Interstitial Cells of Cajal and P2X3 Receptors at Ureteropelvic Junction Obstruction and Their Relationship with Pain Response.

Introduction: Etiopathogenesis and the symptomatology of ureteropelvic junction obstruction (UPJO) in the pediatric population has not yet been definitely clarified, suggesting a multifactorial nature of the condition. The aim was to analyze the association between the number of Interstitial Cells of Cajal (ICCs), as well as P2X3 receptors in ureteropelvic junction (UPJ) and the pain response in pediatric patients with hydronephrosis. Methods: 50 patients with congenital hydronephrosis underwent open or laparoscopic pyeloplasty at one of two departments of pediatric surgery and urology in Poland. Patients were divided into two groups according to the pain symptoms before surgery. A total of 50 samples of UPJ were obtained intraoperatively and underwent histopathological and immunohistochemical (IHC) analysis. Quantitative assessment of ICCs was based on the number of CD117(+) cells of adequate morphology in the subepithelial layer and the muscularis propria. Expression of P2X3 receptors was evaluated as the intensity of IHC staining. Results: Patients with hydronephrosis and accompanying pain were on average 60 months older (77 vs. 17 months) than children with asymptomatic hydronephrosis (p = 0.017). Symptomatic children revealed higher numbers of ICCs in both the subepithelial layer and in the lamina muscularis propria. In particular, symptomatic patients aged 2 years or more exhibited significantly higher numbers of ICCs in the subepithelial layer. Significant differences in the distribution of ICCs between the subepithelial layer and the lamina muscularis propria were observed in both groups. Expression of P2X3 receptors was limited to the urothelium and the muscle layer and correlated between these structures. There was no relationship between pain response and the expression of P2X3 receptors. Conclusions: ICCs and P2X3 receptors may participate in the pathogenesis of UPJO and in the modulation of pain response to a dilatation of the pyelocaliceal system. Explanation of the role of ICCs and P2X3 receptors in propagation of ureteral peristaltic wave and the modulation of pain stimuli requires further studies.

Genome-Wide Survey for Microdeletions or -Duplications in 155 Patients with Lower Urinary Tract Obstructions (LUTO).

Lower urinary tract obstruction (LUTO) is, in most cases, caused by anatomical blockage of the bladder outlet. The most common form are posterior urethral valves (PUVs), a male-limited phenotype. Here, we surveyed the genome of 155 LUTO patients to identify disease-causing CNVs. Raw intensity data were collected for CNVs detected in LUTO patients and 4.392 healthy controls using CNVPartition, QuantiSNP and PennCNV. Overlapping CNVs between patients and controls were discarded. Additional filtering implicated CNV frequency in the database of genomic variants, gene content and final visual inspection detecting 37 ultra-rare CNVs. After, prioritization qPCR analysis confirmed 3 microduplications, all detected in PUV patients. One microduplication (5q23.2) occurred de novo in the two remaining microduplications found on chromosome 1p36.21 and 10q23.31. Parental DNA was not available for segregation analysis. All three duplications comprised 11 coding genes: four human specific lncRNA and one microRNA. Three coding genes (FBLIM1, SLC16A12, SNCAIP) and the microRNA MIR107 have previously been shown to be expressed in the developing urinary tract of mouse embryos. We propose that duplications, rare or de novo, contribute to PUV formation, a male-limited phenotype.

Laparoscopic versus open pyeloplasty in children: experience of 226 cases at one centre.

INTRODUCTION: The aim of the study was to compare the efficacy of laparoscopic versus open dismembered pyeloplasty in children. MATERIAL AND METHODS: Two hundred and twenty-six Anderson-Hynes pyeloplasties were performed, out of which 131 by open access (OP) and 95 by laparoscopic access (LP). Retrospective analysis of data was performed. The median follow-up was 3 years for LP patients and 6 years for OP patients (p < 0.05). RESULTS: Success was achieved in 87 (91.57%) patients who had LP surgeries and in 121 (91.7%) patients who had OP (p > 0.05). Eight patients in the LP group and nine in the OP group required another surgery because of recurrent UPJO, and one patient in the OP group required a nephrectomy. The median operating time was 125 min (range: 70-225) for LP surgeries and 90 (40-200) for OP surgeries (p < 0.05). In the last 30 LP procedures, operation time decreased to a median of 95 min. Improvement in ultrasound analysis of the kidney was achieved in 89.06% of patients who had LP and 82.35% of patients who had OP. A stable or better function of the kidney in diuretic renography was achieved in 87.5% of patients in the LP group and 96.15% of patients in the OP group. CONCLUSIONS: Laparoscopic and open pyeloplasty is a highly efficient procedure employed to treat UPJO in children with comparable success rates in both groups. In experienced hands, it is possible to reduce the LP operation time to that comparable to the OP group.

