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Accurate measurement of testicular volume (TV) in boys is an important tool in clinical practice, e.g., in varicocele treatment. This study aims to assess the degree of intra- and interobserver variability of testicular volume measurements. In a prospective study, boys between 11 and 17 years of age without testicular pathology were enrolled. Testicular ultrasound was performed by three investigators (A: pediatric radiologist; B: pediatric surgery/urology resident; C: pediatric urologist). Intraobserver variability was calculated in investigators B and C and interobserver variability between all three investigators. A total of 30 boys were enrolled. Mean intraobserver variability in both observers was +0.3% with a range of -39.6 to 51.5%. The proportion of measurements with a difference >20% was 18.6%. The mean interobserver variability was -1.0% (range: -74.1% to 62.8%). The overall proportion of measurements with a difference >20% was 35%. A lower testicular size of < 4 mL showed a significantly higher rate of >20% difference in both the intraobserver group (31.1% vs. 14.4%; p = 0.035) and the interobserver group (63.2% vs. 26.2%; p = 0.000031). Furthermore, the rate of >20% difference was significantly lower in obese compared to non-obese patients in both the intraobserver (2.8% vs. 22.4%; p = 0.0084) and the interobserver group (24% vs. 40.8%, p = 0.0427). Both intraobserver and interobserver variability in ultrasound-based TV measurements in pubertal boys contain a relevant degree of uncertainty that renders them unsuitable for individualized follow-up care. At the cohort level, however, mean differences in ultrasound-based TV measurements are low enough to make ultrasound comparisons reasonable.
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PURPOSE: Isolated fallopian tube torsion (IFTT) is defined by rotation of the fallopian tube around itself without involving the ipsilateral ovary. It is a rare cause of acute lower abdominal pain in (adolescent) girls, but is commonly overlooked. Due to its rarity, literature is still scarce. Currently there is no generally accepted management and treatment. METHODS: A retrospective analysis of all IFTT cases treated in our institution was performed. In addition, a systematic literature research on pediatric IFTT was carried out on Medline/ PubMed database according to PRISMA principles using predefined search terms and inclusion criteria. Patient characteristics regarding age, clinical symptoms, diagnostic methods, treatment, and follow-up were analyzed. RESULTS: Three of our patients and fifty-nine reports totaling one hundred seventy girls were included in the analysis. Mean age was 13.0 years. Left tube was slightly more often affected (52.9%). Abdominal pain was present in 99.4% of cases accompanied with nausea in 57.1%. In only 16.4%, correct preoperative diagnosis was made. Salpingectomy was the most common treatment in 111 (66.9%) cases, 55 (33.1%) patients were treated with detorsion of the tube (organ-sparing management). Girls with symptoms longer than 1 day had a significant higher rate of salpingectomy (95% CI, P = 0.0323). CONCLUSION: When IFTT is suspected, emergency laparoscopy should be performed to possibly preserve future reproductive potential. In case of detorsion and reinstated blood supply, organ-preserving management should be performed with simultaneous addressment of concomitant pathology if possible. Sufficient long-term follow-up must be assured to get significant results to introduce guidelines for children and adolescents.
Subject(s)
Fallopian Tube Diseases , Torsion Abnormality , Humans , Female , Adolescent , Child , Torsion Abnormality/surgery , Torsion Abnormality/diagnosis , Fallopian Tube Diseases/surgery , Fallopian Tube Diseases/complications , Fallopian Tube Diseases/diagnosis , Retrospective Studies , Abdominal Pain/etiology , Salpingectomy/methods , Fallopian Tubes/surgery , Laparoscopy/methodsABSTRACT
Anorectal malformations (ARM) represent a spectrum of rare malformations originating from a perturbated development of the embryonic hindgut. Approximately 60% occur as a part of a defined genetic syndrome or within the spectrum of additional congenital anomalies. Rare copy number variations (CNVs) have been associated with both syndromic and non-syndromic forms. The present study represents the largest study to date to explore the contribution of CNVs to the expression of ARMs. SNP-array-based molecular karyotyping was applied in 450 individuals with ARM and 4392 healthy controls. CNVs were identified from raw intensity data using PennCNV. Overlapping CNVs between cases and controls were discarded. Remaining CNVs were filtered using a stringent filter algorithm of nine filter steps. Prioritized CNVs were confirmed using qPCR. Filtering prioritized and qPCR confirmed four microscopic chromosomal anomalies and nine submicroscopic CNVs comprising seven microdeletions (del2p13.2, del4p16.2, del7q31.33, del9p24.1, del16q12.1, del18q32, del22q11.21) and two microduplications (dup2p13.2, dup17q12) in 14 individuals (12 singletons and one affected sib-pair). Within these CNVs, based on their embryonic expression data and function, we suggest FOXK2, LPP, and SALL3 as putative candidate genes. Overall, our CNV analysis identified putative microscopic and submicroscopic chromosomal rearrangements in 3% of cases. Functional characterization and re-sequencing of suggested candidate genes is warranted.
