Synchronous Bilateral Wilms Tumor Research Articles

Response of bilateral Wilms tumor to chemotherapy suggests histologic subtype and guides treatment.

Patients with bilateral Wilms tumor initially receive neoadjuvant chemotherapy to shrink the tumors and increase the likelihood of successful nephron-sparing surgery. Biopsy of poorly responding tumors is often done to better understand therapy resistance. The purpose of this retrospective, single-institution study was to determine whether initial chemotherapy response is associated with tumor histology, potentially obviating the need for biopsy or change in chemotherapy. Patients with synchronous bilateral Wilms tumors who underwent surgery at St Jude Children's Research Hospital from January 2000 to March 2022 were considered for this study. A mixed-effects logistic regression model was used to evaluate the likelihood of the tumor being stromal predominant, as predicted by tumor response to neoadjuvant chemotherapy. A total of 68 patients were eligible for this study. Tumors that increased in size had an odds ratio of 19.5 (95% confidence interval [CI] = 2.46 to 155.03) for being stromal predominant vs any other histologic subtype. Age at diagnosis was youngest in patients with stromal-predominant tumors, with a mean age of 18.8 (14.1) months compared with all other histologic subtypes (χ2 = 7.05, P = .07). The predictive value of a tumor growing combined with patient aged younger than 18 months for confirming stromal-predominant histology was 85.7% (95% CI = 57.18% to 93.5%). Tumors that increased in size during neoadjuvant chemotherapy were most frequently stromal-predominant bilateral Wilms tumor, especially in younger patients. Therefore, nephron-sparing surgery, rather than biopsy, or extension or intensification of neoadjuvant chemotherapy, should be considered for bilateral Wilms tumors that increase in volume during neoadjuvant chemotherapy, particularly in patients aged younger than 18 months.

Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children’s Oncology Group AREN18B5-Q

Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of multiple tissue types for diagnosis. Of 99 total tumor specimens, 16 (16.1%) have 11p15.5 normal retention of imprinting, 25 (25.2%) have 11p15.5 copy neutral loss of heterozygosity, and 58 (58.6%) have 11p15.5 H19/ICR1 epigenetic hypermethylation (loss of imprinting). Here, we ascertain the epigenetic and genetic modes of bilateral Wilms tumor predisposition.

Nephron-sparing surgery for Wilms tumor.

The algorithm that has been used successfully in the surgical management of unilateral Wilms tumor, radical nephroureterectomy, cannot be used in children who present with synchronous bilateral renal masses. Instead, a surgical approach that removes all tumor masses while preserving as much normal renal parenchyma as possible is encouraged to avoid acute and long-term renal insufficiency. We will review technical aspects of the conduct of nephron-sparing surgery for synchronous bilateral Wilms tumor, including the more recent advances in the use of imaging adjuncts such as pre-operative 3D imaging and fluorescence-guided surgery. The potential role of nephron-sparing surgery for unilateral Wilms tumor will also be discussed.

The pathophysiology of bilateral and multifocal Wilms tumors: What we can learn from the study of predisposition syndromes.

Approximately 5% of patients with Wilms tumor present with synchronous bilateral disease. The development of synchronous bilateral Wilms tumor (BWT) is highly suggestive of a genetic or epigenetic predisposition. Patients with known germline predisposition to Wilms tumor (WT1 variants, Beckwith Wiedemann spectrum, TRIM28 variants) have a higher incidence of BWT. This Children's Oncology Group (COG)-International Society for Pediatric Oncology (SIOP-) HARMONICA initiative review for pediatric renal tumors details germline genetic and epigenetic predisposition to BWT development, with an emphasis on alterations in 11p15.5 (ICR1 gain of methylation, paternal uniparental disomy, and postzygotic somatic mosaicism), WT1, TRIM28, and REST. Molecular mechanisms that result in BWT are often also present in multifocal Wilms tumor (multiple separate tumors in one or both kidneys). We identify priority areas for international collaborative research to better understand how predisposing genetic or epigenetic factors associate with response to neoadjuvant chemotherapy, oncologic outcomes, and long-term renal function outcomes.

