Protein expression in vesicoureteral reflux: What about children?

PURPOSE: Pathogenesis of vesicoureteral reflux (VUR) which concerns improper embryonal ureteric bud development still remains controversial, despite current studies have revealed several candidate genes. In this study, we aimed to determine the protein expression of certain genes which might play role in the pathogenesis of VUR, in the resected ureterovesical junction segments. METHODS: The study group consisted of 19 children; 12(63%) girls, 7(37%) boys who had ureteroneocystostomy (UNC) operation; 3(15.7%) right sided, 7(36.8%) left sided, 9(47.3%) bilateral due to VUR. As a total, 28 ureterovesical junction segments were available for analysis of protein expressions of GDNF/RET, PAX2 and FGFR2 genes by their Western Blot analysis. RESULTS: Protein based expressions of FGFR2, PAX2 and RET were significantly lower than ß-Actin (p = 0.001, for all proteins). Correlation analyses between grade of reflux and protein expressions revealed no significant relations (p>0.05, for all proteins). When we grouped the patients into 2 groups as high grade (grade 4-5) and low grade reflux (grade 1-3) for convenient analyses, no statistically significant difference was found between groups (p>0.05, for all proteins). Renal units were also grouped according to differential functions (≥40% and <40%) obtained by renal scintigraphy and compared in terms of proteins' expressions. There was also no significant difference between two groups regarding FGFR2, PAX2 and RET band areas (p>0.05, for all proteins). CONCLUSION: Our study revealed decreased protein expressions of GDNF/RET, PAX2 and FGFR2 genes in the patients with VUR. Relation between clinical parameters and expression levels were statistically uncorrelated. Prospective studies of larger sample size are necessary in order to delineate the impact of certain proteins in the etiopathogenesis of VUR.

Relation between Cajal Cell Density and Radiological and Scintigraphic Outcomes in Patients with Ureteropelvic Junction Obstruction.

INTRODUCTION: In this study, we aimed to investigate the correlation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters in ureteropelvic junction obstruction (UPJO). METHODS: The study group consisted of 41 renal units (38 consecutive patients; 13 female and 25 male) surgically treated for UPJO. UPJ specimens from patients were immuno-stained with CD117 (c-kit) antibody for interstitial Cajal cells (ICCs). The relation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters was evaluated. RESULTS: The mean age of the patients was 8.52 ± 8.86 (0-35) years. The density of Cajal cells was defined in 2 groups for convenient analysis as 0-5 cells (low) in 19 (46.3%) patients and >5 cells (moderate-high) in 22 (53.6%). There was significant difference between the preoperative and postoperative anteroposterior diameters of the related kidneys in both Cajal groups (p = 0.001-low, p = 0.000-moderate-high) independent of Cajal cell density. Regression in hydronephrosis postoperatively was determined in both Cajal groups (77.8%-low, 64.7%-moderate-high); however, there was no difference between them (p = 0.39). Preoperative T1/2 was significantly longer in the low Cajal group (p = 0.02). Postoperative T1/2 decreased in both low (p = 0.000) and moderate-high (p = 0.001) Cajal groups, but no difference was found between them (p = 0.24). There was significant improvement in the kidney differential function after surgery in the low Cajal density group (p = 0.015) while there was no correlation between the scintigraphic success or improvement and Cajal cell density (p = 0.51). DISCUSSION/CONCLUSION: ICC deficiency/density could not be shown as a predictive factor for the determination of success rate of pyeloplasty. Despite the lack of any evidence for the degree of deficiency as an indicator for the severity of obstruction and prediction of surgical success, further studies are needed for confirmation.

Comparison of corporal plication for the correction of congenital penile curvature in pre-pubertal and post-pubertal patients: Does age matter?