Subject(s)
Anorectal Malformations , DNA Copy Number Variations , Humans , Anorectal Malformations/genetics , Chromosome Aberrations , KaryotypingABSTRACT
Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.
Subject(s)
Bladder Exstrophy , Urinary Bladder Neoplasms , Humans , Animals , Mice , Bladder Exstrophy/genetics , Bladder Exstrophy/complications , Genome-Wide Association Study , Urinary Bladder Neoplasms/genetics , Transcriptome , Ephrin-A1/geneticsABSTRACT
BACKGROUND: The nutcracker syndrome (NCS) is defined by compression of the left renal vein (LVR) and may present with a wide variety of symptoms. Due to its rarity in pediatric patients, incidence, diagnostics and performed therapy regimen are widely undefined. To this date, there are only case reports and small collectives of pediatric patients described but comprehensive research is lacking. METHODS: A systematic literature research on pediatric NCS was carried out on Medline and Scopus databases according to PRISMA principles using predefined search terms and inclusion criteria. The PROSPERO registered review (CRD42021237415) identified patients' characteristics regarding age, sex, clinical symptoms, applied diagnostic methods and treatment options. RESULTS: In total 47 articles were included. Overall, 423 children (218 boys and 205 girls) with diagnosed NCS were included in the analysis. Mean age was 12.0 (boys 12.9, girls 12.0) years. Hematuria was most common presentation (55.5%), followed by proteinuria (49.9%). Classical flank pain was only detected in 19.1% of patients. Sonographic evaluation was the most commonly used diagnostic tool (99%). Invasive diagnostic studies were performed in 97 children. 86.8% patients were treated conservatively and 94.9% showed complete resolution (42.8%) or at least improvement (52.2%) of symptoms. Type of operative treatment comprised of open surgery with transposition of LRV, endovascular stenting and laparoscopy. CONCLUSIONS: Overall, data quality regarding NCS in children is poor. However, conservative approach in pediatric patients is recommended and should be regarded first treatment option. Diagnostic and treatment should follow a defined algorithm when NCS is suspected. Sufficient observation and follow-up must be assured in all patients to get significant results in this heterogenous syndrome. LEVEL OF EVIDENCE: V-IV.
Subject(s)
Renal Nutcracker Syndrome , Child , Female , Hematuria/etiology , Humans , Male , Renal Nutcracker Syndrome/diagnosis , Renal Nutcracker Syndrome/surgery , Renal Veins/surgeryABSTRACT
Introduction: Since early 2020 the COVID-19 pandemic and statutory preventive reorganization of treatment capacities with cancellation of elective surgery as well as curfew regulations led to vastly decreased utilization of primary health care. Materials and Methods: To assess whether there are negative effects on pediatric acute care in Bavaria during the spring 2020 lockdown a state-wide retrospective multi-center study was performed to analyze the rate of perforated appendicitis during lockdown. Children who have been operated on during the corresponding period in 2018/19 served as control group. Results: Overall, 514 patients (292 boys, 222 girls) were included (2020: 176 patients; 2019: 181 patients; 2018: 157 patients). Median age was 11.2 years. Four hundred thirty-nine patients (85.4%) underwent laparoscopic surgery, 69 (13.4%) open surgery and 1.2% underwent conversion from laparoscopic to open surgery. In 2020 a perforation rate of 27.8% (49/176 patients) was found, in 2018-2019 perforation rate was 20.7% (70/338 patients, p = 0.0359, Cochran-Mantel-Haenszel-Test). Subgroup analysis showed that in younger patients (≤ 11.2 years), in 2020 perforation rate was significantly higher with 37.6% (32/85 patients), while 22.2% (39/176) in 2018/2019 (p = 0.014, Fisher's exact test).In boys perforation rate was significantly higher in 2020 with 35.0% (35/100 patients) compared to 21.4% in 2018-2019 (p = 0.0165, Fisher's exact test). Conclusion: During the period of curfew regulations in Bavaria the rate of perforated appendicitis in childhood increased significantly, especially in younger children and boys. Potentially this has to be attributed to delayed presentation to pediatric surgery care. Because of potential long-term sequelae of perforated appendicitis these adverse effects during curfew have to be taken into account for future political decision making to ensure reasonable patient care and avoid collateral damage in near-future or on-going pandemic situations.
