in 8 males and ovarian tissue was preserved in 2 females. Average followup was 25 years (range 4 to 46). Puberty started spontaneously in 14 patients between ages 11 and 14 years. Seven patients showed spontaneous puberty after conservative gonadal surgery and 4 required hormonal replacement during adulthood. The most frequent complications in males were urethral fistula in 6 and late urethral stenosis in 3. Two patients with urethral stenosis had symptoms 10 years postoperatively. One female presented with temporary dyspareunia. In adulthood 8 males and 2 females reported sexual activity. All male patients reported orgasm and 2 reported ejaculation. CONCLUSIONS: Male gender assignment was more prevalent. Long-term followup revealed adequate pubertal development and sexual activity. Complications involving the urethra developed frequently in male patients.

Novel minimally invasive abdominoplasty for selected cases of prune belly syndrome: Step-by-step technique description and clinical indications.

BACKGROUND: Prune belly syndrome (PBS) is characterized by the triad of abdominal flaccidity, bilateral undescended testicles and genitourinary tract anomalies. A variable spectrum of abdominal wall laxity is observed in PBS. We present the first case of a novel technique using a minimally invasive abdominoplasty to specifically address patients with localized abdominal wall weakness in PBS. CASE PRESENTATION: A two-years-old child with PBS presented with recurrent febrile urinary tract infections. Ultrasonography demonstrated a dysplastic right kidney associated with significant ipsilateral ureterohydronephrosis. Voiding urethrocystogram did not show vesicoureteral reflux and DMSA scan depicted a non-functioning right kidney. During laparoscopic right nephroureterectomy and first stage Fowler-Stephens bilateral orchiopexies, a significant right-sided lateral abdominal wall bulging was observed. A minimally invasive laparoscopic abdominoplasty was performed with a one-way running suture using an unabsorbable 2.0 prolene approximating the edges of the musculofascial defect. While undergoing the second-stage Fowler-Stephens orchiopexy, no bulging was observed. CONCLUSION: A minimally invasive abdominoplasty to improve abdominal wall lateral bulging in PBS was feasible and presented good cosmetic result. We anticipate that this technique can be applied for children with PBS with primary lateral abdominal wall bulging, employing one or more suture lines depending on the fascial defect size.

Neonatal Hydrocolpos in Bardet-Biedl Syndrome due to a Novel Frameshift Indel in the BBS10 Gene.

INTRODUCTION: Hydrocolpos, a rare condition characterized by cystic dilatation of the vagina, can arise from various etiologies, including isolated imperforate hymen and vaginal atresia. Genetic conditions, such as Bardet-Biedl syndrome (BBS), may also manifest with hydrocolpos as part of urogenital malformations. METHODS: We present a case of neonatal hydrocolpos associated with BBS. Sequencing of 19 BBS genes was performed to elucidate the genetic basis of the syndrome. RESULTS: Genetic analysis revealed a novel frameshift indel variant (c.1543_1546dup p.Thr516Argfs*7) in the BBS10 gene. This finding expands the spectrum of BBS mutations and underscores the importance of genetic evaluation in patients with hydrocolpos, particularly when associated with additional clinical features suggestive of syndromic etiology. CONCLUSION: Pediatric urologists should maintain a high index of suspicion for underlying genetic conditions, including BBS, in neonates presenting with hydrocolpos, given the potential for more severe associated complications such as renal and retinal diseases, obesity, and polydactyly.

Scrotal flap phalloplasty as temporary neophallus in infants and children with penile agenesis: Multi-institutional experience and long-term follow-up.

