Wilms' tumour is a cancer of the kidney which is very different to adult kidney cancer. Most patients are under 5 years of age at diagnosis, though Wilms' tumour is sometimes seen in older children and occasionally in young adults. In most cases only one kidney has disease (unilateral-Wilms' Tumour); but in some cases both kidneys are affected (bilateral-Wilms' tumour). A small minority of cases are known to be hereditary. Other less common kidney cancers in children include malignant rhabdoid tumours and clear cell sarcoma. Treatment for these is usually similar to that for Wilms' tumour.
Menu: Wilms' Tumour Information for Patients and Family Information for Health Professionals / Researchers Latest Research Publications Malignant Rhabdoid Tumour
This list of publications is regularly updated (Source: PubMed).
Pietras WAdvances and changes in the treatment of children with nephroblastoma.
Adv Clin Exp Med. 2012 Nov-Dec; 21(6):809-820 [PubMed
Wilms' tumor or nephroblastoma is the most common malignant tumor stemming from kidney cells and second only to neuroblastoma when it comes to extracranial solid tumors in children. The results of nephroblastoma treatment are a perfect example of therapeutic success resulting from an interdisciplinary approach to the problem and the cooperation of pediatric surgeons, pediatric oncologists, pathologists, radiologists and radiotherapists leading to precise diagnoses and the selection of the optimal treatment. At the end of the sixties, international research teams began studying the best treatment for this tumor in children. In Europe, it was the International Society of Paediatric Oncology (SIOP), which has used the working name SIOP- RTSG (Renal Tumor Study Group - Group for the Study of Kidney tumors) since 2008 and in North America NWTS (National Wilms' Tumor Study - The National Committee for Research on Wilms' tumor). Summarizing the experience and knowledge on the treatment of nephroblastoma, it should be noted that, despite years of research and information exchange, uniform guidelines have not yet been developed, and there are still differences in treatment of this tumor. The biggest differences are between the "American" treatment recommended by the NWTS and the "European" by SIOP. In the first it is recommended to start treatment from the surgical removal of the tumor, even in the case of disseminated disease with the presence of metastases in the lungs. The treatment method is chosen by the institution managing the patient; for this reason on the American continent in Brazil, Wilms' tumor is treated according to the recommendations of "European" protocols (SIOP) and some institutions in Europe, for example in Italy, treat patients with nephroblastoma according to the "American" protocols recommended by the NWTS; until recently, focal disease was treated with primary nephrectomy in the UK.
Okur A, Pinarli FG, Karadeniz C, et al.Familial synchronous bilateral teratoid Wilms tumor with elevated alpha-fetoprotein level.
Tumori. 2012; 98(6):179e-82e [PubMed
Familial Wilms tumor is a rare entity that accounts for only 1-2% of all Wilms tumor cases, with an earlier age of onset and an increased frequency of bilateral tumors. Teratoid Wilms tumor is a variant of nephroblastoma with a predominance of heterologous tissues comprising more than 50% of the tumor volume. Wilms tumor does not usually secrete any specific tumor marker and all teratoid Wilms tumor cases previously reported were sporadic non-secreting neoplasms. Here we describe an infant with familial synchronous bilateral teratoid Wilms tumor whose serum alpha-fetoprotein level was elevated. To our knowledge, this extremely rare type of case is reported for the first time in the literature.
Ehrlich PF, Anderson JR, Ritchey ML, et al.Clinicopathologic findings predictive of relapse in children with stage III favorable-histology Wilms tumor.
J Clin Oncol. 2013; 31(9):1196-201 [PubMed
] Article available free on PMC
PURPOSE: Stage III designation in NWTS-5 (National Wilms Tumor Study-5) was determined by four pathologic criteria: positive lymph nodes (LNs), peritoneal implants, residual disease, and tumor rupture. The objective of this study was to determine the prognostic significance of each of the stage III criteria.
PATIENTS AND METHODS: Children with stage III Wilms tumor (WT) treated in NWTS-5 were assessed for event-free (EFS) and overall survival (OS). Sites of relapse and molecular status of tumors are reported. EFS and OS are reported 8 years after diagnosis.
RESULTS: There were 569 patients with local stage III favorable-histology (FH) WT in this analysis, of whom 109 had overall stage IV disease. LN involvement alone was the most frequent criterion for stage III designation (38%), followed by microscopic residual disease alone (20%), microscopic residual disease and LN involvement (14%), and spill or soilage alone (9%). The 8-year EFS and OS estimates for all patients with local stage III FHWT were 82% and 91%, respectively. Multivariate analysis demonstrated that both LN involvement (relative risk, 1.89; P = .005) and microscopic residual disease (relative risk, 1.87; P = .007) were predictive of EFS, and OS results were similar. There was no apparent difference in pattern of relapse according to stage III subtype. The rate of loss of heterozygosity was higher (6%) for those with positive LNs than for those without (2%; P = .05).
CONCLUSION: LN involvement and microscopic residual are the stage III criteria highly predictive of EFS and OS for patients with stage III FHWT. It is possible that in future studies, patients with different stage III criteria may receive different therapies.
Cao X, Liu D, Yan X, et al.Stat3 inhibits WTX expression through up-regulation of microRNA-370 in Wilms tumor.