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BACKGROUND: For the Y-subtype of urethral duplications expression and nomenclature vary, as treatment recommendations do. OBJECTIVE: To raise awareness of the variety and variable terminology of Y-type duplication of the urethra, and to discuss the diagnostic work-up in light of options for or against surgical reconstruction. MATERIALS AND METHODS: Five patients with congenital Y-urethra were treated in four institutions within 15 years (2004-2019). While patients were managed in our respective institution with some exchange of experience, all available data were shared and evaluated for this review. RESULTS: The age at initial presentation was 1 day-6 months. In three patients the Y-urethra was found together with an anorectal malformation (ARM). With the focus on reconstruction rather than suprapubic diversion the orthotopic urethra was restored in the majority of patients using either single-step or staged approaches while the accessory urethral limb was incorporated. This was successful despite additional procedures aiming at ARM reconstruction. The patients void spontaneously and do control urine and bowels. One patient underwent kidney transplantation as a consequence of associated renal anomalies while reconstructive attempts regarding his urethral anomaly failed. In two patients, uncertainty in recognizing the pathology delayed a purposive treatment. DISCUSSION: For this rare anomaly the terminology in the literature merges and suggestions for the treatment differ. Success in four out five patients supports an approach which makes use of the accessory ventral track to restore the orthotopic urethra. Since some patients present as a neonatal emergency with concomitant problems such as ARM, a basic understanding of the variable pathology is required. CONCLUSION: The cases of Y-urethra reported herein demonstrate that correct allocation at the initial presentation or at least prior to first surgical steps will preserve the chance for physiologic micturition and urinary continence. Timing of surgery has to be done in the context of associated malformations and is not an emergency as long as proper bladder drainage is ensured. However, relocation of the accessory track requires several procedures bearing risks of complications short and long-term. This may be an argument to consider any therapeutic strategy against other options such as postponed treatment or permanent suprapubic diversion. Evidence-based guidelines are lacking.
Subject(s)
Anorectal Malformations , Kidney Diseases , Urethral Diseases , Humans , Infant, Newborn , Male , Urethra/surgery , Urethral Diseases/diagnosis , Urethral Diseases/surgery , UrinationABSTRACT
BACKGROUND: Acute urinary retention is a common emergency in adult patients, foremost in older men. In childhood urinary retention is a rare entity with only sparse literature on the etiology. OBJECTIVE: To assess the etiology and treatment of acute urinary retention in the pediatric population and assess age and sex distribution. STUDY DESIGN: A retrospective analysis of all patients admitted to our emergency department with acute urinary retention between 2005 and 2019 was performed. Exclusion criteria were newborns (because of physiologic postnatal oliguria) and postoperative urinary retention during the same hospital stay. RESULTS: 113 children with acute urinary retention (ICD: R33) meeting the above criteria were identified. 16 Patients were excluded because of incomplete medical charts. 97 children were included into the study (age 0.5-18.3 years, mean age 5.3 years). 89 patients had one episode, 8 patients two episodes. A peak around the third year of age was observed. Sex ratio showed a 2:1 male to female distribution. Most common etiology was balanoposthitis (15.5%) and acute constipation/fecal impaction (15.5%). Traumatic urinary retention was found in 11.4% of the cases. Urinary tract infection were found 7.2%. No underlying reason could be found in 12.4% (idiopathic urinary retention). Other causes included febrile non-urinary infection (8.2%), subvesical obstruction (4.1%), vulvovaginitis (3.1%) and urethritis (2.1%). In 50% of the cases of urinary retention under 1 year of age (2 out of 4) an underlying tumor (rhabdomyosarcoma, sacral teratoma) was identified. DISCUSSION: Age and sex distribution were similar to previously published series; however, this study shows a marked difference concerning the etiology: e. g. we identified a significantly higher proportion of functional disorders as a reason for acute urinary retention in childhood. It is hypothesized that this is partly because previously published studies originate from areas (USA, Israel, Iran) with different socio-demographic and cultural background. CONCLUSION: AUR in children is a rare condition with very heterogeneous causes. Although the majority of cases exhibit mild underlying conditions, serious reasons, such as malignant diseases especially in the first year of life, must be excluded. AUR relief without catheterization is a child-friendly approach in cases of mild inflammatory or functional disorders and can help to minimize traumatization.