We retrospectively reviewed and compared the results of corporal plication procedures for the correction of congenital penile curvature (CPC) between pre-pubertal and post-pubertal boys and find whether age matters in the success rates. We reviewed the records of 32 patients with CPC without hypospadias treated by simple plication near the 12 o'clock position between 1998 and 2018 in our clinic. Patients under 13 years of age and not had puberty yet were accepted as pre-pubertal. Residual curvature less than 10° during follow-up was accepted as a surgical success. The mean age of the pre-pubertal group was 8.3 (2-12) years, while 16.2 (14-21) for the post-pubertal patients. The mean follow-up was 38.7 (24-154) months in the pre-pubertal group and 45.1 (23-150) months in the post-pubertal group. The success rates of corporal plication in pre-pubertal and post-pubertal groups were 78% and 83% respectively (p = .753). The success rates of corporal plication were similar between pre-pubertal and post-pubertal boys. However, as the series was small further studies should be favoured to determine the effect of age on success rates.

Did our current initial treatment practice change after EAU/ESPU vesicoureteral reflux risk grouping?

BACKGROUND/PURPOSE: The "European Association of Urology (EAU) Guidelines on Vesicoureteral Reflux (VUR) in Children (September 2012)" established risk classification by analyzing and defining risk factors for each patient. In this study we aimed to investigate how our initial treatment procedures were affected by EAU/ESPU guideline vesicoureteral reflux risk grouping and to compare the early clinical results of treatments performed before and after the risk classification in our patients with VUR. MATERIALS AND METHODS: 334 renal units with regular clinical follow-up who were treated owing to VUR (vesicoureteral reflux) between years 2009 and 2017 were retrospectively reviewed. Preoperative clinical parameters such as grade and laterality of reflux, presence of renal scar, initial and follow-up treatments, findings of medical treatment and surgical procedures were analyzed. The initial medical and surgical methods were compared by categorizing patients according to risk groups before and after 2013. RESULTS: Mean age and follow-up duration were 71.4(6-216) months and 47(4-141) months, respectively. Among the preoperative parameters, only high EAU risk group (p = 0.01) and treating lower urinary tract symptoms (p < 0.001) were determining the postoperative success rates significantly, while age, sex, and presence of renal scar at DMSA were not affecting the success of treatment significantly. While no significant difference in medical and surgical treatment rates is observed after risk grouping system in low risk group, the percentages of patients who are treated with surgical methods initially were significantly decreased in moderate and high risk groups (p = 0.002 and p = 0.012, respectively). We determined that VUR risk grouping did not change clinical success significantly in all risk groups. CONCLUSIONS: Despite the fact that EAU/ESPU VUR risk classification changed our current practice in terms of initial treatment method, this different approach did not seem to affect early clinical success positively. There is still an absolute need for studies with larger sample size and long-term follow-up to reach more reliable results. TYPE OF STUDY: Therapeutic. LEVEL OF EVIDENCE: Level 4.

Factors Affecting the Success Rate of Percutaneous Nephrolithotomy in Paediatric Patients.

In this study, we aimed to determine factors affecting the success rate of percutaneous nephrolithotomy (PNL) in children. The series consisted of 41 consecutive children operated on by the same surgical team for renal calculi with PNL between June 2002 and May 2015 in our institution. A single calyx or pelvic stone was described as simple, while calculi located in more than one location (calyx and pelvis or more than one calices) or staghorn stones were described as complex. The procedure was deemed successful if the patient was completely stone-free (SF) or had residual fragments <4 mm. Thirty-four patients were found to be SF or had residual fragments <4 mm on the postoperative first day, thus the success rate was 82.9%. In complex stones, the success rate was significantly lower (45.5%) than simple stones (96.7%) (p < 0.001). The grade of hydronephrosis (Grade 0-1 vs. Grade 2-3) also had a negative impact on the success, with rates of 92.6% vs. 64.3%, respectively (p = 0.022). Previous urological procedure history on the same side yielded a success rate of 58.3%, whereas the success rate in the primary patients was 93.1% (p < 0.001). The localization of the stone (complex vs. simple), degree of hydronephrosis, and history of previous urological procedures were found to be the factors that affected the success of the paediatric PNL.

Changes in Cajal cell density in ureteropelvic junction obstruction in children.

