Mutations in microRNA processing genes in Wilms tumors derepress the IGF2 regulator PLAG1.

Many childhood Wilms tumors are driven by mutations in the microRNA biogenesis machinery, but the mechanism by which these mutations drive tumorigenesis is unknown. Here we show that the transcription factor pleomorphic adenoma gene 1 (PLAG1) is a microRNA target gene that is overexpressed in Wilms tumors with mutations in microRNA processing genes. Wilms tumors can also overexpress PLAG1 through copy number alterations, and PLAG1 expression correlates with prognosis in Wilms tumors. PLAG1 overexpression accelerates growth of Wilms tumor cells in vitro and induces neoplastic growth in the developing mouse kidney in vivo. In both settings, PLAG1 transactivates insulin-like growth factor 2 (IGF2), a key Wilms tumor oncogene, and drives mammalian target of rapamycin complex 1 (mTORC1) signaling. These data link microRNA impairment to the PLAG1-IGF2 pathway, providing new insight into the manner in which common Wilms tumor mutations drive disease pathogenesis.

How to improve initial diagnostic accuracy of kidney tumours in childhood?-A non-invasive approach.

Non-invasive differentiation of paediatric kidney tumours is particularly important in the SIOP-RTSG protocols, which recommend pre-operative chemotherapy without histological confirmation. The identification of clinical and tumour-related parameters may enhance diagnostic accuracy. Age, metastases, and tumour volume (TV) were retrospectively analysed in 3306 patients enrolled in SIOP/GPOH 9, 93-01, and 2001 including Wilms tumour (WT), congenital mesoblastic nephroma (CMN), clear cell sarcoma (CCSK), malignant rhabdoid tumour of the kidney (MRTK), and renal cell carcinoma (RCC). WT was diagnosed in 2927 (88.5%) patients followed by CMN 138 (4.2%), CCSK 126 (3.8%), MRTK 58 (1.8%) and RCC 57 (1.7%). CMN, the most common localized tumour (71.6%) in patients younger than 3 months of age, was diagnosed earliest and RCC the latest (median age [months]: 0 and 154, respectively) both associated with significantly smaller TV (median TV [mL]: 67.2 and 45.0, respectively). RCC occurred in >14% of patients older than 120 months or older than 84 months with TV <100 mL. Receiver operating characteristic analyses discriminated WT from CMN, RCC and MRTK regarding age (AUC = 0.976, 0.929 and 0.791) and TV (AUC = 0.768, 0.813 and 0.622). MRTK had the highest risk of metastasis (37.9%) despite young age, whereas the risk of metastasis increased significantly with age in WT. Age and TV at diagnosis can differentiate WT from CMN and RCC. MRTK must be considered for metastatic tumours at young age. Identification of CCSK without histology remains challenging. Combined with MRI-characteristics, including diffusion-weighted imaging, and radiomics and liquid biopsies in the future, our approach allows optimization of biopsy recommendations and prevention of misdiagnosis-based neoadjuvant treatment.

Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: A report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5.

BACKGROUND: Patients with stage IV favorable histology Wilms tumor (FHWT) with extrapulmonary metastases (EPM) constitute a small subset of patients with FHWT. Because of their rarity and heterogeneity, optimal FHWT treatment is not well understood. Children's Oncology Group protocol AREN0533 assigned patients with FHWT and EPM to intensified chemotherapy, regimen M, after initial DD-4A chemotherapy. To improve understanding of prognostic factors and best therapies, experiences of patients with EPM on AREN0533, as well as on protocols AREN03B2 and NWTS-5, were reviewed. METHODS: Combined outcomes for patients with EPM from NWTS-5, AREN0533, and AREN03B2 were determined. Those treated on AREN0533 were compared with those treated on NWTS-5. Prognostic factors were explored in the pooled cohort. RESULTS: Forty-seven patients with FHWT with EPM enrolled on AREN0533, 37 enrolled on NWTS-5, and 64 were followed only on AREN03B2. The pooled cohort of all 148 patients demonstrated a 4-year event-free survival (EFS) of 77.3% (95% CI, 70.8-84.4) and 4-year overall survival of 88.9% (95% CI, 83.9-94.2). Four-year EFS of patients with EPM treated on AREN0533 was 76.0% (95% CI, 64.6-89.4) vs 64.9% (95% CI, 51.7-82.2) on NWTS-5; hazard ratio, 0.64, p = .26; no difference in overall survival was observed. Increasing linear age and slow incomplete lung response were associated with worse EFS in a pooled cohort. CONCLUSIONS: Outcomes for patients with EPM are among the lowest for children with FHWT. Further trials with standardized surgical and radiation treatment to metastatic sites, and prospectively collected biologic and treatment details are needed. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov identifiers: NCT00379340, NCT00898365, and NCT00002611.