Detection rate of crossing vessels in pediatric hydronephrosis: Transperitoneal laparoscopy versus open lumbotomy.

BACKGROUND: A bundle of crossing vessels (CV) supplying the lower pole of the kidney and causing mechanical obstruction of the ureteropelvic junction (UPJ) has been the subject of many discussions. During pyeloplasty, it is possible to overlook the CV. This may result in recurrent dilatation of the kidney and the need for re-surgery. OBJECTIVES: To compare the detection rate of CV in UPJ obstruction (UPJO) depending on the operational access applied (transperitoneal laparoscopy (LAP) vs open lumbotomy (OPEN)). Assessment of features that could indicate the presence of CV. MATERIAL AND METHODS: Two hundred and forty-six pediatric pyeloplasties were performed between January 2006 and July 2017 in the Department of Pediatric Surgery and Urology at the Wroclaw Medical University, Poland - 111 out of them by LAP and 135 by OPEN, on 98 girls and 148 boys. A retrospective analysis of the patient records for the detection of CV and characteristics of the CV before surgery was performed. RESULTS: Intraoperative CV causing obstruction of the UPJ in the LAP group were recognized in 34.2% (n = 38) of the patients, and within the OPEN group in 12.5% (n = 17) (p < 0.0001); 90% (n = 27) of patients with the diagnosed CV did not show congenital hydronephrosis. In 68% (n = 21) of the patients there were cases of recurrent renal colic. The presence of CV was suspected in 7.2% of kidney ultrasounds and in 12.5% in computed tomography (CT) urograms. CONCLUSIONS: The detection rate of CV in UPJO is statistically higher in LAP access than in open retroperitoneal lumbotomy. The distinguishing features of patients with CV are the lack of prenatal diagnosis for hydronephrosis and the presence of pain in the lumbar region.

Hydronephrosis in Children Caused by Lower Pole Crossing Vessels-How to Choose the Proper Method of Treatment?

Objectives: Assessment of the efficacy of intraoperative diagnosis between extrinsic and intrinsic UPJO in children. Assessment of the efficacy of laparoscopic vascular-hitch procedure in UPJO caused by lower pole crossing vessels (CV). Materials and Methods: Between 2008 and 2017, 47 laparoscopic procedures were performed with the CV discovered intraoperatively. CV were translocated cephalad, and the UPJ was carefully inspected. The Chapman's vascular hitch procedure was accomplished in the case of decreasing sizes of the pelvis and clear, visible peristalsis of the UPJ (31 patients). In the other cases, Anderson-Hynes (A-H) pyeloplasty with posterior translocation of the CV was performed (16 patients). Results: The median age at operation was 6 years (range 1-16) in VH and 6 years (range 2-17) in A-H (p = 0.4635). Prenatal dilatation of kidney was diagnosed in 18.7% of VH and 10% of A-H cases (p = 0.5474). Success was achieved in 16 (100%) patients in the A-H and in 29 (93.54%) in the VH groups. Two patients (6.5%) in VH required repeated surgery because of a misdiagnosed intrinsic obstruction. Median operation time in VH was 80 min (range 40-105) and was 105 (range 70-225) in A-H (p < 0.05). Conclusions: The intraoperative selection based on intraoperative pelvis and UPJ appearance after vessel transposition is sufficient in majority of cases. Laparoscopic vascular hitch seems to be effective and safe procedure, but can only be performed on carefully selected patients. In case of misdiagnosis, reoperation is possible with the same laparoscopic access.

Laparoscopic Heminephrectomy for Duplex Kidney in Children-The Learning Curve.