INTRODUCTION: Congenital ureteropelvic junction obstruction is one the most common causes of neonatal hydronephrosis. The etiology of the ureteropelvic junction (UPJ) obstruction has not been clearly established. The presence of a hypoplastic, adynamic ureteral segment is thought to be the major cause of an UPJ obstruction. OBJECTIVE: We evaluated the distribution of Cajal cells using immunohistologic methods coupled with light microscopy of the UPJ tissues in obstructed and normal UPJs. STUDY DESIGN: The study group consisted of 19 patients who underwent pyeloplasty for UPJ obstruction. Twelve patients who had been operated on for oncological indications constituted the control group. The sections were stained immunohistochemically using CD117 (c-kit) antibody; the numbers of CD117 (+) interstitial cells of Cajal were counted in 10 consecutive high-power fields under the light microscope and the cell density was determined for each case. RESULTS: The mean age of the cases who underwent dismembered pyeloplasty and the control group were 116 ± 116 months (14 male, 5 female; 6-420 months) and 279 ± 312 months (9 male, 3 female; 24-948 months) (p = 0.1), respectively. The mean interstitial Cajal cell number in the UPJ obstruction and the control groups were 2.37 ± 2.19 and 24.5 ± 9.73, respectively (p < 0.0001). Thirteen (68.4%) patients had very few, five (26.3%) patients had few, and one (5.3%) patient had many Cajal cells in the UPJ obstruction group. In the control group, all patients had more than seven cells per high-power field. DISCUSSION: We found that in cases of UPJ, obstruction the numbers of interstitial Cajal cells were decreased, being either absent or significantly reduced. Although data about the motility are currently not sufficient, the decrease in the number of Cajal cells in patients with UPJ highlights that they might be responsible for the initiation, coordination, and conduction of peristaltic activity along the pelvicalyceal system. Improvement and enhancement of contraction waves arising from the upper urinary system depend on interstitial cells of Cajal, which are the pacemaker cells in smooth muscles. We think that a decreased number of interstitial cells of Cajal have a close relationship with changing ureteral motility when we compare our UPJ obstruction cases with the limited data in the literature. CONCLUSION: Further investigations on these cells will probably give detailed information about the neurophysiology of the urinary system and the diseases that cause congenital hydronephrosis.

Urodynamic disorders and renal scarring in pediatric patients with nonmonosymptomatic nocturnal enuresis.

BACKGROUND/AIM: In nonmonosymptomatic nocturnal enuresis (NMNE), the incidence of organic abnormality and urodynamic disorder is more frequent than the general population. The aim of this study is to identify urodynamic disorders and renal scarring in children with NMNE. MATERIALS AND METHODS: This study evaluated the urodynamic disorders and renal scarring of a total of 30 patients who were diagnosed with NMNE. A video-urodynamic test and Tc-99m dimercaptosuccinic acid renal scintigraphy were applied. RESULTS: Records of 605 patients who had been diagnosed with enuresis were analyzed, and 215 (33.5%) of them had been diagnosed with NMNE. Thirty patients older than 6 years old with NMNE were included in the study. Detrusor overactivity was identified in 10 patients. Bladder capacity was low in 5 patients and bladder compliance was low in 2 patients. Renal scarring was identified in 1 patient. Unilateral vesicoureteral reflux was found in 4 patients. CONCLUSION: Bladder function disorder is also a significant risk factor for the development of renal scarring, besides other risk factors. Organic abnormalities are seen more often in patients with NMNE than patients with monosymptomatic nocturnal enuresis, so urodynamic studies should be remembered for patients with NMNE.

Factors affecting complication rates of ureteroscopic lithotripsy in children: results of multi-institutional retrospective analysis by Pediatric Stone Disease Study Group of Turkish Pediatric Urology Society.