Pursuit of the optimal therapeutic approach and intensity for children with bilateral Wilms tumour.

Investigators from the International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) report on outcomes of children with bilateral Wilms tumour treated on the SIOP 2001 study. They demonstrate that vincristine and actinomycin-D induction chemotherapy is sufficient in a subset of children, but most required additional agents during their treatment.

Characteristics and outcome of synchronous bilateral Wilms tumour in the SIOP WT 2001 Study: Report from the SIOP Renal Tumour Study Group (SIOP-RTSG).

BACKGROUND: Among patients with nephroblastoma, those with bilateral disease are a unique population where maximising tumour control must be balanced with preserving renal parenchyma. METHODS: The SIOP 2001 protocol recommended surgery after neoadjuvant cycle(s) of Dactinomycin and Vincristine (AV) with response-adapted intensification, if needed. Adjuvant treatment was given based on the lesion with the worst histology. RESULTS: Three hundred and twenty seven patients with stage V disease were evaluable: 174 had bilateral Wilms tumour (BWT), 101 unilateral WT and contralateral nephroblastomatosis (NB) and 52 bilateral nephroblastomatosis. In these three groups, the estimated 5y-EFS was 76.1%, 84.6%, and 74.9%, respectively. AV chemotherapy alone was the successful chemotherapy for 58.7% of all the patients and 65.6% of the non-metastatic patients. Among the 174 patients with BWT, 149 (88.2%) had at least one nephron-sparing surgery. Twenty of 61 bilateral stage I patients were treated with four-week AV postoperatively achieving 94.4% 5y-EFS. At last follow-up, 87% of patients had normal renal function. CONCLUSIONS: This study demonstrates that AV without anthracyclines is sufficient to achieve NSS and good survival in the majority of patients. For patients with bilateral stage I WT and intermediate risk histology, only four weeks adjuvant AV seems to be sufficient. CLINICAL TRIAL REGISTRATION: NCT00047138.

A Gradual Transition Toward Anaplasia in Wilms Tumor Through Tolerance to Genetic Damage.

Patients with Wilms tumor (WT) in general have excellent survival, but the prognosis of patients belonging to the subgroup of WT with diffuse anaplasia (DA) is poor due to frequent resistance to chemotherapy. We hypothesized that DA WT cells might undergo changes, such as acquiring a persistent tolerance to DNA damage and copy number aberrations (CNAs), which could eventually lead to their resistance to chemotherapy treatment. Tissue sections from chemotherapy-treated DA WTs (n = 12) were compared with chemotherapy-treated nonanaplastic WTs (n = 15) in a tissue microarray system, enabling analysis of 769 tumor regions. All regions were scored for anaplastic features and immunohistochemistry was used to quantify p53 expression, proliferation index (Ki67), and DNA double-strand breaks (γH2AX). CNAs were assessed by array-based genotyping and TP53 mutations using targeted sequencing. Proliferation index and the frequency of DNA double-strand breaks (γH2AX dot expression) increased with higher anaplasia scores. Almost all (95.6%) areas with full-scale anaplasia had TP53 mutations or loss of heterozygosity, along with an increased amount of CNAs. Interestingly, areas with wild-type TP53 with loss of heterozygosity and only one feature of anaplasia (anaplasia score 1) also had significantly higher proliferation indices, more DNA double-strand breaks, and more CNAs than regions without any anaplastic features (score 0); such areas may be preanaplastic cell populations under selective pressure for TP53 mutations. In conclusion, we suggest that chemoresistance of DA WTs may be partly explained by a high proliferative capability of anaplastic cells, which also have a high burden of double-stranded DNA breaks and CNAs, and that there is a gradual emergence of anaplasia in WT.