Subject(s)
Urinary Retention , Urinary Tract Infections , Acute Disease , Adolescent , Aged , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Iran , Israel , Male , Retrospective Studies , Urinary Retention/diagnosis , Urinary Retention/epidemiology , Urinary Retention/etiologyABSTRACT
The term "megaureter" is an entirely descriptive designation for a number of different entities. It is crucial to distinguish between primary and secondary forms of megaureter and between obstructive and/or refluxive forms. In the majority of cases, there is a primary obstruction in the terminal ureterovesical segment. The treatment of primary obstructive megaureter has changed fundamentally over the last 3 decades. Whereas ureteral reimplantation was the treatment of choice in the past, conservative treatment is now preferred in 85 to 90â% of patients. With the advent of endoscopic balloon dilatation, a modern, minimally-invasive treatment option has become an alternative to ureteral reimplantation in selected patients. However, due to the possibility of postoperative VUR (vesicoureteral reflux), it is necessary to emphasize that this option should not weaken the generally strict indication for surgical treatment of primary obstructive megaureter.
Subject(s)
Conservative Treatment , Ureteral Obstruction/therapy , Endoscopy , Humans , Postoperative Complications , Ureter/physiopathology , Ureter/surgery , Ureteral Obstruction/physiopathology , Vesico-Ureteral RefluxABSTRACT
Tissue engineering is defined as the combination of biomaterials and bioengineering principles together with cell transplantation or directed growth of host cells to develop a biological replacement tissue or organ that can be a substitute for normal tissue both in structure and function. Despite early promising preclinical studies, clinical translation of tissue engineering in pediatric urology into humans has been unsuccessful both for cell-seeded and acellular scaffolds. This can be ascribed to various factors, including the use of only non-diseased models that inaccurately describe the structural and functional modifications of diseased tissue. The paper addresses potential future strategies to overcome the limitations experienced in clinical applications so far. This includes the use of stem cells of various origins (mesenchymal stem cells, hematopoietic stem/progenitor cells, urine-derived stem cells, and progenitor cells of the urothelium) as well as the need for a deeper understanding of signaling pathways and directing tissue ingrowth and differentiation through the concept of dynamic reciprocity. The development of smart scaffolds that release trophic factors in a set and timely manner will probably improve regeneration. Modulation of innate immune response as a major contributor to tissue regeneration outcome is also addressed. It is unlikely that only one of these strategies alone will lead to clinically applicable tissue engineering strategies in pediatric urology. In the meanwhile, the fundamental new insights into regenerative processes already obtained in the attempts of tissue engineering of the lower urogenital tract remain our greatest gain.
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In a 10-yr-old boy with no abnormalities or symptoms other than nonretractability of the foreskin, the foreskin should be preserved. If treatment is needed, local corticoid application should be used as first-line therapy, as it gives excellent results in up to 90% of cases, before removing this sensitive part of the body.