PURPOSE: We evaluated factors affecting complication rates of ureteroscopy for pediatric ureteral calculi. MATERIALS AND METHODS: We retrospectively evaluated 642 children who underwent ureteroscopy at 16 Turkish centers between 2000 and 2010. Semirigid ureteroscopy was used with various calibers to treat 670 ureteral units in 660 sessions. Complications were evaluated according to the Satava and Clavien classification systems. Univariate and multivariate analyses were done to determine predictive factors affecting complication rates. RESULTS: A total of 367 females and 265 males were studied. Mean±SD patient age was 90.2±51.4 months (range 4 to 204). Mean±SD stone size, operative time and postoperative hospital stay were 8.9±4.7 mm, 45.8±23.8 minutes and 1.8±2.8 days, respectively. At a mean±SD followup of 13.3±17.6 months 92.8% of patients were stone-free and efficacy quotient was 90.3%. Complications, which occurred in 8.4% of patients (54 of 642), were intraoperative in 25 (Satava grade I to II in 22), early postoperative in 25 (Clavien grade I to II in 23) and late postoperative in 4 (all grade III). While operative time, age, institutional experience, orifice dilation, stenting and stone burden were statistically significant on univariate analysis, multivariate analysis revealed that operative time was the only statistically significant parameter affecting the complication rate. CONCLUSIONS: Semirigid ureteroscopy is effective, with a 90% stone-free rate and efficacy quotient. Most complications are low grade and self-limiting. Our results confirm that prolonged operative time is an independent predictor of complications, and should be considered when choosing and performing the treatment modality.

Vincristine-induced peripheral neuropathy and urinary bladder paralysis in a child with rhabdomyosarcoma.

Vincristine commonly induces peripheral neuropathy but rarely causes voiding dysfunction. In this report, we describe a case of neurogenic bladder and peripheral neuropathy caused by the neurotoxic effect of vincristine and documented by urodynamic testing and electromyography. Neurologic evaluation aided in monitoring and understanding this problem.

Repair of hypospadiac urethral duplication with dismembered urethroplasty.

Urethral duplication is a complex and rarely seen anomaly with three anatomic variants: epispadiac (dorsal), hypospadiac (ventral) and Y-type. Here we report an 11-year-old male patient with hypospadiac urethral duplication who presented with daytime urinary incontinence and dribbling, urethral stricture and possible obstructive uropathy. After endoscopic treatment of the stricture in the ventral (dominant) urethra, urethral reconstruction was done anastomosing the ventral (dominant) and dorsal (non-dominant atretic urethra) in a dismembered fashion.

The impact of pelvicaliceal features on problematic lower pole stone clearance in different age groups.

AIM: Our aim was to evaluate the impact of pelvicaliceal variables in pediatric and adult age groups who underwent SWL for lower caliceal calculi. METHODS: 25 pediatric and 78 adult patients treated with extracorporeal shock wave lithotripsy (SWL) between 1996 and 2004 were enrolled into the study after exclusion of patients with hydronephrosis, major renal anatomic anomalies, non-calcium stones, history of recurrent stone disease and previous renal surgery. Lower pole infundibulopelvic angle (IPA), infundibular length (IL), infundibular width (IW) and pelvicaliceal volume were measured from pre-SWL intravenous urography. The pelvicaliceal stone load (PSL) index implicating the stone burden of each patient described as the relationship between stone volume and total estimated pelvicaliceal volume for stone-bearing kidney was also calculated. RESULTS: Sixty-eight percent of adult and 80% of pediatric patients became stone-free after SWL. The statistical insignificance between PSL index (p=0.097) of two groups shows that both groups shared a similar stone burden. According to SWL outcome, mean IPA values of stone-free and residual patients were 46.85 degrees and 30 degrees in pediatric group, respectively (p=0.01), whereas these values were 48.08 degrees and 43.06 degrees in the adult group, respectively (p=0.352). In the pediatric age group, stone-free and cumulative success rates increased with increasing IPA but this correlation was statistically insignificant (p: 0.263). CONCLUSIONS: Lower caliceal anatomy has a higher impact on stone clearance after SWL in pediatric patients and urologists can expect better SWL outcomes from pediatric population with solitary lower caliceal stone than adults under the same conditions.

Assessment of urinary symptoms in children with dysfunctional elimination syndrome.