Surgical Management of Wilms Tumors with Intravenous Extension: A Multicenter Analysis of Clinical Management with Technical Insights.

BACKGROUND: About 5% of Wilms tumors present with vascular extension, which sometimes extends to the right atrium. Vascular extension does not affect the prognosis, but impacts the surgical strategy, which is complex and not fully standardized. Our goal is to identify elements of successful surgical management of Wilms tumors with vascular extensions. PATIENTS AND METHODS: A retrospective study of pediatric Wilms tumors treated at three sites (January 1999-June 2019) was conducted. The inclusion criterion was the presence of a renal vein and vena cava thrombus at diagnosis. Tumor stage, pre and postoperative treatment, preoperative imaging, operative report, pathology, operative complications, and follow-up data were reviewed. RESULTS: Of the 696 pediatric patients with Wilms tumors, 69 (9.9%) met the inclusion criterion. In total, 24 patients (37.5%) had a right atrial extension and two presented with Budd-Chiari syndrome at diagnosis. Two died at diagnosis owing to pulmonary embolism. All patients received neoadjuvant chemotherapy and thrombus regressed in 35.6% of cases. Overall, 14 patients had persistent intra-atrial thrombus extension (58%) and underwent cardiopulmonary bypass. Most thrombi (72%) were removed intact with nephrectomy. Massive intraoperative bleeding occurred during three procedures. Postoperative renal insufficiency was identified as a risk factor for patient survival (p = 0.01). With a median follow-up of 9 years (range: 0.5-20 years), overall survival was 89% and event-free survival was 78%. CONCLUSIONS: Neoadjuvant chemotherapy with proper surgical strategy resulted in a survival rate comparable to that of children with Wilms tumors without intravascular extension. Clinicians should be aware that postoperative renal insufficiency is associated with worse survival outcomes.

Screening of potential hub genes involved in Kidney Wilms tumor via bioinformatics analysis and experimental validation.

BACKGROUND: Wilms tumor (WT) is the most common pediatric embryonal tumor. Improving patient outcomes requires advances in understanding and targeting the multiple genes and cellular control pathways, but its pathogenesis is currently not well-researched. We aimed to identify the potential molecular biological mechanism of WT and develop new prognostic markers and molecular targets by comparing gene expression profiles of Wilms tumors and fetal normal kidneys. METHODS: Differential gene expression analysis was performed on Wilms tumor transcriptomic data from the GEO and TARGET databases. For biological functional analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were utilized. Out of 24 hub genes identified, nine were found to be prognostic-related through univariate Cox regression analysis. These nine genes underwent LASSO regression analysis to enhance the predictive capability of the model. The key hub genes were validated in the GSE73209 datasets, and cell function experiments were conducted to identify the genes' functions in WiT-49 cells. RESULTS: The enrichment analysis revealed that DEGs were significantly involved in the regulation of angiogenesis and regulation of cell differentiation. 24 DEGs were identified through PPI networks and the MCODE algorithm, and 9 of 24 genes were related to WT patients' prognosis. EMCN and CCNA1 were identified as key hub genes, and related to the progression of WT. Functionally, over-expression of EMCN and CCNA1 knockdown inhibited cell viability, proliferation, migration, and invasion of Wilms tumor cells. CONCLUSIONS: EMCN and CCNA1 were identified as key prognostic markers in Wilms tumor, suggesting their potential as therapeutic targets. Differential gene expression and enrichment analyses indicate significant roles in angiogenesis and cell differentiation.

Further evidence that the neurodevelopmental gene FBXW7 predisposes to Wilms tumor.