FEBS Lett. 2013; 587(6):639-44 [PubMed
Wilms tumor (WT) is a genetically heterogeneous childhood kidney tumor. Several genetic mutations have been identified in WT patients, including inactivation of WTX, somatic stabilizing CTNNB1, and p53 mutations. However, the molecular mechanisms in tumorigenesis remain largely unexplored. Stat3 is a transcription factor that can promote oncogenesis. Stat3 activation is commonly viewed as crucial for multiple tumor proliferation and metastasis. We show that Stat3 is highly activated in Wilms tumor tissues compared to those in adjacent tissues. IL-6 treatment or transfection of a constitutively activated Stat3 in G401 cells promotes cell proliferation. At the molecular level, we further elucidate that Stat3 inhibits WTX expression through up-regulation of microRNA-370. Our results suggest that Stat3/miR-370/WTX regulatory axis might be a critical mechanism in Wilms tumor cells.
Shahidul Makki M, Cristy Ruteshouser E, Huff VUbiquitin specific protease 18 (Usp18) is a WT1 transcriptional target.
Exp Cell Res. 2013; 319(5):612-22 [PubMed
Wilms tumor gene WT1 encodes a zinc finger-containing transcription factor which is required for renal development. Mutations in WT1 are observed in 20% of Wilms tumors (a pediatric kidney cancer), but the in vivo WT1 targets and associated molecular pathways involved in the etiology of Wilms tumor are still elusive. To identify WT1 targets we performed genome-wide comprehensive expression profiling using Affymetrix Gene Chip Mouse Genome 430 2.0 Arrays, comparing E13.5 mouse kidneys in which Wt1 had been somatically ablated with littermate controls. We identified Usp18 as the most differentially expressed gene in mutant kidney. Using tetracycline inducible cells we demonstrated a repressive effect of WT1 on USP18 expression. Conversely, knockdown of WT1 led to the upregulation of Usp18. Furthermore, direct binding of WT1 to the Usp18 promoter was demonstrated by ChIP assay. Overexpression of USP18 in murine and human cell lines resulted in cell proliferation. Additionally, Usp18 upregulation was observed in a mouse model of Wilms tumor. Taken together our data demonstrate that Usp18 is a transcriptional target of WT1 and suggest that increased expression of USP18 following WT1 loss contributes to Wilms tumorigenesis.
Rodríguez-López R, Pérez JM, Balsera AM, et al.The modifier effect of the BDNF gene in the phenotype of the WAGRO syndrome.
Gene. 2013; 516(2):285-90 [PubMed
Individuals who are carriers of deletions of various sizes that cause haploinsufficiency in the contiguous WT1 and PAX6 genes, located on chromosome 11p13 approximately 4 Mb centromeric to the BDNF gene, are susceptible to Wilms tumor, aniridia, mental retardation, genitourinary anomalies and obesity (WAGRO syndrome). The molecular characterization of the wide deletion 11p15.1p12 arr (18676926-36576388) x1 dn in a child with 3 years and 4 months of age only affected by aniridia, predicts not only other serious associated diseases, but also allows us to hypothesize a specific phenotype of mental impairment, conduct alterations and childhood obesity, possibly added to the onset of metabolic alterations. The variable appearance and/or description of haploinsufficiency for obesity susceptibility in the WAGR syndrome mainly depends on the critical region located within 80 kb of exon 1 of BDNF. The relationship between genetic variation based on the genotype combinations of the 4 gene SNPs tagging the BDNF gene and the body mass index (BMI) was studied. The polymorphic variability was similarly distributed in 218 children suffering a severe and non-syndromic obesity from families at high risk for obesity, as compared with 198 controls. The corroborated role of the BDNF gene as highly susceptible to severe syndromic obesity has not already been evidenced in the molecular basis of overweight attributed to the common polygenic principles. Its potential role as risk modifier variant to provoke more severe phenotype has not yet been demonstrated. Some genetic variants of brain-derived neurotrophic factor (BDNF) have resulted in important disorders of energy balance, but it is essential to know exactly their deleterious human capacity because they play a fundamental role in the development and plasticity of the central nervous system in regulating food intake. The existence of polymorphic amino acid changes of unknown functional significance in patients carrying the haploinsufficiency of the BDNF gene could constitute an adequate model to study in depth their effects.
Khanna G, Naranjo A, Hoffer F, et al.Detection of preoperative wilms tumor rupture with CT: a report from the Children's Oncology Group.
Radiology. 2013; 266(2):610-7 [PubMed
] Article available free on PMC
PURPOSE: To retrospectively determine the diagnostic performance of computed tomography (CT) in identifying the presence or absence of preoperative Wilms tumor rupture.
MATERIALS AND METHODS: The cohort was derived from the AREN03B2 study of the Children's Oncology Group. The study was approved by the institutional review board and was compliant with HIPAA. Written informed consent was obtained before enrollment. The diagnosis of Wilms tumor rupture was established by central review of notes from surgery and/or pathologic examination. Seventy Wilms tumor cases with rupture were matched to 70 Wilms tumor controls without rupture according to age and tumor weight (within 6 months and 50 g, respectively). CT scans were independently reviewed by two radiologists, and the following CT findings were assessed: poorly circumscribed mass, perinephric fat stranding, peritumoral fat planes obscured, retroperitoneal fluid (subcapsular vs extracapsular), ascites beyond the cul-de-sac, peritoneal implants, ipsilateral pleural effusion, and intratumoral hemorrhage. All fluids were classified as hemorrhagic or nonhemorrhagic by using a cutoff of 30 HU. The relationship between CT findings and rupture was assessed with logistic regression models.
