The ´Overlooked´ Cause of Vesicoureteral Reflux in Children - Urethral Abnormalities

Purpose: To emphasize the significance of urethral abnormalities as the cause of vesicoureteral reflux in children. Materials and Methods: Current literatures were evaluated and the data in my laboratories were added. Results: Vesicoureteral reflux in boys which is more common in neonates and infants, has the tendency of quicker spontaneous resolution compared to girls in spite of its bilaterality and high grade. On the other hand, vesicoureteral reflux in girls, more commonly found after the first year of life, shows slower spontaneous resolution than boys although it shows lower grades when compared to boys. Such findings are attributed to sexual difference and the urethra is suspected to play an important role. The urethra influences the bladder function through sphincter to bladder reflex during the filling phase, and urethra to bladder reflex during the voiding phase. Cobb's collar which is an obstructive urethral lesion in males, is supposed to disappear after a short existence during fetal or neonatal period. However, if it causes severe obstruction or fails to disappear, it is suspected to result in the typical male type of vesicoureteral reflux caused by voiding dysfunction and increased intravesical pressure created by obstruction itself and urethral instability. Meanwhile, urethral abnormalities in girls such as mucosal web or female hypospadias causes vaginal voiding leading to dysfunctional voiding after toilet training and consequently results in vesicoureteral reflux through bladder instability, increased intravesical pressure and urinary tract infection as well as urethral instability. Conclusions: Since the meaning of surgery in vesicoureteral reflux, in view of kidney preservation, is becoming limited to the extent of recognizing the merit of surgical correction as merely discontinuing prophylactic antibiotics, studies of urethra in children with vesicoureteral reflux is another filed in (pediatric) urology which requires more active research and treatment.ope

An Analysis of Major Causes of Surgical Failure Using Bähren System in Intraoperative Venography During Varicocelectomy

Purpose: In young patients with varicocele, preservation of the internal spermatic artery may be advantageous for catch-up growth, but it may also increase the likelihood of treatment failure. Intraoperative venography reduces the likelihood that unsealed veins will remain after varicocelectomy. We analyzed the characteristics of remnant veins visualized through intraoperative venography to investigate the cause of surgical failure in artery-sparing varicocelectomy (ASV). Materials and methods: We retrospectively analyzed clinical characteristics and outcomes of patients aged 18 years or younger who underwent varicocelectomy with intraoperative venography from January 2005 to December 2017. During varicocelectomy, intraoperative venography was performed to distinguish veins from other structures. Any unsealed veins that were discovered were ligated and classified using the Bahren system. Results: One hundred and sixty-two patients underwent intraoperative venography: 153 cases (94.4%) were for primary varicocelectomy, and 9 cases (5.6%) were for repeat varicocelectomy. Open varicocelectomy was performed in 105 cases (64.8%), and laparoscopic varicocelectomy was performed in 57 cases (35.2%). Venography revealed remnant veins after the first ligation in 51 cases (31.2%), 46 (90.2%) and 5 (9.8%) of which were Bähren types 3 and 4, respectively. Five patients (3.1%) experienced varicocele recurrence, classified as persistence in 1 patient (0.6%) and relapse in 4 patients (2.5%). Conclusion: Remnant collateral veins of the internal spermatic vein (ISV) (Bahren type 3) are the most common cause of failure in ASV. In a few patients, an external spermatic vein merges with the ISV at a higher level (Bahren type 4) and is unidentifiable without venography.ope

CYP2C19 Polymorphisms and Smoking Status Affects Responsiveness to the Platelet P2Y12 Receptor Antagonist Clopidogrel