Somatic variants in the NOTCH pathway regulator FBXW7 are frequently seen in a variety of malignancies. Heterozygous loss-of-function germline variants in FBXW7 have recently been described as causative for a neurodevelopmental syndrome. Independently, FBXW7 was also considered as a susceptibility gene for Wilms tumor due to a few observations of heterozygous germline variants in patients with Wilms tumor. Whether the same FBXW7 variants are implicated in both, neurodevelopmental delay and Wilms tumor formation, remained unclear. By clinical testing, we now observed a patient with neurodevelopmental delay due to a de novo constitutional mosaic FBXW7 splice site pathogenic variant who developed Wilms tumor. In the tumor, we identified a second hit frameshift variant in FBXW7. Immunohistochemical staining was consistent with mosaic loss of FBXW7 protein expression in the tumor. Our data support the role of constitutional FBXW7 pathogenic variants in both, neurodevelopmental disorder and the etiology of Wilms tumor. Therefore, Wilms tumor screening should be considered in individuals with constitutional or germline pathogenic variants in FBXW7 and associated neurodevelopmental syndrome.

LncRNA LINC01339 Hinders the Development of Wilms' Tumor via MiR-135b-3p/ADH1C Axis.

Wilms' tumor is a malignant renal cancer that arises within the pediatric urinary system. This study intended to investigate how a novel long non-coding RNA LINC01339 functions in the pathogenesis of Wilms' tumor. An elevated miR-135b-3p expression as well as reduced levels of LINC01339 and ADH1C were observed in Wilms' tumor. LINC01339 mediated ADH1C expression by directly binding to miR-135b-3p. The enforced LINC01339 or ADH1C markedly hindered cell growth and migration in Wilms' tumor. The LINC01339 overexpression also repressed the growth of Wilms' tumors in vivo, whereas miR-135b-3p overexpression exerted the opposite effects on Wilms' tumor cells in vitro. Additionally, upregulating miR-135b-3p reversed LINC01339's effects on the cellular processes of Wilms' tumor cells, whereas ADH1C overexpression offset the cancer-promoting influence of miR-135b-3p upregulation on Wilms' tumor progression. Therefore, LINC01339 prevents Wilms' tumor progression by modulating the miR-135b-3p/ADH1C axis. Our findings substantiate that the LINC01339/miR-135 b-3p/ADH1C regulatory axis has potential to be a target for the treatment of Wilms' tumor.

Prognostic impact of pre-referral tumor resection in unilateral Wilms tumor: A single-institute experience from a lower middle-income country.

INTRODUCTION: The objectives of this study were to evaluate the prognostic impact of pre-referral surgical resection of Wilms tumor (WT) performed at non-oncology centers, and to strategize an improved care plan for this very curable pediatric tumor. METHODS: In this study conducted in a large pediatric cancer center in Pakistan, we retrospectively reviewed the electronic medical records (EMR) of 149 patients with unilateral WT from September 2008 to August 2017. Based on treatment approach, patients were categorized into two groups: (i) pre-referral tumor resection (PTR: n = 75), and (ii) post-neoadjuvant chemo nephrectomy (PCN: n = 74). RESULTS: The proportion of metastatic disease in PTR and PCN groups was 33.3% and 35.1%, respectively. In the PTR subset, median time to admission after PTR was 5 weeks (mean 11, SEM 2.8, range: 2-202) weeks, with 53.3% (n = 40) presenting more than 4 weeks after PTR. Twenty patients had no cross-sectional imaging prior to PTR and underwent surgery after abdominal ultrasound only. On baseline imaging at our center, 58.7% (n = 44) of the PTR group had radiologically evaluable disease (four metastases only, 19 local residual tumor only, 21 both localized tumor and visible metastases). Disease staging was uncertain in 23 patients because of no or inadequate histology specimens and/or lymph node sampling in patients with no evaluable disease. Statistically significant differences were recorded for the two subsets regarding tumor volume, extent and nodularity, renal vein and renal sinus involvement, lymph node status, tumor rupture and histopathologic features, and tumor stage, with a 10-year event-free survival (EFS) for PCN and PTR of 74.3% and 50.7%, respectively (p < .001). In the PTR group, EFS for those presenting within 4 weeks and later was 91.4% versus 15.0%, respectively (p < .0001). CONCLUSION: Suboptimal pre-referral surgical intervention results in poor survival outcomes in unilateral WT. Our findings highlight the need for a comprehensive action plan for educating healthcare professionals engaged in WT diagnosis and referral process. PCN in a multidisciplinary team approach can reduce surgical morbidity and seems to be a better strategy to improve the survival rates in low-resource settings.