Subject(s)
Circumcision, Male , Penile Neoplasms/epidemiology , Phimosis/complications , Phimosis/surgery , Child , Circumcision, Male/adverse effects , Communication , Humans , Male , Parents/education , Puberty , Remission, Spontaneous , Sexually Transmitted Diseases/epidemiology , Urinary Tract Infections/epidemiology , Urinary Tract Infections/prevention & controlABSTRACT
Epididymitis is one of the most frequent causes of acute scrotum during childhood. Unlike in adults, ascending bacterial infections are rarely the underlying cause of the condition in children. Antibacterial treatment in accordance with a prior antibiogram is possible in the presence of leukocyturia and significant bacteriuria. For the remaining cases, there are no definite criteria allowing for a decision on acute antibacterial treatment. The fact that antibacterial treatment is still initiated in cases of epididymitis in the clinical routine setting is based on the assumption of a possible infection rather than being based on facts. This dilemma will probably not be entirely resolved until adequate diagnostic markers for the different trigger mechanisms of epididymitis have been found.
Subject(s)
Epididymitis , Acute Disease , Child , Diagnosis, Differential , Epididymitis/diagnosis , Epididymitis/physiopathology , Epididymitis/therapy , Humans , Male , ScrotumABSTRACT
Gardner fibromas (GFs) have only recently been described as poorly circumscribed tumor-like lesions, which are exceedingly rare in children. GFs are associated with APC gene mutations and therefore with familial adenomatous polyposis (FAP). So far there is only very limited literature on GF in the neonatal period. We present two children with GF diagnosed at birth and subsequent FAP with very different clinical courses. In one case, the disease led to extensive surgery of the thoracic wall and detection of FAP in the father with the need of immediate proctocolectomy. In the other patient (with a positive family history for FAP) the disease remained stable. Our cases indicate that the diagnosis of GF in the neonatal period requires the exclusion of FAP both in the child as well as the parents. Since the clinical behavior of GF cannot be predicted, continuous monitoring is mandatory. Depending on tumor site and growth, individual therapeutic options must be thoroughly considered. Surgical resection, if necessary, has to be inevitably total to prevent recurrence.
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PURPOSE: Bladder outlet obstruction is a finding in many urological disorders, leading to bladder wall hyperplasia. We investigated platelet derived growth factor and its receptor in human bladder smooth muscle cells and urothelial cells exposed to hydrostatic pressure or PDGF in vitro. MATERIALS AND METHODS: Bladder smooth muscle cells and urothelial cells were exposed to elevated hydrostatic pressure for 1 hour. The expression of PDGF and PDGFR was evaluated using reverse transcriptase-polymerase chain reaction and Western blot analysis. Pressure or PDGF induced proliferation of bladder smooth muscle cells with or without pretreatment with lovastatin or imatinib was measured by enzyme-linked immunosorbent assay. PDGFRα was knocked down with siRNA. RESULTS: After hydrostatic pressure bladder smooth muscle cells showed increased PDGFRα and ß expression. PDGF was not expressed in bladder smooth muscle cells. Urothelial cells showed no expression of PDGFR but PDGF expression was noted. Western blot analysis of bladder smooth muscle cells revealed a pressure induced increase in PDGFR in the membrane fraction. Phosphorylation of PDGFR occurred with pressure induction. Bladder smooth muscle cell proliferation was increased in pressure and PDGF mediated fashion. Pretreatment with lovastatin or imatinib prevented proliferation. There was no cell proliferation after PDGFRα knockdown. CONCLUSIONS: Increased expression and phosphorylation of PDGFR in bladder smooth muscle cells after hydrostatic pressure suggests a pivotal role of the PDGF pathway in pressure induced hyperplasia of bladder smooth muscle cells. PDGF expressed in urothelial cells may act in a paracrine way. Cholesterol depletion, inhibition of receptor tyrosine kinase activity and knockdown of PDGFRα in bladder smooth muscle cells prevent pressure and PDGF mediated cell proliferation. Targeting PDGFR seems a promising way to influence pressure induced bladder wall hyperplasia.