Evaluation of Nephron-Sparing Surgery as Potential Risk Factor for Relapse in Unilateral Wilms Tumor

BackgroundThe aim of the study was to assess the prognostic significance of nephron-sparing surgery (NSS) without tumor size limits as a risk factor for relapse in children with unilateral Wilms Tumor (WT). MethodsA 28-y retrospective single-center review was performed. Prognostic relevance of age, gender, stage, histology, nephrectomy (N), and NSS was analyzed. ResultsSixty-nine cases (42 females and 27 males) with WT, off-therapy from 21 to 325 mo after chemotherapy mainly based on the International Society of Pediatric Oncology trials, were treated at our institution. Five cases were excluded (three children with synchronous bilateral WT and two adults with unilateral WT). Of 64 children with unilateral WT, 51 underwent N and 13 NSS without tumor size limits. Indeed, two-thirds of children who underwent NSS presented with a tumor diameter >4 cm. Overall, nine patients (14%) had a relapse (male-to-female ratio = 1:8). Initial surgery was N in eight cases and NSS in another one. Relapse rates in N and NSS groups were 15.7% and 7.7% (P = nonsignificant), respectively; the relapse rates in N and NSS groups were 8.6% and 7.7% (P = nonsignificant) for stages I-II unilateral WT cohort, respectively. On univariate analysis, factors correlated with probability of relapse were unfavorable histology (P < 0.002) and stage III disease (P < 0.01). ConclusionsIn unilateral WT, NSS, whenever feasible, does not seem to increase the risk of recurrence. A multicenter prospective trial is required to carefully evaluate this risk.

Absence of the TRIP13 c.1060C>T Mutation in Wilms Tumor Patients From Pakistan.

Wilms tumor (WT) is the most common childhood malignant renal tumor. Germline mutations in several WT predisposition genes have been identified. However, the fundamental cause of most WT patients remains unexplained. Recently, a founder mutation, c.1060C>T (p. Arg254X) in a mitotic spindle checkpoint gene, TRIP13, was reported in 5 unrelated children with WT from the United Kingdom, of Pakistani descent from Azad Kashmir region. This observation suggests other children with WT in Pakistan may also harbor this mutation. We conducted the first study to assess the contribution of TRIP13 c.1060C>T mutation to WT in Pakistan. Constitutional genomic DNA from 68 Pakistani individuals including unrelated WT cases (n=26) and one (n=10) or both (n=32) of their parent(s) were screened for the TRIP13 c.1060C>T mutation using DNA sequence analysis. We also included positive controls in the analyses. The median age of WT diagnosis was 3.0 years (range, 0.75 to 10). The TRIP13 c.1060C>T mutation was not found in any WT patient (n=26) or their parents (n=42). Twenty-four patients (92.4%) presented with unilateral tumor and 2 patients (7.7%) were diagnosed with synchronous bilateral WT. Thirteen patients (50%) reported parental consanguinity. Thirteen patients (50.0%) belonged to the Punjabi ethnicity and 1 patient (3.8%) had a Kashmiri background. Four patients (16.7%) reported a family history of WT or other malignancies. The predominant histologic subtype was stromal (46.2%). The majority of patients presented with >5 cm of tumor size (81%). None of the patients had a personal or family history of congenital anomalies, or associated genetic syndromes. Our findings suggest that TRIP13 c.1060C>T mutation may be infrequent in Pakistani WT cases. Further evaluation of this mutation in a large number of WT patients of Kashmiri heritage and various ethnic backgrounds from Pakistan is warranted.

Synchronous Bilateral Wilms Tumor: Five-Year Single-Center Experience with Assessment of Quality of Life.