Background: The “comparison of triflusal and clopidogrel effects in secondary prevention of stroke based on cytochrome P450 2C19 (CYP2C19) genotyping (MAESTRO)” study was a prospective, multicenter, randomized, open-label, and blind genotype trial. We performed a subgroup analysis of the MAESTRO study to explore the relationship between VerifyNow P2Y12 assay with regard to CYP2C19 polymorphisms and smoking status in patients with non-cardiogenic ischemic stroke who underwent clopidogrel treatment. Methods: For the study, patients treated with clopidogrel and who underwent VerifyNow P2Y12 assay was selected from the MAESTRO study. Results: Of the 393 patients in 18 hospitals, 256 (65%) patients in 12 hospitals were entered for this subgroup analysis. P2Y12 reaction unit (PRU) was significantly lower and percent inhibition (% INH) was higher in the current smoking group than in the nonsmoking group (p<0.001). The same results were also observed in the good genotype group when compared with the poor genotype group (p<0.001). Among the groups, significant lower PRU and higher % INH was demonstrated in current smoking with good genotype group. However, there was no difference in PRU and % INH between current smoking with poor genotype group and nonsmoking with good genotype group, suggesting that clopidogrel activity was concurrently related to CYP2C19 polymorphisms and smoking status. Conclusions: Regarding secondary stroke prevention, patients who were current smokers and had a poor genotype for clopidogrel metabolism may benefit from clopidogrel treatment similar to that in patients who were nonsmokers and had a good genotype.ope

Large Cell Calcifying Sertoli Cell Tumor of the Testis : Case Report with Ultrastructural Study

Large cell calcifying Sertoli cell tumor (LCCST) is a rare testicular tumor, usually occurring in young men before the age of 20. Ultrastructural study has been performed rarely demonstrating Sertoli cell features. We report a case of LCCST in a 7-year-old boy. A well-circumscribed yellowish-tan, 1.5-cm-sized mass was located within the left testicular parenchyma. The cut surface was somewhat resilient with multiple calcifications. On microscopic examination, the tumor was composed of large eosinophilic polygonal cells with abundant eosinophilic cytoplasm arranging in solid tubular and trabecular patterns, superficially mimicking Leydig cell tumor. However, there were multiple calcifications and the tumor cell nests were surrounded by PASpositive basement membrane. Ultrastructural examination revealed the features of the Sertoli cell with Spangaro's crystals. The right testis showed a normal appearance by ultrasonogram and there were no other clinical features associated with Carney syndrome.ope

The Prevalence and Risk Factors of Overactive Bladder in Korean Children: A Comparative Analysis according to Definition

PURPOSE: We wanted to estimate the prevalence and risk factors of overactive bladder(OAB) in Korean children who were 5-13 years of age, according to the definition of OAB. MATERIALS AND METHODS: A randomly selected cross-sectional study was conducted on 26 kindergartens and 27 elementary schools nationwide in Korea. There were 19,240 children; a parent was asked to complete the questionnaires, which included items about OAB and the children's voiding and defecating habits. OAB was defined as urgency with or without urge incontinence, and usually with an increased daytime frequency and nocturia(ICCS 2006, group A) or an increased daytime frequency(>8 times/day) and/or urge urinary incontinence with or without urgency (group B); its prevalence and associated factors were investigated. RESULTS: The response rate for the questionnaires was 85.84%. The overall prevalence of OAB was 16.59%(group A) and 18.79%(group B). For groups A and B, the prevalence of OAB decreased with age from 22.89% to 12.16% and from 40.44% to 9.60%, respectively(p=0.0001). The overall rate of wet and dry OAB was 26.97% and 73.03%, respectively. Compared to the normal group, the children with OAB had a higher prevalence of nocturnal enuresis(NE), constipation, fecal incontinence, a history of urinary tract infection and delayed bladder control in both groups A and B(p<0.05). The rate of increased daytime frequency and urge incontinence were 3.69% and 2.31%(p=0.009), and 26.97% and 14.78%(p=0.0001) in group A and for the non-OAB children, respectively; their prevalence in group A decreased with age from 5.04% to 3.06% and from 45.74% to 18.50%, respectively(p=0.0001). CONCLUSIONS: The overall prevalence of OAB in group A for Korean children 5-13 years of age was similar to that in group B. However, the range of prevalence in group B was much more variable than that in group A. NE, constipation, fecal incontinence, a history of urinary tract infection and delayed bladder control may be risk factors for OAB in children.ope

First-line Treatment Modality in Children with Complete Duplicating System Complicated with Ureterocele or Ectopic Ureter: Ureteropyelostomy