OBJECTIVE: This study was organized to form a symptom scale for diagnosis and assessment of urinary and bowel symptoms in children with dysfunctional elimination syndrome (DES). METHODS: The study group included 81 children presented to our clinic with symptoms of DES like enuresis, abnormal voiding, urinary tract infection and urgency, between January 2003 and February 2004. Age matched 102 children with no history of urological complaints were randomly recruited from a public school as control group. Children with isolated, mono-symptomatic nocturnal enuresis were not taken to the study. All children and parents were requested to fill a 35-item questionnaire related to symptoms of DES. After statistical analysis, questions from the initial form that had a P-value <0.05 and an area under curve (AUC) value >0.6 were selected to form a final scale. RESULTS: The mean ages for study and control groups were 8.7 +/- 2.5 and 8.3 +/- 2.2 years, respectively (P = 0.236). The final scale was composed of 15 questions. The cut-off score for the presence of DES was determined as 7.5 (sensitivity 85.2%, specificity 93.1%, AUC value = 0.943) for the total population. When only the male population were concerned the cut-off score was 4.5 (sensitivity 93.8%, specificity 78%, AUC value = 0.913) while the cut-off score for the female population was 7.5 (sensitivity 87.7%, specificity 94.2%, AUC value = 0.953). CONCLUSION: Providing objective assessment of symptom severity, formation of a validated scoring system for children with DES might be a good tool for diagnosis, confirmation of treatment results and follow up. It might also be useful for screening purposes.

Evaluation of sexual function in women with overactive bladder syndrome.

INTRODUCTION: Of late, little data is available concerning factors affecting female sexual function. In the present study, we evaluated the effects of overactive bladder (OAB) syndrome symptoms on female sexual function. MATERIALS AND METHODS: 40 patients with OAB symptoms and 40 age-matched women as a control group were evaluated using the Female Sexual Function Index (FSFI) for sexual function. According to the presence of urge incontinence, women with OAB were also divided into wet and dry groups. After completion of the forms, groups were compared. RESULTS: Although scores of all domains of FSFI (desire, arousal, lubrication, orgasm, satisfaction, pain and total) in the OAB group were found to be lower than in the control group, only 'desire' was found to be significantly different (p = 0.035). The FSFI scores of the OAB-dry and OAB-wet group were similar to each other. CONCLUSION: The results indicate that there is a trend toward lower sexual function scores in women with OAB compared to controls.

Bladder augmentation: Review of the literature and recent advances.

Bladder augmentation is an important tool in the management of children requiring reconstructions for urinary incontinence or preserving of the upper urinary tract in congenital malformations. We reviewed the literature and evaluated the long-term results of enterocystoplasty in the pediatric age group and summarized techniques, experimental options and future perspectives for the treatment of these patients. For this purpose, a directed Medline literature review for the assessment of enterocystoplasty was performed. Information gained from these data was reviewed and new perspectives were summarized. The ideal gastrointestinal (GI) segment for enterocystoplasty remains controversial. The use of GI segments for enterocystoplasty is associated with different short and long-term complications. The results of different centers reported in the literature concerning urological complications after enterocystoplasty are difficult to compare because of the non-comparable aspects and different items included by different authors. On the other hand, there are more and more case reports about cancer arising from bowel segments used for bladder augmentation in recent publications.Although bladder reconstruction with GI segments can be associated with multiple complications, such as metabolic disorders, calculus formation, mucus production, enteric fistulas and potential for malignancy, enterocystoplasty is unfortunately still the gold standard. However, there is an urgent need for the development of alternative tissues for bladder augmentation.

Minimally invasive treatment of ureteral calculi in children.

A retrospective analysis was done to determine the efficacy of shock wave lithotripsy (SWL) and ureteroscopy in the treatment of paediatric ureteral calculi. We reviewed the records of 67 (35 boys, 32 girls) children (71 ureters) admitted to our clinic for treatment of ureteral calculi during 1990-2005. The initial treatment method was SWL in 80.3% (57 ureters), ureteroscopy in 11.3% (eight ureters) and open surgery in 8.5% (six ureters) of the renal units. The mean age of the patients was 10.67 +/- 4.4(1-16) years. The stone-free rates after SWL for upper, middle and lower ureteral calculi were 74.1, 100 and 75.9%, respectively. Increased stone diameter (P = 0.014) and/or burden (P = 0.002) were found to be significant factors that had an adverse affect on the stone-free rate after SWL while the success rates of SWL were independent of location. Including six patients (seven ureters) with failed SWL, a total of 14 patients (15 renal units) subjected to ureteroscopy for lower ureteral calculi yielded a stone-free rate of 93.3%. Thus, the overall stone-free rates after SWL, ureteroscopy and open surgery were found to be 75.4, 93.3 and 100%, respectively. Depending on the stone burden, SWL might be a good option for initial treatment of most ureteral calculi in children. Ureteroscopy offers a high success rate for lower ureteral calculi, including SWL failures.