Lung relapse pattern in children with metastatic Wilms tumor.

Wilms tumor is the most common pediatric renal cancer, and lungs represent the major site of metastasis and recurrence. Relapse occurs in 15%, months or years after treatment; so due to the small sample, acquiring more data about the pattern of lung relapse remains a challenge. The aim of our study was to evaluate if pulmonary relapse, detected by computed tomography (CT), occurred at the initial site of lung metastases or in a different location. According to our data, the CT pattern of lung relapse showed high probability of recurrence at the same site of initial metastasis.

Concomitant Wilms tumor and autosomal dominant polycystic kidney disease.

BACKGROUND: Concomitant Wilms tumor (WT) and autosomal dominant polycystic kidney disease (ADPKD) is exceedingly rare, presenting a diagnostic and technical challenge to pediatric surgical oncologists. The simultaneous workup and management of these disease processes are incompletely described. PROCEDURE: We performed a retrospective analysis of patients treated at our institution with concomitant diagnoses of WT and ADPKD. We also review the literature on the underlying biology and management principles of these conditions. RESULTS: We present three diverse cases of concomitant unilateral WT and ADPKD who underwent nephrectomy. One patient had preoperative imaging consistent with ADPKD with confirmatory testing postoperatively, one was found to have contralateral renal cysts intraoperatively with confirmatory imaging post nephrectomy, and one was diagnosed in childhood post nephrectomy. All patients are alive at last follow-up, and the patient with longest follow-up has progressed to end-stage kidney failure requiring transplantation and dialysis in adulthood. All patients underwent germline testing and were found to have no cancer predisposition syndrome or pathogenic or likely pathogenic variants for WT. CONCLUSION: Concomitant inheritance of ADPKD and development of WT are extremely rare, and manifestations of ADPKD may not present until late childhood or adulthood. ADPKD is not a known predisposing condition for WT. When ADPKD diagnosis is made by family history, imaging, and/or genetic testing before WT diagnosis and treatment, the need for extensive preoperative characterization of cystic kidney lesions in children and increased risk of post-nephrectomy kidney failure warrant further discussion of surgical approach and perioperative management strategies.

Anaplasia in Wilms tumor: A critical review.

Anaplasia in Wilms tumor is recognized as the most important prognostically unfavorable histological feature. It is subtyped as focal anaplastic Wilms tumor (FAWT) and diffuse anaplastic Wilms tumor (DAWT). Outcomes of patients with DAWT remain poor in patients with stage III and IV tumors. Important issues relevant to anaplasia in Wilms tumor, including prevalence, treatment, outcomes, biomarkers, anaplasia, and chemotherapy, and the concept of tumor aggressiveness, are reviewed and discussed here. We also consider the differences in clinical approaches to anaplasia in Wilms tumor between the two major renal tumor clinical research groups: the International Society of Paediatric Oncology (SIOP) Renal Tumour Study Group and the Children's Oncology Group (COG) Renal Tumor Group. We emphasize the importance and implications of recognizing FAWT and DAWT as separate clinico-pathological entities.

Bilateral Wilms tumor with anaplasia: A report from the Children's Oncology Group Study AREN0534.

