Insulin-like 3 exposure of the fetal rat gubernaculum modulates expression of genes involved in neural pathways.

Insulin-like 3 (INSL3) signaling directs fetal gubernacular development and testis descent, but the actions of INSL3 in the gubernaculum are poorly understood. Using microarray gene expression profiling of fetal male rat gubernaculum explants exposed to 10 or 100 nM INSL3, significant changes in expression were identified for approximately 900 genes. Several of the genes showing the largest inductions regulate neuronal development or activity, including Pnoc (34-fold), Nptx2 (9-fold), Nfasc (4-fold), Gfra3 (3-fold), Unc5d (3-fold), and Crlf1 (3-fold). Bioinformatics analysis revealed BMP and WNT signaling pathways and several gene ontologies related to neurogenesis were altered by INSL3. Promoter response elements significantly enriched in the INSL3-regulated gene list included consensus sequences for MYB, REL, ATF2, and TEF transcription factors. Comparing in vivo gene expression profiles of male and female rat fetal gubernaculum showed expression of the Bmp, Wnt, and neurodevelopmental genes induced by INSL3 was higher in males. Using quantitative RT-PCR, the microarray data were confirmed, and the induction of Bmp3, Chrdl2, Crlf1, Nptx2, Pnoc, Wnt4, and Wnt5a mRNA levels were examined over a range of INSL3 concentrations (0.1-100 nM) in male and female gubernaculum. In both sexes, an increasing gene expression response was observed between 0.1 and 10 nM INSL3. These data suggest that INSL3 signaling in the fetal gubernaculum induces morphogenetic programs, including BMP and WNT signaling, and support other rodent data suggesting a role for these pathways in development of the gubernaculum.

Pediatric laparoscopic pyeloplasty: lessons learned from the first 52 cases.

BACKGROUND AND PURPOSE: The use of laparoscopy for pediatric pyeloplasty is increasing. We review our experience with our first 50 cases and describe the main technical points learned during this experience. PATIENTS AND METHODS: We retrospectively reviewed the charts of all patients who underwent laparoscopic pyeloplasties (LP) over a 4-year period (January 2004 to January 2008) at our institution. Patient demographics, operative details, hospital stay, outcomes, and complications were examined. RESULTS: Fifty-two patients underwent LP from for primary repair of ureteropelvic junction obstruction (UPJO). Thirty-six male and 16 female were operated on at an average age and weight (range) of 51.8 months (3 weeks to 216 months) and 20 kg (3.9-74.2 kg), respectively. Intraoperatively, 47/52 (90%) underwent retrograde ureteropyelography (RUPG), and 51/52 (98%) had a ureteral stent placed during surgery. Nine crossing vessels (17%) were identified at the time of surgery. The anastomoses were performed with a running absorbable suture. Operative time was 248 min (range 120-693 min). The average hospital stay was 3 days (range 1-7). A bladder catheter usually remained indwelling for 2 days and a perirenal drain for 3 days; they were removed before hospital discharge. The stent remained in place on average 39 days (range 11-127 d) and was removed with the patient under a brief general anesthetic. Anastomotic patency was seen in 51/52 (98%) patients determined by improvement on postoperative renal ultrasonography and/or resolution of symptoms. Mean follow-up was 20 months (range 3-50 mos). Complications included recurrence of UPJO necessitating redo LP (1), dislodgement of a nephrostomy (1), stent replacement (1), ileus (2), and vascular injuries treated laparoscopically (2). No patients needed conversion to open surgery. CONCLUSION: LP has supplanted open pyeloplasty at our institution. We have noted improved success by performing RUPG to define the anatomy and stent placement at the beginning of the case, using purple 5-0 or 6-0 poliglecaprone suture for the anastomosis and a 5-mm wide-angle lens for visualization. We found no disadvantages for the transperitoneal approach, although we find it necessary to leave a drain. With the increased use of LP in pediatric urology, we hope these observations from our experience will help improve the learning curve for others making this transition.

Genetic and environmental contributors to cryptorchidism.