Context:Synchronous Bilateral Wilms tumor (sBWT).Aims:This study aimed to assess the outcome of patients with sBWT treated on SIOP protocol.Settings and Design:Retrospective and prospective randomized study.Subjects and Methods:SIOP 93-01 protocol was used to study nine patients of sBWT in a single center and followed up over a period from 2 to 5 years.Statistical Analysis Used:Unpaired t-test and Mann–Whitney U-test were used for analysis.Results:Of nine patients, six were included in the study as three patients lost to follow-up. Among the six patients, there were four girls and two boys with a median age of 2 years. Mean regression in the size of tumor was 87% in four out of six patients. Tumor with unfavorable histology showed 32% response (ratio of favorable: unfavorable histology 2:1). Event-free survival rate was 81.3% and overall survival was 90% over 2–5 years. Recurrence was seen in two patients of whom one had Denys–Drash syndrome. Mean DTPA glomerular filtration rate was 91.4/ml/min/1.73 m2 preoperatively and that of 3 months after completion of treatment was 84/ml/min/1.73 m2. Health-related quality of life (HRQOL) using Pediatric Quality of Life Inventory and Lansky Play Performance Scale revealed significant improvement results of all functioning domains such as physical, social, emotional, and school subscales with P < 0.05 and performance scale (P < 0.04).Conclusions:We suggest SIOP protocol for sBWT and bilateral nephron-sparing surgery in two stages. However, long-term follow-up is required to assess the ultimate renal function outcome. HRQOL is an essential guide in improving the conditions of pediatric cancer survivors.

Bilateral Wilms tumors: Treatment results from a single center.

Aydın B, Akyüz C, Yalçın B, Ekinci S, Oğuz B, Akçören Z, Yıldız F, Varan A, Kurucu N, Büyükpamukçu M, Kutluk T. Bilateral Wilms tumors: Treatment results from a single center. Turk J Pediatr 2019; 61: 44-51. The management of bilateral Wilms tumor (BWT) is challenging, particularly due to its presentation at a younger age, rarity, and difficulty for treatment decisions and surgical evaluation comparing to unilateral WT. In this study, the outcome of BWT patients from a single center who were treated by the Turkish Pediatric Oncology Group (TPOG) Wilms Tumor Regimen were retrospectively reviewed. From 1990 to 2016, 30 patients with synchronous BWT were treated with a preoperative chemotherapy of vincristine and actinomycin-D (VA). Chemotherapy was continued until safe nephron sparing surgery (NSS) could be performed for as long as radiological tumor response continued; otherwise, the chemotherapy was intensified by adding doxorubicin (D) alternating with VA every 6 weeks. The median followup of patients was 59 months (4-297 months). The median duration of preoperative chemotherapy was 81 days and ranged between 14 days and 198 days. Preoperative chemotherapy was modified in seven patients (23%) to the VAD regimen. Twenty-two patients (73%) had a radical nephrectomy on the larger tumor and NSS on the contralateral kidney, and 6 patients (20%) had bilateral NSS. Postoperative tumor stages for stage I, II and III were 60%, 22% and 14%, respectively. The 5-year event free survival (EFS) rates were 100%, 90% and 51% for stages I, II and III (p=0.02), respectively. Unfavorable histology and nephrogenic rests were reported in 20% and 20% of patients, respectively. The 5-year overall survival (OS) and EFS rates were 50% and 25%, respectively, in patients with anaplasia, while the same rates were 96% and 96% in patients with favorable histology tumors (p=0.05 and p < 0.001). The 10-year EFS and OS rates for all patients were 82% and 86%, respectively. Our results are comparable with the literature. VA is effective as initial preoperative treatment of BWT and allows for safe resection.

Tumor de Wilms Bilateral Sincrônico: Avaliação Cirúrgica e Sobrevida

Introdução: Os tumores renais representam cerca de 7% de todas as neoplasias malignas da infância. O tumor de Wilms bilateral sincrônico corresponde a 5-7% de todos os nefroblastomas. O tratamento consiste em quimioterapia pré-operatória, seguida de cirurgia conservadora, quimioterapia pós-operatória e, quando indicada, radioterapia. Objetivo: Analisar o tipo de cirurgia e a sobrevida global dos pacientes com tumor de Wilms bilateral sincrônico. Método: Este estudo de coorte retrospectivo incluiu 18 pacientes pediátricos do Hospital do Câncer I, do Instituto Nacional de Câncer José Alencar Gomes da Silva, no Rio de Janeiro, de janeiro de 2000 a dezembro de 2017. Curvas de sobrevida foram calculadas pelo método Kaplan-Meier. Resultados: A idade mediana ao diagnóstico foi de 19 meses, sendo dez casos do sexo feminino. Em 62,5% dos rins operados, foi possível realizar cirurgia conservadora e, em 41,2% (7/17) dos pacientes, em ambos os rins. A sobrevida global em cinco anos, segundo o tipo cirurgia, foi de 87,5% para cirurgia conservadora e de 62,8% para nefrectomia total (p=0,0001). A sobrevida global em cinco anos para a coorte inteira foi de 70,8%. Conclusão: A cirurgia preservadora de tecido renal em crianças com o tumor de Wilms bilateral sincrônico é viável e pode ser realizada com segurança em centros de referência.