RESULTS: The sensitivity and specificity for detecting Wilms tumor rupture were 54% (36 of 67 cases) and 88% (61 of 69 cases), respectively, for reviewer 1 and 70% (47 of 67 cases) and 88% (61 of 69 cases), respectively, for reviewer 2. Interobserver agreement was substantial (ĸ = 0.76). All imaging signs tested, except peritoneal implants, intratumoral hemorrhage, and subcapsular fluid, showed a significant association with rupture (P ≤ .02). The attenuation of ascitic fluid did not have a significant correlation with rupture (P = .9990). Ascites beyond the cul-de-sac was the single best indicator of rupture for both reviewers, followed by perinephric fat stranding and retroperitoneal fluid for reviewers 1 and 2, respectively (P < .01).
CONCLUSION: CT has moderate specificity but relatively low sensitivity in the detection of preoperative Wilms tumor rupture. Ascites beyond the cul-de-sac, irrespective of attenuation, is most predictive of rupture.
Spreafico F, Gamba B, Mariani L, et al.Loss of heterozygosity analysis at different chromosome regions in Wilms tumor confirms 1p allelic loss as a marker of worse prognosis: a study from the Italian Association of Pediatric Hematology and Oncology.
J Urol. 2013; 189(1):260-6 [PubMed
PURPOSE: The specific aims of the AIEOP-TW-2003 protocol included prospectively investigating a possible association of tumor loss of heterozygosity with outcomes in children treated for Wilms tumor.
MATERIALS AND METHODS: We analyzed 125 unilateral favorable histology Wilms tumors registered between 2003 and 2008 in the Italian cooperative protocol for microsatellite markers mapped to chromosomes 1p, 7p, 11q, 16q and 22q.
RESULTS: The 3-year disease-free survival and overall survival probabilities were 0.87 (95% CI 0.81-0.93) and 0.98 (95% CI 0.96-1.0), respectively. Loss of heterozygosity at 1p was significantly associated with a worse disease-free survival (probability 0.67 for patients with and 0.92 for those without 1p loss of heterozygosity, p = 0.0009), as confirmed also by multivariate analysis adjusting for tumor stage and patient age at diagnosis. There was no difference in disease-free survival probability among children with loss of heterozygosity in the other chromosomal regions tested. The worse outlook for children older than 2 years at diagnosis did not seem to be influenced by the loss of heterozygosity patterns considered.
CONCLUSIONS: Chromosome 1p loss of heterozygosity seems to be a risk factor for nonanaplastic Wilms tumor, possibly regardless of other clinical factors. Our findings were uninformative regarding loss of heterozygosity in the other chromosomal regions tested.
Li ZZ, Xing L, Zhao ZZ, et al.Decrease of renal aquaporins 1-4 is associated with renal function impairment in pediatric congenital hydronephrosis.
World J Pediatr. 2012; 8(4):335-41 [PubMed
BACKGROUND: Renal aquaporins (AQP1-4) concentration is downregulated and is in proportion to the degree of hydronephrosis graded by ultrasound in pediatric congenital hydronephrosis (CH). However, the relationship between the expression of AQP1-4 with the changes of renal function impairment (RFI) evaluated by (99m)Tc-DTPA renal dynamic imaging is still unclear. This study aimed to investigate the relationship between AQP1-4 expression and degree of RFI in children with CH.
METHODS: The expression of AQP1-4 was evaluated in 45 children with unilateral ureteropelvic junction obstruction (28 boys and 17 girls, average age: 28±10 months) and 15 children undergoing nephrectomy for nephroblastoma (8 boys and 7 girls, average age: 26±8 months) by immunoblotting and immunohistochemistry. Renal function was graded into mild and severe RFI by (99m)Tc-DTPA renal dynamic imaging.
RESULTS: One-way analysis of variance with Bonferonni's correction showed a significantly reduced protein expression of AQP1-4 in the severe RFI group compared with those in both mild RFI group and controls (AQP1: 0.52±0.09 vs. 0.91±0.06 vs. 1.23±0.033; AQP2: 0.68±0.12 vs. 1.09±0.06 vs. 1.52±0.08; AQP3: 0.59±0.16 vs. 0.94±0.08 vs. 1.31±0.07; AQP4: 0.64±0.06 vs. 1.14±0.07 vs. 1.61±0.07; P<0.001, respectively). In kidneys with severe RFI, there was a reduction in the protein concentration of all four AQP isoforms which was more pronounced compared with those seen in kidneys with mild RFI and in the controls.
CONCLUSION: AQP1-4 expression is reduced in proportion with the impairment degree of renal function graded by (99m)Tc-DTPA renal dynamic imaging in human CH.
Cho EH, Kim SY, Kim JKA case of 9.7 Mb terminal Xp deletion including OA1 locus associated with contiguous gene syndrome.