Parameatal cyst of urethra: a rare congenital anomaly.

We report a case of parameatal urethral cyst in a 15-year-old boy which is a very rare congenital anomaly. The cyst recognized at infancy but the boy presented to our clinic at the age of 15 when the mass was grown enough to cause spraying of urine and poor cosmesis. Complete excision of the cyst with total removal of the epithelium is the required for treatment and prevention of recurrence.

Prolapse of a simple ureterocele presenting as a vulval mass in a woman.

A 48-year-old woman presented with a large vulval mass after prolapse of a ureterocele. Her past excretory urogram showed a filling defect (cobra head appearance) in the bladder related to a single-system ureterocele on the left. The mass was manually reduced back through to the urethra under sedation and a urethral catheter was inserted. The anterior wall of the ureterocele was resected transurethrally for definitive treatment.

Factors affecting the success rate of extracorporeal shock wave lithotripsy for renal calculi in children.

The aim of the study was to analyse factors affecting the success rate of extracorporeal shock wave lithotripsy (ESWL) in children with renal calculi. We performed a retrospective analysis reviewing records of 85 (40 female, 45 male) children (89 renal units) subjected to ESWL for treatment of renal calculi during 1990-2005 in our department. As 4 patients had bilateral calculi and 19 children (21 renal units) had renal stones at more than one different site, each location was analysed separately for convenience. The mean age of the patients was 10.3+/-4.6 (2-16) years. The stone-free rates for renal pelvis, lower, middle and upper caliceal calculi were 70, 62, 50 and 73%, respectively. A higher rate (33%) of insignificant fragments (< or = 4 mm) was noted for lower pole calculi. Increased stone diameter (P=0.0001) and burden (P=0.04) were found as the most significant factors that adversely affect the stone-free rate for pelvis renalis calculi, whereas an acutely oriented infundibulum and/or a long lower infundibulum (P=0.005) were unfavourable factors for clearance of lower caliceal stones. The stone-free rate in children with multiple calculi was 48%, while 29% of the renal units had retained fragments. ESWL is a good initial option for treatment of most of the renal calculi < 2 cm except in the presence of unfavourable lower caliceal anatomy. Increased stone burden, multiple stones, staghorn calculi, narrow lower infundibulopelvic angle and long lower infundibulum are factors that adversely affect the clearance rate.

Pelvicaliceal anatomical variation between stone bearing and normal contralateral kidneys--does it have an impact on stone formation in pediatric patients with a solitary lower caliceal stone?

PURPOSE: We aimed to investigate the probable effect of pelvicaliceal anatomical differences between stone bearing and normal contralateral kidneys on the etiology of stone formation in children with a solitary lower pole caliceal stone. MATERIALS AND METHODS: We reviewed the clinical records of 25 pediatric patients who underwent SWL for a solitary lower caliceal stone and 15 healthy pediatric patients who served as controls. Lower pole IPA, IL and IW, together with other caliceal variables obtained from the pelvicaliceal anatomy of the stone bearing and contralateral normal kidneys of patients with urolithiasis, and both kidneys of the control group were measured based on excretory urography. Also, total pelvicaliceal volume for both kidneys was calculated. RESULTS: Mean LIPAs of stone bearing kidneys compared to the normal contralateral kidneys was more acute, equal and wider in 52%, 16% and 32% of the patients, respectively. Mean pelvicaliceal volumes of the stone forming and normal kidneys were 1,553.8 mm(3) (range 242 to 7,107) and 581.0 mm(3) (90 to 2,662), respectively, and there was statistical significance only in pelvicaliceal volumes between the stone bearing and contralateral normal kidneys (p <0.001). CONCLUSIONS: Our results reveal that IPA, IL and IW of calices do not have an effect on stone formation in pediatric patients. However, large pelvicaliceal volume seems to be a significant risk factor for stone formation in the lower calix, probably because it creates abnormal urodynamic and morphological features, especially when accompanied by other metabolic abnormalities.