Cryptorchidism is a common congenital anomaly that shows familial clustering and increased prevalence in first-degree relatives, suggesting that genetic factors contribute to the etiology. Animal models and some human data suggest that environmental exposures may also contribute to risk. Potential variables during development that may contribute to the occurrence of cryptorchidism in the genetically susceptible individual include maternal hormonal influences as well as other environmental factors that affect hormonal signaling. In a subset of affected males, genetic and/or environmental factors may also contribute to associated infertility and malignancy. This review will discuss the limited state of knowledge regarding the etiology of non-syndromic cryptorchidism. Non-syndromic cryptorchidism is a common and complex disorder of un known etiology with geographic and perhaps temporal variability (1,2). Although presumed to be multifactorial in etiology, few specific genetic or environmental factors have been clearly linked to the disease in man. Hormonal pathways that participate in testicular descent and the effects of chemical exposures on this process have been studied in animal models. In man (3-5) and animal strains with cryptorchidism (6,7), there is evidence for multilocus genetic susceptibility. However, despite promising gene candidates, few genomic variants have been linked to non-syndromic cryptorchidism. Humans are exposed to a wide variety of potentially anti-androgenic and/or estrogenic environmental chemicals, but the degree to which these may contribute to the pathogenesis of cryptorchidism is not clearly known. Potential factors that may contribute to the etiology of cryptorchidism are discussed.

Iatrogenic ureteral injury after laparoscopic cholecystectomy in a 13-year-old boy.

We present a report of a delayed ureteral injury after a laparoscopic cholecystectomy. The patient presented with one episode of gross hematuria after surgery. He was treated with ureteral stent drainage and did well with no long-term sequelae.

Ipsilateral ureteroureterostomy in the surgical management of the severely dilated ureter in ureteral duplication.

PURPOSE: Ipsilateral ureteroureterostomy for the surgical management of severely dilated ureter in ureteral duplication is well supported in the surgical literature but often not done. We evaluated our institutional experience with ureteroureterostomy in duplication anomalies to assess the feasibility and success of this procedure. MATERIALS AND METHODS: An 8-year retrospective review of the records of all patients with complete renal duplex anomalies was evaluated. Anatomical presentations, and operative and nonoperative treatment of these patients were evaluated. RESULTS: A total of 193 patients were identified with complete renal duplication. Associated anomalies included ureterocele in 24 patients, ectopic ureter in 38 and vesicoureteral reflux in 57. Of 193 patients 160 (83%) with duplex anomalies underwent surgical intervention with a total of 41 ureteroureterostomies performed in 39 patients with dilated donor ureters. A total of 11 ureteroureterostomies were performed primarily and 30 were performed in conjunction with ipsilateral ureteral reimplantation of the distal common segment below the ureteroureterostomy. Ten of the 39 patients had the contralateral side reimplanted for vesicoureteral reflux. In all children with ureteroureterostomy the anastomosis between the 2 ureters remained patent. Two of the 11 children who underwent ureteroureterostomy alone had de novo ipsilateral vesicoureteral reflux (1), which was treated with ureteral reimplantation, and subureteral injection (1). Two children who underwent concomitant ureteroureterostomy and reimplantation without indwelling stents had transient postoperative urinomas that required subsequent drainage. Additionally, 3 patients had persistent ipsilateral vesicoureteral reflux, which was treated with subureteral injection in 1 and observation in 2. One patient presented with transient ipsilateral urinary obstruction, which required percutaneous drainage and resolved spontaneously. CONCLUSIONS: In cases of ureteral duplication with a severely dilated ureter requiring surgical intervention ipsilateral ureteroureterostomy is a viable option for reflux and/or obstruction. The procedure is rapid and technically feasible, and it offers excellent cosmesis. In addition, ureteroureterostomy has minimal morbidity and it facilitates early hospital discharge.

Minimally invasive open renal surgery.