J Korean Med Sci. 2012; 27(10):1273-7 [PubMed
] Article available free on PMC
Terminal or interstitial deletions of Xp (Xp22.2→Xpter) in males have been recognized as a cause of contiguous gene syndromes showing variable association of apparently unrelated clinical manifestations such as Leri-Weill dyschondrosteosis (SHOX), chondrodysplasia punctata (CDPX1), mental retardation (NLGN4), ichthyosis (STS), Kallmann syndrome (KAL1), and ocular albinism (GPR143). Here we present a case of a 13.5 yr old boy and sister with a same terminal deletion of Xp22.2 resulting in the absence of genes from the telomere of Xp to GPR143 of Xp22. The boy manifested the findings of all of the disorders mentioned above. We began a testosterone enanthate monthly replacement therapy. His sister, 11 yr old, manifested only Leri-Weill dyschondrosteosis, and had engaged in growth hormone therapy for 3 yr. To the best of our knowledge, this is the first report of a male with a 9.7 Mb terminal Xp deletion including the OA1 locus in Korea.
Seifert RP, McNab P, Sexton WJ, et al.Rhabdomyomatous differentiation in Wilms tumor pulmonary metastases: a case report and literature review.
Ann Clin Lab Sci. 2012; 42(4):409-16 [PubMed
While sparsely reported in the literature, Wilms tumor may differentiate into more mature mesenchymal tissue types, such as skeletal muscle, following chemotherapy. The frequency of this event is unknown. Chemotherapy and radiation may induce cytodifferentiation of Wilms tumor cells or select for the survival of less mitotically active cells. In follow-up biopsies, the presence of rhabdomyomatous differentiation can confound the histologic diagnosis. Furthermore, these differentiated tumors appear to be more resistant to chemotherapy, thus biopsy and positron emission tomography scans following chemotherapy and radiation may prevent unnecessary treatment. We report an unusual case of Wilms tumor in a 21- year-old man with rhabdomyomatous differentiation of pulmonary metastases after chemotherapy, which presented a challenge during frozen section diagnosis.
Li K, Xiao X, Gao J, et al.Pelvic Wilms tumor in a child with an absent right kidney and spinal malformations.
J Pediatr Surg. 2012; 47(10):e11-4 [PubMed
Wilms tumor rarely occurs in other sites outside the kidney. Various congenital malformations often accompany Wilms tumor, but spinal deformations are rarely seen. We report a very rare association of multiple spinal malformations, right kidney absence, and pelvic Wilms tumor in a 21-month-old girl. The report includes a brief review of relevant literature.
Georgiadi ECh, Dionysiou DD, Graf N, Stamatakos GSTowards in silico oncology: adapting a four dimensional nephroblastoma treatment model to a clinical trial case based on multi-method sensitivity analysis.
Comput Biol Med. 2012; 42(11):1064-78 [PubMed
In the past decades a great progress in cancer research has been made although medical treatment is still widely based on empirically established protocols which have many limitations. Computational models address such limitations by providing insight into the complex biological mechanisms of tumor progression. A set of clinically-oriented, multiscale models of solid tumor dynamics has been developed by the In Silico Oncology Group (ISOG), Institute of Communication and Computer Systems (ICCS)-National Technical University of Athens (NTUA) to study cancer growth and response to treatment. Within this context using certain representative parameter values, tumor growth and response have been modeled under a cancer preoperative chemotherapy protocol in the framework of the SIOP 2001/GPOH clinical trial. A thorough cross-method sensitivity analysis of the model has been performed. Based on the sensitivity analysis results, a reasonable adaptation of the values of the model parameters to a real clinical case of bilateral nephroblastomatosis has been achieved. The analysis presented supports the potential of the model for the study and eventually the future design of personalized treatment schemes and/or schedules using the data obtained from in vitro experiments and clinical studies.
Vaideeswar P, Chaudhari JPWilms' tumor with right heart extension: report of a post-chemotherapeutic fatality.
Indian J Pathol Microbiol. 2012 Jul-Sep; 55(3):381-3 [PubMed
Wilms' tumor (WT) has a strong propensity to invade the vasculature in the form of tumor-thrombus, into the renal veins, and inferior vena cava and even into the right atrium. This cavo-atrial propagation does not alter the prognosis and pre-operative chemotherapy produces shrinkage to the extent of even disappearance of caval or atrial extensions. We present a case of sudden death due to hemorrhagic expansion of the intra-atrial component of WT, immediately after commencement of chemotherapy, an uncommon incident.
Israels T, Moreira C, Scanlan T, et al.SIOP PODC: clinical guidelines for the management of children with Wilms tumour in a low income setting.
Pediatr Blood Cancer. 2013; 60(1):5-11 [PubMed
Wilms tumour is a relatively common and curable paediatric tumour. Known challenges to cure in low income countries are late presentation with advanced disease, malnutrition, failure to complete treatment and limited facilities. In this article, management recommendations are given for a low income setting where only the minimal requirements for treatment with curative intent are available (setting 1). These include general management, supportive care, social support and registration of patients. Recommendations specific for Wilms tumour care include diagnostic procedures with emphasis on the role of ultrasonography, preoperative chemotherapy with a reduced dosage for malnourished children and postoperative chemotherapy based on surgical staging.
Senanayake U, Koller K, Pichler M, et al.The pluripotent renal stem cell regulator SIX2 is activated in renal neoplasms and influences cellular proliferation and migration.