Objectives: Outcomes evolution during the learning curve of laparoscopic transperitoneal heminephrectomy in children with a duplex kidney. Materials and Methods: The data of 33 children, operated on between 2008 and 2017, with complicated duplex kidney, were subjected to a retrospective analysis. All patients were operated on by transperitoneal access using the laparoscopic technique. Patients were divided into two groups (1: subsequent operation 1-16, and 2: operations 17-33) to evaluate the learning curve. Results: There was no need for conversion. Total complications occurred in seven patients in Group 1 and 2 patients of Group 2 (p < 0.05). Two patients (6%) (both upper pole heminephrectomies) required reoperation to remove the ureter stump because of recurrent UTIs due to undiagnosed VUR to the stump (1 from each of Groups 1 and 2). Prolonged urine leakage (over 4 days) was observed in four patients (12%; all from group 1); in three patients, conservative treatment was successful, while the placement of a DJ catheter was needed in the fourth. A significant decrease of kidney function (>6%) in scintigraphy was observed in two of the 15 patients after the surgery. The time of surgery decreased from 140 (range 85-185) min in Group 1 to 125 (range 100-150) min in Group 2 (p < 0.05). Conclusions: Laparoscopic heminephrectomy is connected to the learning curve. Most complications occurred in the first 16 operations. With increasing experience, the time of operation decreased. In patients with reflux to the upper pole, referred for upper pole heminephrectomy, it is necessary to consider the removal of the ureter to the level of the vesicoureteral junction.

Anderson-Hynes pyeloplasty in children - long-term outcomes, how long follow up is necessary?

INTRODUCTION: Pyeloplasty is commonly conducted in children with uretero-pelvic junction obstruction. Standard post-operational procedure involves only a short period of time after the surgery. What is the real number of complications, including those in the long-term? What is the function of the operated kidney?The aims of this study are to assess the effectiveness of pyeloplasty and to assess the suitability of conducting long term follow-up after pyeloplasty. MATERIAL AND METHODS: 35 of 137 patients after open pyeloplasty between 1992-2006 responded to the invitation and returned for a control appointment. The median age was 8 years (range 1 month - 19 years). In 26 kidney units the disease proceeded with symptoms and in 10 cases it proceeded without symptoms. The predominant symptom was abdominal pain (n = 21). In each child both the control ultrasound and the diuretic renal scintigraphy of the kidneys were conducted. RESULTS: Regression of symptoms after the operation was obtained in 19 kidney units (73%). Improvement in scintigraphy was observed in 23 kidney units (82.1%), improvement in ultrasound was obtained in 32 (91%) kidney units. Complications which required surgical intervention occurred in 4 (11.1%) patients. One patient required operative removal of a pyelostomy tube, 2 patients (11.1%) required repeated pyleoplasty (23 and 27 months after the operation), one child required nephrectomy due to nephrogenic arterial hypertension (after 4 years). CONCLUSIONS: Statistically, there are improvements of scintigraphic function of the kidney, improvements in ultrasound examinations, and the remission of symptoms after pyeoplasty. Most complications occur within 2 years after the surgery. Long-term follow up should be continued.

Transurethral Resection of the Bladder Tumour as a Treatment Method in Children with Transitional Cell Carcinoma of the Bladder--Analysis of Our Material and Literature Review.

BACKGROUND: Bladder cancer occurs mainly in adults. In children, younger than 10 years in particular, it is very rare. OBJECTIVES: The aim of the study is to retrospectively evaluate the efficacy of transurethral resection of the bladder tumour (TUR-BT) of transitional cell carcinoma (TCC) of the bladder in children. MATERIAL AND METHODS: Transurethral resection of the bladder tumour was performed in 7 boys aged 4 to 17 years (median 12.1 years). In all cases laboratory tests, ultrasound, and cystoscopic tumour biopsy were carried out prior to the resection. Doxorubicin was additionally instilled intravesically as one dose in two patients. The Foley catheter was left in the bladder for 1 to 4 days (median 1.85 days). The follow-up period ranged from 10 months to 10 years (median 4 years). RESULTS: Papillary urothelial neoplasm of low malignant potential (PUNLMP) was diagnosed in 5 patients and urothelial papilloma in 2. Local recurrence was observed in one case two years after the resection. In all other cases complete remission was achieved. CONCLUSIONS: Transitional cell carcinoma of the bladder in children is usually benign and endoscopic treatment (TUR-BT) seems to be the treatment of choice. To determine a follow-up schedule a more substantial group of children with bladder cancer should be analysed.