INTRODUCTION: The purpose of this study is to examine the outcomes in children with anaplastic bilateral Wilms tumor (BWT) from study AREN0534 in order to define potential prognostic factors and areas to target in future clinical trials. METHODS: Demographic and clinical data from AREN0534 study patients with anaplasia (focal anaplasia [FA], or diffuse anaplasia [DA]) were compared. Event-free survival (EFS) and overall survival (OS) were reported using Kaplan-Meier estimation with 95% confidence bands, and differences in outcomes between FA and DA compared using log-rank tests. The impact of margin status was analyzed. RESULTS: Twenty-seven children who enrolled on AREN0534 had evidence of anaplasia (17 DA, 10 FA) in at least one kidney and were included in this analysis. Twenty-six (96%) had BWT. Nineteen percent had anaplastic histology in both kidneys (four of 17 DA, and one of 10 FA). Forty-six percent with BWT had bilateral nephron-sparing surgery (NSS); one child who went off protocol therapy, eventually required bilateral completion nephrectomies. Median follow-up for EFS and OS was 8.6 and 8.7 years from enrollment. Four- and 8-year EFS was 53% [95% confidence interval (CI): 34%-83%] for DA; 4-year EFS was 80% [95% CI: 59%-100%], and 8-year EFS 70% [95% CI: 47%-100%] for FA. Three out of 10 children with FA and eight out of 17 children with DA had events. EFS did not differ statistically by margin status (p = .79; HR = 0.88). Among the six children who died (five DA, one FA), all experienced prior relapse or progression within 18 months. CONCLUSION: Events in children with DA/FA in the setting of BWT occurred early. Caution should be taken about interpreting the impact of margin status outcomes in the context of contemporary multimodal therapy. Future targeted investigations in children with BWT and DA/FA are needed.

Wilms tumor characteristics, surgical management, outcomes, and chronic kidney disease in children with WAGR syndrome: A report from the International WAGR Syndrome Association survey.

INTRODUCTION: Children with WAGR (Wilms tumor, aniridia, genitourinary anomalies, and range of development delays) syndrome are predisposed to Wilms tumor (WT) and intrinsic kidney disease. Using the comprehensive International WAGR Syndrome Association (IWSA) survey of children with WAGR syndrome, we analyzed tumor characteristics, treatment and congenital risk factors, and kidney function in children with WAGR and WT. METHODS: Descriptive statistics were utilized including demographics, treatment strategies, and patient outcomes. Comparisons were made between patients with WAGR and WT to those with WAGR alone. A multivariable logistic regression was completed for risk of developing WT and to identify predictors of chronic kidney disease (CKD). RESULTS: Sixty-four of 145 children with WAGR developed WT (44.1%). Three relapsed and one died. CKD developed in five children with WAGR without WT (5/81, 6.2%), and in 34 with WAGR and WT (34/64, 28.3%). Children with WAGR and WT were younger (p = .017), and had a greater association with CKD than WAGR children without WT (p < .0001). Two children with WT required hemodialysis, and one underwent kidney transplantation. By univariate analysis, CKD at any stage was associated with complete nephrectomy for the WT surgery (p < .0001), chemotherapy duration greater than 12 months, and three-drug therapy. Upon multivariate analysis, prior nephrectomy was the only significant variable (p = .0002). CONCLUSIONS: Epidemiological analysis of children with WAGR demonstrated favorable oncologic outcomes, but high rate of early CKD in those who developed WT. Further study of the use of nephron-sparing surgery in children with WAGR and strategies to delay or treat early CKD are needed.

The rationale for nephron-sparing surgery in unilateral non-syndromic Wilms tumour.

The central question of nephron-sparing surgery in unilateral non-syndromic Wilms tumour sits at a crossroads between surgery, oncology, and nephrology. There has been a significant paradigm shift in paediatric oncology towards reducing toxicity and addressing long-term treatment-related sequalae amongst childhood cancer survivors. After paediatric nephrectomy and 30-50 years of follow-up, 40% of patients will have chronic kidney disease, including 22% with hypertension and 23% with albuminuria. It is difficult to predict which patients will progress to develop hypertension, reduced glomerular filtration rate, albuminuria, and a higher cardiovascular risk. For these reasons, nephron-sparing surgery when it is technically feasible must be considered. To decrease the incidence of positive surgical margins (viable tumour present at a resection margin), incomplete lymph node sampling, and complications, these procedures should be performed at specialist and experienced reference centres. Based on the impacts of individual treatment pathways, survivors of childhood WT need to be followed through adulthood for early detection of chronic kidney disease, hypertension, and prevention of cardiovascular events.

Wilms Tumor With Raised Serum Alpha-Fetoprotein: Highlighting the Need for Novel Circulating Biomarkers.