Hum Pathol. 2013; 44(3):336-45 [PubMed
Embryonal renal mesenchyme contains pluripotent progenitor cells characterized by expression of SIX2, which suppresses cellular differentiation. Additionally hypomethylation of the promotor region in renal neoplasms indicates a role of SIX2 in tumorigenesis. This study focuses therefore on the investigation of SIX2 in different renal neoplasms and the mode and consequences of SIX2 activation. Expression of SIX2 was determined in renal cell carcinomas, nephroblastomas, and dysplastic kidneys using immunohistochemistry and quantitative real-time polymerase chain reaction. Its potential mode of activation was assessed by measuring upstream activators by quantitative real-time polymerase chain reaction and the level of methylation of the promoter region by quantitative DNA methylation analysis. Consequences of SIX2 activation were investigated by overexpressing SIX2 in a cell line. Forty-seven of 49 renal clear cell carcinomas showed nuclear staining of SIX2, whereas all papillary carcinomas were negative. In nephroblastomas of various subtypes blastema showed a significant up-regulation (P < .01) and a strong nuclear protein expression of SIX2 in contrast to negative epithelial and mesenchymal areas. 11 cases of dysplastic kidneys were entirely negative. Upstream activators of SIX2 indicated an activation of the signal transduction pathway in most samples. No difference of promoter methylation status was observed between blastema and epithelial structures. A significantly higher percentage of cells in the S-phase and an increased migration were detected in the cell-line overexpressing SIX2. Our study suggests that activation of SIX2 might contribute to the pathogenesis of renal clear cell carcinomas and nephroblastomas. SIX2 also appears to be a valuable marker for minimal residual blastema contributing to the prognosis of nephroblastomas.
Ha TC, Spreafico F, Graf N, et al.An international strategy to determine the role of high dose therapy in recurrent Wilms' tumour.
Eur J Cancer. 2013; 49(1):194-210 [PubMed
PURPOSE: To review event-free (EFS) and overall survival (OS) from publications describing outcome for children with relapsed Wilms' tumour. Comparisons are made between those receiving myeloablative high dose chemotherapy with autologous stem-cell rescue (HDT) and those not (NoHDT).
MATERIALS AND METHODS: Relevant information was extracted from individual patient or summary data and 3-year EFS and OS rates established. These rates were combined in a weighted manner to derive hazard ratios (HRs).
RESULTS: Nineteen publications were identified (5 HDT, 6 NoHDT, 8 both). Pooling all studies suggested an advantage to HDT with a hazard ratio (HR) for EFS of 0.87 (95% confidence interval (CI) 0.67-1.12) and 0.94 (0.71-1.24) for OS. A stratified analysis confined to studies that provided individual patient data on both HDT and NoHDT gave HRs of 0.83 (0.56-1.24) and 0.92 (0.59-1.41). Further, analyses of risk groups, defined by treatment and/or histology prior to first relapse, suggested a HR for EFS of 0.90 (95% CI 0.62-1.31) for those of high and 0.50 (CI 0.31-0.82) for the very high risk patients.
CONCLUSION: The evidence suggests, although there are many caveats since the information summarised here is not from randomised trials, a great deal of uncertainty concerning the role of HDT in patients following relapse after treatment for their Wilms' tumour. For each risk group we propose a randomised trial comparing a standard with a more intensive therapy with specific choice of regimen tailored to the risk group (and co-operative groups) concerned. A synthesis of updated evidence from studies in this overview together with any emerging studies and future trial information will form the basis for future evidence-based clinical decision-making.
Gadd S, Huff V, Huang CC, et al.Clinically relevant subsets identified by gene expression patterns support a revised ontogenic model of Wilms tumor: a Children's Oncology Group Study.
Neoplasia. 2012; 14(8):742-56 [PubMed
] Article available free on PMC
Wilms tumors (WT) have provided broad insights into the interface between development and tumorigenesis. Further understanding is confounded by their genetic, histologic, and clinical heterogeneity, the basis of which remains largely unknown. We evaluated 224 WT for global gene expression patterns; WT1, CTNNB1, and WTX mutation; and 11p15 copy number and methylation patterns. Five subsets were identified showing distinct differences in their pathologic and clinical features: these findings were validated in 100 additional WT. The gene expression pattern of each subset was compared with published gene expression profiles during normal renal development. A novel subset of epithelial WT in infants lacked WT1, CTNNB1, and WTX mutations and nephrogenic rests and displayed a gene expression pattern of the postinduction nephron, and none recurred. Three subsets were characterized by a low expression of WT1 and intralobar nephrogenic rests. These differed in their frequency of WT1 and CTNNB1 mutations, in their age, in their relapse rate, and in their expression similarities with the intermediate mesoderm versus the metanephric mesenchyme. The largest subset was characterized by biallelic methylation of the imprint control region 1, a gene expression profile of the metanephric mesenchyme, and both interlunar and perilobar nephrogenic rests. These data provide a biologic explanation for the clinical and pathologic heterogeneity seen within WT and enable the future development of subset-specific therapeutic strategies. Further, these data support a revision of the current model of WT ontogeny, which allows for an interplay between the type of initiating event and the developmental stage in which it occurs.
Kajbafzadeh AM, Harsini S, Baghayee A, Javan-Farazmand NWilms tumor and a duplex collecting system: a case report and review of literature.
J Pediatr Hematol Oncol. 2013; 35(3):e109-11 [PubMed
Wilms tumor (WT) is described as a component of many different clinical conditions and genetic syndromes. However, the simultaneous occurrence of WT and a duplex collecting system is extremely rare. We report a case of a 4-year-old boy diagnosed with WT and a left duplex collecting system. The patient underwent a left radical nephrectomy. The histologic examination diagnosed it to be a case of WT with favorable histology. The patient received the chemotherapy regimen for stage 1 WT and was in complete remission during the follow-up period of 2 years. Further investigations are required for assessing the need for screening of WT in children with genitourinary malformations.