Interferon alpha and metronomic cyclophosphamide for metastatic kidney cancer: a phase 2 study.

Metronomic chemotherapy has been tested only a few times in the treatment of metastatic kidney cancer. We have combined metronomically dosed cyclophosphamide (mCTX) with full dosed interferon alpha (IFN) in patients with disseminated clear cell cancer. Toxicity was mainly attributable to IFN treatment. We have noticed mainly hematological and general symptoms with only few grade 3 or 4 adverse events. No patient required mCTX withdrawal. In 30 patients evaluated for the response, clinical benefit (CB) (objective responses and stabilization of the disease ≥24 weeks) was observed in 40%. Median overall survival (OS) for the whole group was 13.2 months. Survival responders and nonresponders were 9.5 versus 28.9 months (P=0.001). Patients with a higher hemoglobin concentration and fibrinogen level <6 g/L had a higher probability of response. Responders also had different kinetics of fibrinogen than nonresponders. When assessed for clinical response, the combination of mCTX and IFN proved to be disappointing. In contrast, OS in patients with CBs proved to be long. It is crucial to properly select patients for whom some predictive markers can be used. The combination of metronomic chemotherapy with targeted therapies might be an interesting direction for further research.

An evaluation of the effectiveness of external urethral meatus incision in girls with an anterior deflected urinary stream and symptoms of detrusor overactivity.

BACKGROUND: Urethral stenosis or abnormalities in the external urethral meatus in girls may lead to serious functional bladder outlet obstruction and recurrent urinary tract infections. OBJECTIVES: The aim of the study was to analyze the efficacy of meatotomy in girls with an anterior deflected urinary stream (ADUS) and symptoms of detrusor overactivity. MATERIAL AND METHODS: A group of 67 girls between the ages of 5 and 16 (mean age: 8.6 years) with symptoms of detrusor overactivity participated in the study. The girls were treated with oxybutinin in the years 2010-2011. The group included 37 girls with ADUS (the ADUS group) while the remaining 30 girls (the OXY group) were found to have a normal urinary stream. In the ADUS group an external urethral meatus incision was performed. The follow-up period was three months. The presence of urinary tract infections (UTI) as well as nocturnal bedwetting and daytime incontinence were analyzed before and after treatment. RESULTS: After three months, in the ADUS group no UTI was found in 12 children (32%) (p < 0.05), including 11 patients with prior febrile UTI (p < 0.05). Recovery from daytime urinary incontinence was observed in 20 girls (54%) and recovery from nocturnal bedwetting in 8 girls (22%). In the OXY group no infections were found in three girls (10%); recovery from daytime urinary incontinence was noted in 21 girls (70%) and from nocturnal bedwetting in 10 girls (33%). CONCLUSIONS: Girls with symptoms of detrusor overactivity accompanied by an anterior deflected urinary stream experience UTIs and fever more often than girls with detrusor overactivity and a normal urinary stream. An incision in the external urethral meatus in girls with ADUS and detrusor overactivity seems to be effective treatment for recurrent urinary tract infections, especially febrile ones.

Changes in interstitial cell of Cajal-like cells density in congenital ureteropelvic junction obstruction.

PURPOSE: The authors examined the number of interstitial cells of Cajal-like cells (ICC-LCs) in obstructed ureteropelvic junction (UPJ) in comparison with normal UPJ specimens and age-related changes. MATERIALS AND METHODS: A total of 20 human formalin fixed, paraffin-embedded specimens of intrinsic UPJO from children at the mean age of 8.1 years (age range: 8 months-16.8 years) and 5 control samples from children at the mean age of 2.3 years (range 2.4 months-7.4 years) were investigated immunohistochemically for the expression of c-kit proto-oncogene by light microscopy with computerized image analysis. The results were examined by Fisher's exact test, Yates' chi-square test, and t test for Pearson's correlation coefficient. A P value less than 0.05 was considered statistically significant. RESULTS: The number of ICC-LCs-dense fields was significantly higher in UPJO specimens in comparison with the normal group (P = 0.0004). The number of ICC-LCs-sparse fields was significantly lowered in UPJO specimens in comparison with the normal group (P = 0.0122). There was no significant difference in the number of ICC-LCs-medium fields in obstructed and normal UPJ specimens. The number of ICC-LCs was decreasing significantly with increasing age of the patients with UPJO (P = 0.0038). CONCLUSIONS: The higher density of c-kit-positive ICC-LCs in UPJ may manifest the compensation of altered peristalsis in UPJO. The number of ICC-LCs-dense fields decreasing with age may show the failure of compensation and regression of the compensatory changes.