INTRODUCTION: Aphallia is a rare congenital disorder pertaining to genotypic males. Early surgical creation of a neophallus is recommended to reinforce the child's male gender-identity, favoring proper psychosexual development. Modern microsurgical techniques used to create a neophallus in adults are not recommended in children due to the invasiveness and complexity of the procedures, along with high complication rates. Scrotal flap phalloplasty is a simple and reproducible technique to create a temporary neophallus in prepubertal boys with aphallia. OBJECTIVE: We present a multi-institutional experience, ten years after the initial description of the scrotal flap phalloplasty (SFP) technique, in which a flap from the well-developed scrotum is used to build a temporary neophallus, without obvious scars in patients with aphallia. STUDY DESIGN: The records of surgical neophalloplasty for aphallia patients from 4 centers between 2011 and 2021 were reviewed. All patients had at least one year follow-up to assess for short and long-term complications. Age at initial operation, associated anomalies, and other related surgical procedures were analyzed. RESULTS: The post-operative aesthetic result in all patients was satisfactory and has been maintained in the long-term follow-up, with all patients presenting a cylindrical structure resembling an uncircumcised penis, without evidence of significant contraction or loss of length. (Summary Figure) DISCUSSION: Non-microsurgical neophalloplasty techniques in patients with penile agenesis are temporary procedures that help to establish the body image and preserve the psychosexual development of the patient with aphallia. These techniques do not involve tissue transplant from a distant region, and are simpler to perform, with less scarring at the donor sites. Due to significant donor scars and considerable morbidity and complexity associated with the definitive phalloplasty techniques, we created a simple, reproducible and straightforward procedure to serve as a temporary neophallus in young boys with aphallia. As affected patients usually have a well-formed scrotum with normal and orthotopic testicles, it is the ideal donor site for a temporary neo-phallus in childhood. Furthermore, other donor sites are preserved for a definitive phalloplasty. There are limitations to this study, as quality of life could not be assessed and psychological or gender-identity investigations have not been carried out. None of these children have reached puberty, and hence decision and outcomes of definitive neophallus reconstruction has not been considered to date. CONCLUSION: Scrotal flap phalloplasty is a minimally invasive, simple and reproducible technique used to create a temporary neophallus in boys with aphallia, while waiting for definitive reconstructive surgery after puberty.

Elevated plasma miR-210 expression is associated with atypical genitalia in patients with 46,XY differences in sex development.

BACKGROUND: Differences of sex development (DSD) is a term used for conditions in which the chromosomal, gonadal or phenotypical sex is atypical. 46,XY DSD patients frequently present undervirilized external genitalia. The expression of different miRNAs in many organs of the male genital system has been reported, and these miRNAs have been associated with testicular function and its disorders, but no description has been related to DSD conditions. This study aimed to evaluate the plasma expression of miR-210 in 46,XY DSD patients who presented atypical genitalia at birth. METHODS: Eighteen 46,XY DSD patients who presented atypical genitalia (undescended testis and/or hypospadias, bifid scrotum or micropenis) at birth and 36 male control individuals were selected. Plasma levels of miR-210 and reference miR-23a were measured using RT-qPCR and the data were analysed by the 2-ΔCt method. RESULTS: MiR-210 plasma levels were significantly higher in 46,XY DSD patients with atypical genitalia than in male control subjects (p = 0.0024). A positive association between miR-210 levels and the presence of cryptorchidism and hypospadias (p = 0.0146 and p = 0.0223) was found in these patients. Significantly higher levels of miR-210 were observed in patients with 46,XY DSD and cryptorchidism than in control subjects (p = 0.0118). These results are in agreement with previous literature reports, in which increased levels of miR-210 expression were observed in human testicular tissue from adult males with undescended testes in comparison with samples of descended testes. CONCLUSION: Our study showed a positive association between the presence of atypical genitalia and plasma levels of miR-210 expression in the group of patients with 46,XY DSD of unknown aetiology studied. These findings contribute to reveal a new perspective on the role of miRNAs in the development of male external genitalia and the broad spectrum of phenotypes presented by patients with 46,XY DSD.

Laparoscopic hidden incision endoscopic surgery (hides) nephrectomy VS. Traditional laparoscopic nephrectomy: Non-inferior surgical outcomes and better cosmetic results.

INTRODUCTION: The benefits of laparoscopic total nephrectomy in pediatric patients are well established. Traditional Ports placement (TPP) still follows Clayman's classic description: except for the umbilical scar, the other laparoscopic scars are exposed in the abdomen. Advances in robotic surgery permitted the development of HidES (hidden incision endoscopic surgery) technique, to obtain a better final cosmetic aspect with the scars located intraumbilically and in the hypogastric region, in an area easily hidden by underwear. As robotic surgery is related to higher costs and lacks availability, a pure laparoscopic HidES technique was developed. OBJECTIVES: 1.Evaluate safety and efficacy of pure laparoscopic HidES.2. Compare HidES with TPP nephrectomy series to assess non-inferiority and cosmetic outcomes. STUDY DESIGN: Twenty-one pediatric patients with symptomatic poor functioning kidneys (DMSA<10%) underwent HidES nephrectomy. Their intra and post-operative outcomes were recorded prospectively. HidES group was compared to an equivalent group of thirty-two patients who underwent TPP nephrectomy. RESULTS: There were no conversions to open surgery in the TPP or HidES groups. There was a significant difference in operative time between HidES (53.4min) and TPP (109.4 min), with p = 0.004 and the mean bleeding volume was 65.5 ml. There was no significant difference in bleeding between HidES (71 ml) and TPP (120 ml) (p = 0.06), no intraoperative complications and no complications above Clavien-Dindo II during the 6-week follow-up. Satisfaction reached 100% in HidES group, whereas in TPP satisfaction was 63% (p = 0.004). DISCUSSION: HidES benefit over TPP is to conceal visible scars above underwear, improving cosmetical outcome. A prospective HidES group was compared to a retrospective TPP database due to decreasing number of nephrectomies being performed, which is a limitation of our study. HidES surgeries were performed by pediatric urologists (associate staff) while TPP group surgeries were performed by PGY-5 urological residents assisted by the associate staff, which is a clear limitation and can explain shorter operative times for HidES. During HidES surgeries an improved visualization of the operative field by the inferior trocar positioning was noted, which helps the posterior dissection of renal pedicle. Previous published study comparing robotic TPP and HidES pyeloplasty showed equal results for both groups with cosmetic advantages. Objective satisfaction was assessed with statistically advantage in favor of HidES procedure, consonant with other evidence that supports the benefit of scar location in patient and parental satisfaction. CONCLUSION: HidES nephrectomy proved to be safe, feasible and not inferior to the traditional nephrectomy in experienced hands, with better cosmesis.