Purpose: A complete duplicated collecting system complicated with an ectopic ureter or ureterocele results in renal damage due to a ureteral obstruction or reflux. The clinical outcome of ureteropyelostomy in complicated complete duplicated collecting system was evaluated. Materials and Methods: 20 children received a ureteropyelostomy for either an ectopic ureter or ureterocele with a complete duplicated collecting system anomaly. The median age was 3.2 months. Of the children, 11 had ureteroceles including 7 cecoureteroceles, and 9 had ectopic ureters. The associated anomalies were 3 UPJ obstructions of the lower pole and 9 VUR. All received a ureteropyelostomy. The lower pole ureter was used as the common ureter except in 2 cases with a lower ureter in poor condition. A lower pole pyeloplasty was combined in 3 cases with UPJ obstructions of the lower pole. A distal ureteral stump was left open except in the cecoureterocele in order to prevent VUR. Their clinical courses were followed up with an ultrasonogram and 99mTc-DMSA scan. The median follow-up after surgery was 17.8 months. Results: A reduced upper pole hydronephrosis was observed in 19 patients and an improvement in the differential renal function was noted in 17 patients on the follow-up studies. All ureteroceles had either disappeared or were reduced in size. 7 patients showed an intermittent asymptomatic bacteriuria and 1 patient showed symptomatic UTI who required an ureteroneocystostomy during the follow-up. Conclusions: A ureteropyelostomy is recommended as a first-line treatment modality for patients with a complicated complete duplicated collecting system owing to the lower chance of secondary surgery, the prevention of deterioration in the bladder function and the possibility of early correction.ope

The Postoperative Prognosis of Ureteropelvic Junction Obstruction according to the Appearance of the Ureter of Preoperative Retrograde Pyelography

PURPOSE: Controversy still exists about the necessity for a preoperative RGP (retrograde pyelography) in UPJO (ureteropelvic junction obstruction), but no standard has been established. Therefore, to define the role of preoperative RGP in UPJO, the postoperative prognosis, using the appearance of the ureter in preoperative RGP, was studied. MATERIALS AND METHODS: Between Jan. 1996 and Oct. 2001, the radiological studies of 38 children (mean age: 10.66 months), out of 77 diagnosed with UPJO followed by pyeloplasty, were available for a retrospective review. The subjects were divided into three groups: -group A; UPJ (ureteropelvic junction) narrowing only, group B; multiple narrowing, and group C; a hypoplastic ureter, based on the findings of the preoperative RGP. The improvements in the hydronephrosis, according to the comparison between the preoperative and postoperative U/S (ultrasonography), performed at 6 and 12 months after the operation, were retrospectively analyzed. RESULTS: The number of patients in the groups A, B and C were 15 (16 renal units, one bilateral UPJO), 11 and 12 (13 renal units, one bilateral UPJO), respectively. There were no statistically significant differences in the degree of preoperative hydronephrosis (mean+/-S.D., p>0.5). The degree of hydronephrosis (mean+/-S.D.) found at the U/S 6 and 12 month follow ups were 2.00+/-0.63 and 1.63+/-0.50, 1.91+/-0.70, and 1.45+/-0.52 and 2.92+/-0.76 and 2.62+/-0.77 in groups A, B and C, respectively, with all showing improvements. There were statistically significant differences in the degree of improvement in group C compared to groups A and B (p<0.05). CONCLUSIONS: The current study has shown that hydronephrosis, with a hypoplastic ureter, has a tendency to improve more slowly than other types of ureteral narrowing. Therefore, if the long-term follow-up data show the same results, a preoperative RGP may play an important role in evaluating the postoperative prognosis of UPJO.ope

A Comparison of Surgical Morbidity and Postoperative Voiding Function in Infants and 1-2 year-old Children after Ureteral Reimplantation