Verschuur A, Van Tinteren H, Graf N, et al.Treatment of pulmonary metastases in children with stage IV nephroblastoma with risk-based use of pulmonary radiotherapy.
J Clin Oncol. 2012; 30(28):3533-9 [PubMed
PURPOSE: The purpose of this study was to determine the outcome of children with nephroblastoma and pulmonary metastases (PM) treated according to International Society of Pediatric Oncology (SIOP) 93-01 recommendations using pulmonary radiotherapy (RT) in selected patients.
PATIENTS AND METHODS: Patients (6 months to 18 years) were treated with preoperative chemotherapy consisting of 6 weeks of vincristine, dactinomycin, and epirubicin or doxorubicin. If pulmonary complete remission (CR) was not obtained, metastasectomy was considered. Patients in CR received three-drug postoperative chemotherapy, whereas patients not in CR were switched to a high-risk (HR) regimen with an assessment at week 11. If CR was not obtained, pulmonary RT was mandatory.
RESULTS: Two hundred thirty-four of 1,770 patients had PM. Patients with PM were older (P < .001) and had larger tumor volumes compared with nonmetastatic patients (P < .001). Eighty-four percent of patients were in CR postoperatively, with 17% requiring metastasectomy. Thirty-five patients (16%) had multiple inoperable PM and required the HR protocol. Only 14% of patients received pulmonary RT during first-line treatment. For patients with PM, 5-year event-free survival rate was 73% (95% CI, 68% to 79%), and 5-year overall survival (OS) rate was 82% (95% CI, 77% to 88%). Five-year OS was similar for patients with local stage I and II disease (92% and 90%, respectively) but lower for patients with local stage III disease (68%; P < .001). Patients in CR after chemotherapy only and patients in CR after chemotherapy and metastasectomy had a better outcome than patients with multiple unresectable PM (5-year OS, 88%, 92%, and 48%, respectively; P < .001).
CONCLUSION: Following the SIOP protocol, pulmonary RT can be omitted for a majority of patients with PM and results in a relatively good outcome.
Lubahn JD, Cost NG, Kwon J, et al.Correlation between preoperative staging computerized tomography and pathological findings after nodal sampling in children with Wilms tumor.
J Urol. 2012; 188(4 Suppl):1500-4 [PubMed
PURPOSE: Guidelines for staging Wilms tumor mandate regional lymph node sampling at nephrectomy. However, the usefulness of preoperative computerized tomography in staging lymph nodes has not been rigorously investigated. Thus, we correlated preoperative computerized tomography and pathological lymph node findings to establish a radiological criterion for pathological lymph node enlargement.
MATERIALS AND METHODS: We reviewed the medical records of children with Wilms tumor at our institution who underwent pre-chemotherapy surgery with lymph node sampling and had preoperative computerized tomography with contrast medium available for interpretation. Computerized tomography was independently reviewed by 2 radiologists blinded to the pathological findings. We collected data on the diameter of the largest regional lymph node identified and this measurement was correlated with the pathological results.
RESULTS: A total of 52 children (25 male, 27 female) with a median age of 3.1 years (range 0.4 to 9.6) were identified. The median largest regional lymph node diameter was 6 mm (range 2 to 15). Of the children 10 (19.2%) had metastatic involvement of sampled lymph nodes. A radiological cutoff of 7 mm for lymph node positivity corresponded to a negative predictive value of 89.0%, a sensitivity of 70.0% and a specificity of 57.1%. A ROC curve was constructed with these data describing the prognostic ability of the diameter of the largest regional lymph node on preoperative computerized tomography to determine lymph node positivity in Wilms tumor, which revealed an AUC of 0.67 (95% CI 0.48-0.87, p = 0.09).
CONCLUSIONS: By defining a radiological size cutoff for suspicious lymph nodes, preoperative computerized tomography for staging lymph nodes in Wilms tumor demonstrates potential clinical usefulness through risk stratification for therapy and future study design.
Cost NG, Lubahn JD, Granberg CF, et al.Pathological review of Wilms tumor nephrectomy specimens and potential implications for nephron sparing surgery in Wilms tumor.
J Urol. 2012; 188(4 Suppl):1506-10 [PubMed
PURPOSE: Nephron sparing surgery is accepted as standard of care for children with bilateral Wilms tumor or Wilms tumor in a solitary kidney and some study protocols allow nephron sparing surgery in select cases of unilateral Wilms tumor. With the increasing use of nephron sparing surgery in Wilms tumor, we reviewed pathological features from Wilms tumor radical nephrectomy specimens to determine the potential efficacy of a nephron sparing approach.
MATERIALS AND METHODS: Medical records of children undergoing pre-chemotherapy radical nephrectomy for unilateral Wilms tumor at our institution were reviewed. Ideal candidates for nephron sparing surgery were defined as those having a unifocal mass outside the renal hilum, sparing a third or more of the kidney, favorable histology, no signs of renal sinus or segmental vascular invasion, no metastatic lymph nodes or gross regional disease, and a distinct interface on pathological review between tumor and remaining parenchyma.