Urinary extracellular matrix proteins as predictors of the severity of ureteropelvic junction obstruction in children.

INTRODUCTION: Ureteropelvic junction obstruction (UPJO) particularly represents a challenge in regard to management, as not all hydronephrosis (HN) represent a kidney-damaging state. Urinary biomarkers have been proposed as noninvasive tools. Extracellular matrix (ECM) proteins are associated with tissue fibrosis in the setting of UPJO and is poorly explored. OBJECTIVE: To investigate whether urinary ECM proteins are useful to discriminate the severity of urinary obstruction on unilateral UPJO. STUDY DESIGN: Children with unilateral UPJO were prospective enrolled. Urinary (u) matrix metalloproteinases (MMP-1,-2,-9 and TIMP-1,-2) as well as clinical characteristics were measured in the following groups: 26 children with obstructive HN at initial diagnosis and after six months of dismembered pyeloplasty; 22 children with non-obstructive HN at diagnosis and after six months of observation; 26 children without any urinary tract condition, as the control group. Results were assessed statistically using for homogenous groups, a one-way analysis of variances (ANOVA) and for nonparametric groups, Mann-Whitney test or Kruskal-Wallis test was performed. ROC curves were performed. RESULTS: Baseline samples demonstrated a higher concentration of uMMP-1/Cr, uMMP-2/Cr, u-TIMP-1/Cr and u-TIMP-2/Cr in obstructive HN group; uMMP-9/Cr levels were higher in non-obstructive HN group and all studied biomarkers had lower concentrations for the control group. On follow-up, for the obstructive HN group, urinary concentration of uTIMP-1/Cr and uTIMP-2/Cr decreased, and uMMP-1/Cr, uMMP-2/Cr and uMMP-9/Cr increased when comparing preoperative to postoperative values. In the non-obstructive HN group, all proteins analyzed were stable after six months of observation. ROC curves analysis showed a promising diagnostic profile for the detection of obstructive HN for uTIMP-1/Cr (area under the curve -AUC-; of 0.692), uTIMP-2/Cr (AUC of 0.678) and for uMMP-2/Cr (AUC of 0.655). DISCUSSION: The severity of kidney obstruction could correlate with the urinary ECM proteins concentration in this study. This is concordant with prior studies demonstrating that a disruption of the balance of accumulation/degradation of the ECM proteins occur on obstructive uropathy. Limitations of our study include the older age of our patients and that these markers had no influence at all on the surgical decision. CONCLUSION: We demonstrate that obstructive HN have significantly higher uMMP-2, uTIMP-1 and uTIMP-2 concentrations. Particularly, uTIMP-2 levels were correlated to severity of obstruction and therefore, it might be a useful urinary biomarker to correctly allocate children with HN between surgical management vs follow-up. After pyeloplasty, uTIMP-1 and uTIMP-2 presented a progressive decrease postoperatively, which is also highly desirable for urinary markers.

Management of functioning pediatric adrenal tumors.