PURPOSE: Improved pediatric laparoscopic techniques and instruments have led to the increased popularity of laparoscopic pyeloplasty and nephrectomy at some centers. The recent trend has compared laparoscopic to open techniques to draw parallel conclusions from the adult literature that laparoscopic surgery in children offers the same advantages. Historically open renal surgery in the pediatric population has been done successfully but usually through more traumatic incisions. We present our experience with minimally invasive open renal surgery. MATERIALS AND METHODS: A retrospective review of the last 6 years was performed of consecutive open pyeloplasties for ureteropelvic junction obstruction and open nephrectomy for multicystic dysplastic kidneys and renal duplication anomalies at a tertiary hospital for children. Parameters evaluated were patient age at surgery, surgical incision size, operative time, hospital stay and the need for postoperative narcotics. RESULTS: A total of 135 patients underwent open renal surgery using an open retroperitoneal flank incision, including 66 younger than 1, 32 who were 1 to 5, 11 who were 5 to 10 and 26 who were older than 10 years. Mean +/- SD operative time was 101.4 +/- 44.7 minutes in patients younger than 1 year, 87.7 +/- 39.3 minutes in those 1 to 5 years old, 127.1 +/- 62.7 minutes in those 5 to 10 years old and 127.8 +/- 38.4 minutes in those older than 10 years. Incision size for the groups was 1.9 +/- 0.61, 1.9 +/- 0.72, 3.0 +/- 1.3 and 3.8 +/- 1.6 cm, respectively. The last 20 patients younger than 1 year who underwent open pyeloplasty had an incision of between 1 and 1.5 cm. Most incisions were performed through a posterior, subcostal muscle splitting approach. All patients received postoperative ketorolac. Supplemental narcotics were not required in any patients younger than 10 years. Of the patients 90% were discharged home in less than 23 hours. CONCLUSIONS: The minimally invasive approach to open renal surgery is a safe and effective treatment choice in pediatric urology. The procedure can be easily performed through a small incision with minimal morbidity, comparable operative time and excellent cosmesis without excessive postoperative pain issues, allowing early discharge home. Perhaps this refined open surgery technique should be the benchmark for comparing new techniques.

Presentation of fused vas deferens.

Transverse testicular ectopia is a rare condition that usually presents as a unilateral nonpalpable testis and a contralateral descended testis with an associated hernia. Currently, with the use of diagnostic laparoscopy, transverse testicular ectopia is found before groin exploration. We reviewed 2 cases that were referred to our institution. Both patients had a common vas deferens with proximal fusion. To our knowledge, a fused vas deferens has only been reported three other times in published reports. Our second case is unique in that this is the first time a common vas deferens has been reported outside of transverse testicular ectopia.

Congenital anomalies of the kidney and urinary tract (CAKUT): a current review of cell signaling processes in ureteral development.

OBJECTIVE: The objective of this review is to present a concise summary of the genetic signaling processes involved in abnormal mouse Wolffian development and their correlation to those abnormalities affecting ureteral development in children. MATERIALS AND METHODS: We performed an extensive review of the current literature pertaining to mouse Wolffian duct development and combined these findings with our own data. CONCLUSION: This article reviews embryological findings in mice with ureteral abnormalities and draws connections between the mouse anomaly and what is seen in children. A review of the current literature has led to the identification of a number of genes which may prove to be important in understanding the causes of these anomalies.

The minimally invasive open pyeloplasty.

BACKGROUND: The dismembered pyeloplasty is the operation of choice for ureteropelvic junction obstruction (UPJO). Recently, with the advent of improved minimally invasive techniques and equipment, laparoscopic dismembered pyeloplasty has gained popularity. We present our experience with a minimally invasive open pyeloplasty. MATERIALS AND METHODS: A retrospective review of the last 5 years of consecutive open pyeloplasties was performed with regard to age, surgical operative time, length of hospital stay, need for postoperative narcotics and surgical success. RESULTS: Seventy-four patients had a dismembered pyeloplasty using an open flank incision: 34 patients (<1 year), 13 (1-5 years), 7 (5-10 years) and 20 (>10 years). Mean surgical time for patients according to age was: <1 year, 109.4+/-36.4 min; 1-5 years, 105.5+/-37.4 min; 5-10 years, 131.1+/-76.4 min; >10 years, 134+/-37.8 min. Mean incision sizes for the respective groups were 2.01+/-0.50 cm, 1.93+/-0.73 cm, 2.71+/-1.55 cm and 3.5+/-1.58 cm. The last 20 patients under 1 year of age had incisions of 1-1.5 cm. The majority of incisions were via a posterior subcostal muscle splitting approach. All patients received postoperative ketorolac and acetaminophen. Supplemental narcotics were not required in any patient less than 10 years old. All patients were discharged in <23 h. Radiologic and/or symptomatic improvement was seen in 70/74 (95%) patients after surgery. CONCLUSION: The minimally invasive approach to open pyeloplasty is a safe and effective treatment choice for UPJO. In small children our technique can be easily performed through a small incision without excessive postoperative pain allowing for early discharge. Our results with a refined open surgical technique challenge the current trend in the literature that laparoscopic pyeloplasty techniques are superior with regard to cosmesis, length of stay and postoperative narcotic use.