RESULTS: A total of 78 children at a median age of 3.2 years (range 0.3 to 16.2) underwent pre-chemotherapy radical nephrectomy for unilateral Wilms tumor. Median tumor diameter was 11 cm (range 2.5 to 22). Of these children 36 (46.2%) had tumors sparing a third or more of the kidney and 70 (89.7%) had unifocal tumors. There were 73 specimens (94.6%) that showed favorable histology, and 56 (71.8%) of the specimens had a distinct border between tumor and remaining parenchyma. In total, 19 (24.4%) of the patients reviewed met all of our strict pathological criteria as ideal partial nephrectomy candidates.
CONCLUSIONS: In a post hoc analysis using strict pathological criteria and accepted surgical oncologic principles, as many as 1 in 4 children undergoing pre-chemotherapy surgery for nonmetastatic, unilateral Wilms tumor have post-resection pathological tumor characteristics favorable for nephron sparing surgery.
Romão RL, Pippi Salle JL, Shuman C, et al.Nephron sparing surgery for unilateral Wilms tumor in children with predisposing syndromes: single center experience over 10 years.
J Urol. 2012; 188(4 Suppl):1493-8 [PubMed
PURPOSE: Unilateral Wilms tumors associated with predisposing syndromes are treated with preoperative chemotherapy followed by surgical resection. We describe our experience with nephron sparing surgery for Wilms tumor in this population at risk for metachronous lesions.
MATERIALS AND METHODS: We conducted a retrospective review of all children with a predisposing syndrome who underwent nephrectomy for malignancy during a 10-year period (2000 to 2010). Data collected included age, mode of detection, tumor size, treatment, pathology results, followup time and recurrence episodes.
RESULTS: From 2000 to 2010, 13 of 75 (19%) patients treated for Wilms tumor were diagnosed with predisposing syndrome(s). Eight patients with unilateral tumors were treated and had a mean age at diagnosis of 27 months (range 7 months to 9 years). Beckwith-Wiedemann syndrome, isolated hemihyperplasia, WAGR (Wilms tumor, Aniridia, Genitourinary abnormalities, mental Retardation) syndrome and isolated 11p13 deletion were the underlying diagnoses in 3, 2, 2 and 1 patient, respectively. All but 2 patients were diagnosed by screening ultrasound and 5 underwent preoperative chemotherapy. Median tumor size at surgery was 2.5 cm (range 1 to 13). Nephron sparing surgery was performed in 6 of 8 patients. Pathological study showed favorable histology Wilms tumor and nephrogenic rests in 6 and 2 patients, respectively. After a mean followup of 36 months (range 6 to 72) no recurrences were documented and all children had normal creatinine levels.
CONCLUSIONS: Nephron sparing surgery appears safe for patients with unilateral Wilms tumor associated with predisposing syndrome(s), allowing for the preservation of renal function and good oncologic outcomes for the available followup time. If more studies confirm our observation, current recommendations for the surgical treatment of Wilms tumor may need to reemphasize the value of attempting nephron sparing surgery in this patient population.
Gordetsky J, Katzman P, Rashid HJuxtarenal Wilms tumor in an adolescent.
Urology. 2012; 80(4):922-4 [PubMed
A 17-year-old boy presented for evaluation of an abdominal mass. Imaging revealed a 12.5-cm left upper pole renal mass. Biopsy demonstrated a malignant neoplasm consistent with blastemal-type Wilms tumor. The patient received neoadjuvant chemotherapy followed by laparoscopic radical nephrectomy. Examination revealed an unremarkable kidney uninvolved by tumor abutted by a 7.3 cm encapsulated mass. Histology revealed a triphasic Wilms tumor (nephroblastoma) with favorable histology. This tumor was classified as a juxtarenal Wilms tumor, a rare form of extrarenal Wilms tumor, with only 7 cases described in the literature. We present the first case of a juxtarenal Wilms tumor described in an adolescent.
McDonald K, Duffy P, Chowdhury T, McHugh KAdded value of abdominal cross-sectional imaging (CT or MRI) in staging of Wilms' tumours.
Clin Radiol. 2013; 68(1):16-20 [PubMed
AIM: To assess the added information gained from computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen over abdominal ultrasound in children undergoing staging of Wilms' tumours.
MATERIALS AND METHOD: Fifty-two consecutive patients with histologically proven Wilms' tumours were identified. Each had an initial staging abdominal ultrasound followed by either a CT or MRI examination of the abdomen. Details including tumour size, site, and characteristics, presence of lymph nodes, local invasion, evidence of nephroblastomatosis, and any other relevant finding were gathered from the report of each ultrasound and CT or MRI. Each CT/MRI was then re-reviewed by a consultant paediatric radiologist and a paediatric radiology fellow. The difference in findings between the ultrasound and cross-sectional imaging were noted.
RESULTS: Twelve patients were excluded from the study because the CT/MRI was performed before the ultrasound, or imaging was incomplete. Twenty-six patients were female, 14 male. The ages ranged from 9 months to 10.8 years (mean 3.75 years). Twenty-one patients out of the remaining 40 had additional findings detected on the CT or MRI examination that had not been reported on the ultrasound. The most important additional findings included three patients with nephroblastomatosis and two with contralateral tumours. Other findings included two patients with tumour haemorrhage, four with abdominal lymph node enlargement, three with inferior vena cava (IVC)/renal vein thrombus, four with adjacent organ invasion, one patient where the origin of the abdominal tumour was confirmed as renal, and one patient where possible liver invasion was excluded.