AIM: The aim of this study is to present our experience in the management of hormonally active adrenal tumors in children. MATERIAL AND METHODS: We did a retrospective chart review of all children with hormonally active adrenal tumors evaluated at the endocrinology clinic and operated at our institution between 1983 and 2019. RESULTS: There were 75 patients included in the study, 58 with adrenocortical tumors (ACTs) and 17 with pheochromocytomas (PCCs). Within the group of patients with ACTs, there were 41 females and 17 males. The mean age was 58.3 (SD: 87.9; range: 9-211) months. The clinical manifestation of the tumor's hormonal activity was virilization in 37 cases, Cushing syndrome in 5, and mixed in 16. A positive family history was present in 11 patients (18.9%). The mean tumor size was 48.2 (SD: 22.4; range: 7-120) mm. The pathological diagnosis was adenoma in 42 cases, carcinoma in 15 cases, and macronodular hyperplasia in 1. Median follow-up was 192 (range: 50-290) months. Tumor recurrence occurred in 6 patients (10.3%), and there were three disease-related deaths (5%). Within the group of patients with PCCs, there were 11 males and 6 females. The mean age was 146.7 (SD: 71.2; range: 60-216) months. A positive family history was present in 7 patients (41.2%). The mean tumor size was 36.6 (SD: 16.7; range: 7-120) mm. The pheochromocytoma was classified as benign in 15 cases and as malignant in 2. During a median follow-up of 180 (range: 127-300) months, recurrence was observed in 6 cases (35.3%) and disease-related death in 1 case (5.9%). CONCLUSIONS: Proper diagnosis and management at our referral center were associated with a high cure rate, even in cases of malignant tumors. Familial surveillance is highly recommended. LEVEL OF EVIDENCE: Level IV.

Long-term surgical outcome of masculinizing genitoplasty in large cohort of patients with disorders of sex development.

PURPOSE: We evaluated the results of masculinizing genitoplasty in a large cohort of patients with disorders of sex development treated at a single public tertiary center. MATERIALS AND METHODS: We evaluated 52 patients with 46,XY and 7 with 46,XX disorders of sex development with proximal hypospadias and genital ambiguity reared as males who had undergone surgery between 1965 and 2008. Mean +/- SD followup was 14.1 +/- 9.2 years and median age at last examination was 22 years, with 38 patients having reached adulthood. Morphological result and urinary stream were evaluated by a physician. Urinary and sexual symptoms, and satisfaction with surgical results were assessed by questionnaire. RESULTS: Mean penile length at diagnosis was compared between 46,XY patients and showed that those with 5alpha-reductase 2 deficiency had the shortest penile length (-5.4 +/- 1.2 SD). At the last clinical evaluation following surgical and hormonal treatment mean +/- SD penile length in 38 adults was 7.5 +/- 2.1 cm (range 4 to 12), corresponding to -4.3 +/- 1.3 SD (-6.5 to -1.5). All but 2 patients had penile length less than -2 SD. At that time mean penile length remained shorter in patients with 5alpha-reductase 2 deficiency (-5.4 +/- 1 SD) compared to those with testosterone production deficiency or indeterminate disorders of sex development (p <0.05). There was no statistical difference between mean penile length before and after treatment in all etiological groups (p >0.05). Morphological results were good in 43% of patients, fair in 54% and poor in 3%. The most common complications were urethral fistula (51%) and urethral stenosis (22%). Dribbling after voiding was the most frequent urinary symptom. Satisfaction with surgical results was reported by 89% of patients. Among adults 87% were sexually active, with 64% reporting normal sexual activity. CONCLUSIONS: Most patients with 46,XY disorders of sex development were satisfied with long-term results of masculinizing genitoplasty, although specific complaints about small penile length, sexual activity and urinary symptoms were frequent. New surgical approaches should be developed to ensure full satisfaction in adulthood among patients with disorders of sex development.

Gonadal Function and Reproductive System Anatomy in Postpubertal Prune-Belly Syndrome Patients.

OBJECTIVE: To gain insight into the causes of infertility in Prune Belly Syndrome (PBS) by evaluating reproductive system anatomy and gonadal function in a cohort of postpubertal PBS patients. METHODS: We contacted all PBS patients 14 years old or older treated and followed at our institution. Age at orchiopexy, type of orchiopexy (with or without ligation of gonadal vessels), testicular volumes and positions were evaluated. Pelvic magnetic resonance imaging (to assess prostate size, seminal vesicles, and vas) and hormonal profile were ordered. Sperm analysis and analysis of urine after masturbation were performed after informed consent. RESULTS: Fifteen patients were included in this study. Mean age was 19.2 years. Mean age at orchiopexy was 18 months. Fourteen patients (93.3%) had normal and orthotopic testes. Mean testicular volume was 6.9 cc. Eight patients collected semen, 5 of them (62.5%) had spermatozoa in the specimen and motile sperm was found in 4 (50%). Mean hormone levels were LH: 5.3 mg/dL, FSH: 6.9 mg/dL, testosterone 531 mg/dL. Magnetic resonance imaging revealed hypoplastic prostates in 66.6% and unilateral seminal vesicle absence in 66.6%. No vasal abnormality was noted. CONCLUSION: Patients with PBS may have normal sexual hormonal levels. Motile spermatozoa were found in half of the patients. Our study highlights a high prevalence of prostate and seminal vesicle abnormalities that may represent an important cause for their infertility.