Nondismembered pyeloplasty in a pediatric population: results of 34 open and laparoscopic procedures.

OBJECTIVE: To assess the outcomes of nondismembered pyeloplasty for ureteropelvic junction obstruction in a pediatric population of children and adolescents. METHODS: Between 2005 and 2009, a total of 129 pyeloplasties were performed at our institution. In all, 34 (24%) renal units underwent primary nondismembered Fenger-type plasty, 22 open (OPEN) and 12 laparoscopic (LAP). Gender distribution, left to right ratio, follow-up period, grade of kidney dilatation and split renal function were similar in both groups. The decision to perform a nondismembered procedure was made by the surgeon intraoperatively. The mean age at surgery was 4.5 years for the OPEN group and 14.2 years for the LAP group. Mean follow-up was 30 months (range 12-70 months). RESULTS: The overall success rate was 91% (95.5% the OPEN group and 83.5% in the LAP group). Secondary surgery was required for 3 renal units. Other complications included pyelonephritis in 3 patients (2 in OPEN and 1 in LAP), ileus in 1 patient (OPEN), and prolonged postoperative pain in 1 patient (LAP). The mean operation time was significantly shorter for open surgery (95 minutes for OPEN vs 179 minutes for LAP; P < .05). There was no significant difference in the length of the postoperative hospital stay (2.5 days for OPEN vs 3 days for LAP). CONCLUSION: Nondismembered pyeloplasty is an effective procedure for curing ureteropelvic junction obstruction in the pediatric population, and can be considered as an option in well selected cases.

Management of bladder neck leiomyoma during pregnancy.

A 29-year-old primigravida was admitted to the urology ward with acute urinary retention. The patient underwent cystoscopy, MRI (magnetic resonance imaging), and tissue biopsy, which consequently led to the diagnosis of bladder neck leiomyoma that obstructed urine outflow. Subsequent to a cesarean section, a successful transurethral resection was performed. Here the diagnostic complexity in the pregnant patient, clinical course, and outcome are described. One year after successful treatment both mother and daughter are in good condition.

Electrocoagulation versus clips in laparoscopic varicocelectomy in boys.

INTRODUCTION: Varicocele occurs in about 15% of adolescents, but it is hardly ever noticed in children under 10 years old. Surgical treatment in adolescents is still controversial. OBJECTIVES: The aim of this work was to assess the outcome of laparoscopic varicoelectomy by using electrocoagulation versus clips. MATERIALS AND METHODS: In the Pediatric Surgery and Urology Departments of the Medical University of Wroclaw, 139 boys with varicocele were operated on by using laparoscopy between 1995 and 2007. In total, 68 (49%) patients appeared for the control ultrasound after the surgery, and only those patients were included in this study. The spermatic vessels (both the artery and the vein) were trans-sected by monopolar diatermy (38 patients; 55.8%) or clips (29 patients; 42%). The spermatic Artery was saved in 5 cases, which have been operated on by using diatermy and in 3 by using clips. The follow-up was from 0.5 to 7 years (mean, 2.7 years). RESULTS: Among 68 patients from the control group of persistent varicocele with grade II and grade III (Dubin-Amelaar classification) were recognized in 5 (7.3%) boys. In the group of boys, who have been operated on by using diatermy, persistent varicocele was noticed in 10.5% (4), while in those who have been operated on by using clips, the persistent varicocele was recognized only in 3.4% (1). Varicocele with grade I, not demanding a second operation, was recognized in 9 boys (14.7%). The most often found complication was hydrocele. It was recognized in 23.7% (9) boys operated on by using diatermy and in 13.8% (4) boys operated on by using clips. CONCLUSIONS: Varicocelectomy using clips gives much less complications then the electrocoagulation and should be firstly chosen.