CONCLUSION: In over half the patients, CT or MRI added additional information in the local staging of Wilms' tumours. Sole reliance on ultrasound for Wilms' staging risks missing significant abnormalities.
Hakan N, Aydin M, Erdogan O, et al.A novel WT1 gene mutation in a newborn infant diagnosed with Denys-Drash syndrome.
Genet Couns. 2012; 23(2):255-61 [PubMed
Denys-Drash syndrome (DDS) is a rare disorder characterized by glomerulopathy, genital abnormalities and predisposition to Wilms' tumor. It is associated with constitutional Wilms'tumor suppressor 1 (WT1) gene mutations, in which the majority being missense mutations in the zinc-finger region. Here, we present a newborn with DDS, associated with a novel heterozygous missense mutation, p.Asp396His, on exon 9 of WT1.
Ozaki S, Takigawa N, Ichihara E, et al.Favorable response of heavily treated Wilms' tumor to paclitaxel and carboplatin.
Onkologie. 2012; 35(5):283-6 [PubMed
BACKGROUND: Heavily treated Wilms' tumor responding to the combination of paclitaxel and carboplatin has not yet been reported.
CASE REPORT: A 17-year-old man presented with hematuria. He received a diagnosis of Wilms' tumor with multiple lung metastases and was treated with preoperative chemotherapy including vincristine, dactinomycin, and doxorubicin, a right nephrectomy, and adjuvant chemotherapy, followed by pulmonary metastasectomy. During the next 8 years, he suffered from 4 relapses and has been treated with multiple anticancer agents including high-dose chemotherapy with autologous peripheral blood stem cell transplantation. Finally, the disease progressed due to peritoneal and pleural metastases. With opioid administration for left shoulder pain due to pleural metastasis, he received combination chemotherapy with carboplatin (area under the curve = 4) and paclitaxel (175 mg/m(2)) on day 1. After 2 cycles, he achieved a partial response with mild toxicity. He received 7 cycles of the chemotherapy and the time to progression was 200 days.
CONCLUSION: In a refractory case after intensive treatments, we succeeded to control the disease for a while.
Radojevic-Skodric S, Basta-Jovanovic G, Brasanac D, et al.Survivin gene promoter -31 G/C polymorphism is associated with Wilms tumor susceptibility in Serbian children.
J Pediatr Hematol Oncol. 2012; 34(8):e310-4 [PubMed
Survivin, an apoptotic inhibitor, is overexpressed in various types of cancer. Mechanisms of survivin upregulation are still poorly understood, but single nucleotide polymorphisms in the survivin gene promoter have been shown to modulate survivin expression and consequently the risk for some types of cancer. The aim of the present study was to investigate whether survivin promoter -31 G/C and -241 C/T polymorphisms could represent susceptibility factors for Wilms tumor (WT) development in Serbian population. Genotype and allele frequencies for the 2 polymorphisms in survivin promoter have been analyzed by polymerase chain reaction/restriction fragment length polymorphism in 59 WT patients and 82 controls. The frequencies of alleles and genotypes were significantly different between patients and controls for the -31 G/C polymorphism. Individuals with CC and CG genotypes had significantly decreased risk of WT compared with GG individuals (odds ratio 0.26, 95% confidence interval, 0.07-0.96; odds ratio 0.30, 95% confidence interval, 0.15-0.60). There was also a statistically significant difference in genotype frequencies between intermediate and high-risk prognostic groups (P=0.015). The -241 C/T polymorphism did not show association with WT susceptibility. Our findings suggest that the G allele at -31 survivin gene promoter position is associated with a significantly higher cancer risk in Serbian children, with a gene dosage effect.
Lorenzo AJGeintourinary malignancies in children: editorial comment.
Pediatr Clin North Am. 2012; 59(4):961-4 [PubMed
The modern management of pediatric genitourinary malignancies has resulted in survival rates that are dramatically better than figures from just a few decades ago. This is largely due to advances in multimodal treatment, collaborative efforts, and multidisciplinary management. Nevertheless, issues related to long-term side effects, treatment-related morbidity, and progression or recurrences remain important and pressing in terms of research directions and areas for improvement. In this Editorial Comment the author attempts to employ the current state of the art, masterfully summarized in the accompanying review by Drs Grimsby and Ritchey, to provide a view of trends that are likely to become increasingly important in the future, highlighting common patterns in treatment philosophy seen in other areas of oncology: more selective or patient-tailored treatment strategies, refined protocols and -whenever possible- tissue sparing and minimally invasive surgical interventions.
Grimsby GM, Ritchey MLPediatric urologic oncology.
Pediatr Clin North Am. 2012; 59(4):947-59 [PubMed
This article reviews common pediatric urologic cancers involving the genitourinary system. Rhabdomyosarcoma may occur in the bladder, prostate, paratesticular regions, vagina, or uterus. Some of these locations, such as the paratesticular region, have a more favorable outcome. Benign neoplasms account for the majority of pediatric testicular tumors and most are managed with testis-sparing surgery. Most genitourinary malignancies are expected to have a good outcome. One focus of treatment is organ preservation but not at the expense of a good oncologic outcome. Late sequelae of anticancer therapy are a concern and every attempt is made to decrease the intensity of tumor treatment.
This page last updated: 11th May 2013
Displaying links verified within last 2 weeks at time of update.