Subject(s)
Muscle, Smooth/pathology , Paracrine Communication/physiology , Platelet-Derived Growth Factor/physiology , Urinary Bladder/pathology , Urodynamics/physiology , Blotting, Western , Cell Proliferation/drug effects , Cell Proliferation/genetics , Cell Proliferation/physiology , Child , Gene Knockdown Techniques , Humans , Hydrostatic Pressure , Hyperplasia , Imatinib Mesylate/pharmacology , In Vitro Techniques , Lovastatin/pharmacology , Muscle, Smooth/drug effects , Paracrine Communication/drug effects , Paracrine Communication/genetics , Phosphorylation/physiology , Real-Time Polymerase Chain Reaction , Receptor, Platelet-Derived Growth Factor alpha/drug effects , Receptor, Platelet-Derived Growth Factor alpha/genetics , Receptor, Platelet-Derived Growth Factor alpha/physiology , Urinary Bladder/drug effects , Urinary Bladder Neck Obstruction/genetics , Urinary Bladder Neck Obstruction/pathology , Urinary Bladder Neck Obstruction/physiopathologyABSTRACT
PURPOSE: The option of nephron sparing surgery for unilateral Wilms tumor has been debated in the recent literature. This procedure is being used increasingly to preserve kidney tissue and function. However, nephron sparing surgery is feasible only for selected cases, and a higher local relapse rate has been observed. Moreover, a significant reduction of nephrons is associated with development of renal hypertension and progressive renal failure. We analyzed outcomes after bilateral partial nephrectomy and unilateral partial plus contralateral total nephrectomy in patients with bilateral Wilms tumor. MATERIALS AND METHODS: We analyzed data from the Society of Pediatric Oncology and Hematology database on 22 patients with bilateral Wilms tumor. Kidney size was measured using volumetric analysis of magnetic resonance imaging. Patients were matched with children who had undergone magnetic resonance imaging of the abdomen for other malignancies. RESULTS: Mean kidney volumes after unilateral partial plus total contralateral nephrectomy (66.9 cm(3)) were significantly greater than the reference kidneys (p = 0.028), whereas controls were equal to the bilateral partial nephrectomy group (49.7 cm(3), p = 0.959). Total kidney volume was significantly larger after bilateral partial nephrectomy (102.1 cm(3)) vs unilateral partial plus total contralateral nephrectomy (66.9 cm(3), p = 0.0338). Eight patients (66.7%) had renal hypertension after unilateral partial plus total contralateral nephrectomy but only 2 (20%) after bilateral partial nephrectomy (p = 0.043). Overall survival and relapse rates were equal between the groups and did not correlate with unfavorable histology. CONCLUSIONS: Our findings suggest that patients with bilateral Wilms tumor benefit from bilateral nephron sparing surgery. Hypertension is less common after bilateral partial nephrectomy, and rates of local relapse or disease associated death are distributed equally between the groups.
Subject(s)
Hypertension/prevention & control , Kidney Neoplasms/surgery , Nephrectomy/methods , Organ Sparing Treatments , Postoperative Complications/prevention & control , Wilms Tumor/surgery , Humans , Nephrons , Retrospective StudiesABSTRACT
The Wilms tumor 1 (WT1) gene plays an essential role in early development and differentiation of the urinary tract, particularly the kidneys. Aberrant transcriptional activity of WT1 is a key finding in the genesis of Wilms tumors (WTs). However, the mechanisms responsible for this alteration remain poorly understood. In the present study, we examined the methylation pattern of a putative CCCTC-binding factor (CTCF) binding site downstream of the WT1 gene as a potential cause of WT1 misregulation in 44 native WT specimens. We found that 16 WT cases exhibited a much higher WT1 expression compared to normal kidney tissue, and that the high mRNA expression of WT1 is strongly correlated with a high degree of DNA methylation of the CTCF binding site near the WT1 promoter. However, there was no correlation between the KTS+/KTS- splicing variants of WT1 and the methylation status of the CpGs of the CTCF binding site. Our results demonstrated an aberrant methylation pattern at a CTCF binding site downstream the WT1 gene, which is associated with an elevated WT1 transcriptional activity. Thus, methylation of the CTCF binding site may be partially responsible for the transcriptional activation of the WT1 locus and hypermethylation of this site may be an important oncogenic mechanism in the genesis of WT.