Purpose: The advisability of early ureteral reimplantation in infants is controversial, and to our knowledge no long-term results are available. Whether early ureteral reimplantation in infants increases surgical morbidity, compared to ureteral reimplantation after the age of 1 year, was investigated, and the long-term voiding function after ureteral reimplantation evaluated. Materials and Methods: Between 1993 and 1999, 130 children underwent ureteral reimplantation at our institution. The diagnosis was a primary vesicoureteral reflux, obstructed megaureter and an ectopic ureter. Two groups of 64 children that underwent ureteral reimplantation were compared. Group 1 included children younger than 12 months at surgery and group 2 children those between 1 and 2 years. The long term results were evaluated with regard to surgical outcome, voiding function and urinary tract infection. An analysis of the voiding function included family interviews, uroflowmetry and post-void residual urine measurements. Results: Complete long-term data were available for 47 boys and 17 girls. In Group 1, there were no complications in 50 renal units (96%), while two had postoperative reflux, and underwent macroplastique injection. In Group 2, there were no complications in 35 renal units (97.1%), while one patient had postoperative reflux, which resolved spontaneously. No significant difference was noted in the postoperative post-void residual urine volumes between the two groups. Conclusions: In our samples, early ureteral reimplantation resulted in a technical success rate of greater than 95% and low postoperative morbidity, with the exception of urinary tract infection. Our data show satisfactory bladder emptying and normal uroflowmetry. When indicated, ureteral reimplantation can be performed safely in young children, without fear of damaging bladder function.ope

The Effects of Biofeedback in Urge Syndrome and Dysfunctional Voiding

PURPOSE: We wished to introduce the curative effect of biofeedback in children with urge syndrome and dysfunctional voiding, and examine the durability of effect and the difference in response to medication before and after biofeedback. MATERIALS AND METHODS: There were 15 patients with urge syndrome and 8 with dysfunctional voiding. Average age was 8.2 years old (range, 4-16 years). Pelvic floor relaxation biofeedback, voiding biofeedback, and intravesical biofeedback were enforced with 4-18 sessions (average, 7.4). We defined the patient with disappearance of more than 90% of symptoms as 'improved', disappearance of 50 to 90% as 'partially improved', and the rest as 'not improved'. We assessed the degree of improvement between groups, and changes in uroflowmetry, functional bladder capacity and response to medication after biofeedback. RESULTS: Nine (60%) of the 15 patients with urge syndrome and 4 (50%) of the 8 patients with dysfunctional voiding showed improvement, and the overall response rate was 56% (13 of 23 patients). The mean follow-up period was 7.6 months, and the therapeutic effect lasted for 5.1 months. Among the 13 patients who were refractory to medical treatment, 8 (61%) improved and 3 with partial improvement responded well to medication after biofeedback. There were significant improvements in uroflowmetry findings; the numbers of bell shape and discordant shape (fractionated, staccato) before and after biofeedback were 7, 14 and 19, 4, respectively. Functional bladder capacity was also improved significantly from 177ml to 236ml (p=0.014). CONCLUSIONS: Biofeedback is an effective and safe treatment modality in most patients with urge syndrome and dysfunctional voiding.ope

Proteomic analyses of molecular factors associated with obstructive megaureter dysfunction

Objective: The underlying pathophysiology of obstructive and refluxing megaureters is poorly understood. The current study investigated the molecular mechanisms of ureter dysfunction, identifying proteins via proteomic analyses. Materials and methods: Megaureter and normal ureter tissues were used to examine differentially-expressed proteins. Smooth muscle cells (SMCs) of obstructive megaureters were obtained from five patients that underwent open ureteroneocystostomy surgeries and five control patients with low-grade vesicoureteral reflux. SMCs were cultured in M199 medium supplemented with 10% fetal bovine serum and 1% antibiotics. Aiming to identify differentially-expressed proteins, protein spots separated by 2D gel electrophoresis were matched. They were then analyzed using PDQuest software and nanoflow LC-ESI-MS-MS. Results: In the current study, α-tropomyosin, a protein associated with the contraction and migration of SMCs, was selected from several analyzed proteins, investigating its relationship with megaureters. When TPM1 was artificially overexpressed in normal ureter SMCs, a significant change in morphology was observed. In addition, the rate of apoptosis was increased in transfected SMCs, compared to that in control SMCs. Conclusion: Abnormal overexpression of TPM1 in ureter SMCs may induce defects in contractility and increase apoptosis rates. Empty spaces caused by apoptosis may then be preferentially filled with connective tissues, rather than slowly migrating SMCs. As a result, contractility is reduced, leading to the development of a dilated ureter.ope