Wilms tumor (WT) is the commonest cause of renal cancer in children. In Europe, a diagnosis is made for most cases on typical clinical and radiological findings, prior to pre-operative chemotherapy. Here, we describe a case of a young boy presenting with a large abdominal tumor, associated with raised serum alpha-fetoprotein (AFP) levels at diagnosis. Given the atypical features present, a biopsy was taken, and histology was consistent with WT, showing triphasic WT, with epithelial, stromal, and blastemal elements present, and positive WT1 and CD56 immunohistochemical staining. During pre-operative chemotherapy, serial serum AFP measurements showed further increases, despite a radiological response, before a subsequent fall to normal following nephrectomy. The resection specimen was comprised of ~55% and ~45% stromal and epithelial elements, respectively, with no anaplasia, but immunohistochemistry using AFP staining revealed positive mucinous intestinal epithelium, consistent with the serum AFP observations. The lack of correlation between tumor response and serum AFP levels in this case highlights a more general clinical unmet need to identify WT-specific circulating tumor markers.

Does bilateral Wilms' tumor involving the collecting system in children have a worse prognosis?

BACKGROUND: The literature on nephron-sparing surgery (NSS) in children with bilateral Wilms' tumors (BWT) involving the collection system is mostly comprised of case reports. The present study aimed to summarize the clinical characteristics, treatments, and prognosis of children with BWT involving the collecting system admitted to our pediatric surgery center compared with those whose tumors did not involve the collecting system. A secondary aim was to discuss how to preserve more kidney parenchyma and prevent long-term renal failure under the premise of preventing tumor recurrence. METHODS: Patients with BWT admitted to our pediatric surgery center between January 2008 and June 2022 were reviewed. All included patients were grouped according to the relationship between the tumor and collecting system according to the intraoperative findings. Group I included children with tumor infiltrating the collecting system, group II included children with tumor growing into the collecting system, and group III included children whose tumor did not involve the collecting system. The clinical features, treatments and prognosis of the patients were analyzed. RESULTS: Seventy patients were enrolled, including 20 patients with 25 sides of tumors infiltrating the collecting system in group I,10 patients with 13 sides of tumors growing into the collecting system in group II, and 40 patients in group III. There was no significant difference in patients age and gender between group I and group II. In total, 20 patients in group I and 9 patients in group II had partial response (PR) after neoadjuvant chemotherapy. In group I, 22 of 25 sides of tumors underwent NSS; in group II, 11 of 13 sides of tumors underwent NSS. During an average follow-up of 47 months, in group I, 6/20 patients relapsed and 2/20 patients died; in group II, 3/10 patients relapsed and 1/10 patient died. There was no significant difference in 4-year overall survival (OS) rate among groups I, II and III (86.36% vs. 85.71%vs. 91.40%, P = 0.902). CONCLUSIONS: To preserve renal parenchyma, NSS is feasible for children with BWT involving the collecting system. There was no significant difference in postoperative long-term OS between patients with BWT involving the collecting system and not involving the collecting system.

Horseshoe kidney with teratoid type of Wilms tumor: a rare case report.

BACKGROUND: Horseshoe kidney is the most common renal fusion anomaly, and Wilms tumor is the most frequent renal malignancy in children. The occurrence of Wilms tumor in association with horseshoe kidney is a scarce anomaly. However, the arising of a teratoid type, which is a rare variant of Wilms tumor in a horseshoe kidney, is exceptionally unique. CASE PRESENTATION: This report presents a 5-year-old male admitted with horseshoe kidney involved by a large heterogeneous calcified mass that was diagnose on biopsy as Wilms tumor blastemal dominant. According to the local and regional extension and metastatic tumor in the lungs, the patient underwent neoadjuvant chemotherapy and then surgery. Post-operative pathologic findings confirmed the diagnosis of teratoid Wilms tumor. CONCLUSIONS: The occurrence of renal anomalies associated with a malignancy might be more frequent in the clinical environment. There are numerous differential diagnoses for renal tumors and masses, but the possibility of exceptional anomalies should not be denied, and clinicians should be prepared for these occasions. Although studies propose that chemotherapy has a trivial effect on teratoid Wilms tumors, it is essential to evaluate the tumor for any possibility of regression in non-teratoid regions before proceeding to upfront tumoral resection.