Coexistence of synchronous bilateral Wilms tumor and trisomy 21 – first report and review of literature

Coexistence of synchronous bilateral Wilms tumor and trisomy 21 – first report and review of literature

Familial synchronous bilateral teratoid Wilms tumor with elevated alpha-fetoprotein level.

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.

Comprehensive renal function evaluation in patients treated for synchronous bilateral Wilms tumor

ObjectivesThe purpose of this study was to perform a comprehensive assessment of long-term renal function in patients treated at our institution for synchronous bilateral Wilms tumor (BWT) and to determine the optimal method for estimating glomerular filtration rate (eGFR). MethodsSurgical approach, adjuvant therapy, and pathology reports were reviewed for patients with at least six months follow-up from definitive surgery. eGFRs, as assessed by the Schwartz and Chronic Kidney Disease in Children (CKiD) formulas, were compared to measured GFR (mGFR) determined by 99mTc-DTPA scanning. Urine studies, including microalbumin, β-microglobulin, and FENa were also reviewed. ResultsForty-two patients were identified. Of 36 living patients, 28 (77.8%) had greater than 6months follow-up, with a median overall follow-up of 5.2years (range: 1.4–13.4). The median mGFR was 97mL/min/1.73m2, while the median eGFRSchwartz and eGFRCKiD were 103.3mL/min/1.73m2 and 79.7mL/min/1.73m2, respectively, (p=0.13 and p=0.75, compared to mGFR). Eleven (39.3%) patients had at least one abnormal urine study (microalbumin >30μg/g creatinine, n=3; β-2 microglobulin >133μg/g creatinine, n=9; FENa>1%, n=4). ConclusionsIn our series, few patients had an abnormally low GFR. Neither method for estimating GFR gave a significantly different result from measured GFR, suggesting that the Schwartz equation is adequate, although specific urine tests may be more sensitive for detecting subtle renal dysfunction. Level of evidenceLevel IV — retrospective case series with no comparison group.

Bilateral Wilms tumors treated according to the Japan Wilms Tumor Study Group protocol

The introduction of multimodal therapy has improved the survival rate of bilateral Wilms tumors (BWT); however, the results are still not satisfactory in terms of the renal preservation. To establish a new treatment strategy for BWT, we reviewed the results of the cases registered in the Japan Wilms Tumor Study Group (JWiTS). This analysis concerned patients with synchronous BWT registered in the JWiTS between 1996 and 2011. In these patients, the management of BWT included initial tumor resection or biopsy followed by chemotherapy. The details of the treatments and outcomes were analyzed. Among the 355 cases registered in the JWiTS database, 31 (8.7%) had BWT. They were 16 males and 15 females with a mean age of 15.5 months. Preoperative chemotherapy was performed in 24 cases. Bilateral nephron-sparing surgery (NSS) was achieved in 10 of 28 cases (36%). All of the cases were of favorable nephroblastoma without anaplasia, and a WT1 mutation was detected in 21 of the 27 cases (78%) examined. The 5-year overall survival was 92.6%; however, 10 children (40%) developed impaired renal function and three of them developed renal failure. The long-term survival rates for patients with synchronous BWT have improved. However, more than half of patients receive nephrectomy. The protocol should be changed to improve the rate of preservation of the renal parenchyma. Preoperative chemotherapy should be performed to shrink the tumors in every case, and subsequent NSS should be carried out after a central imaging evaluation.

Synchronous bilateral Wilms tumor

The optimal management of bilateral Wilms tumor (BWT) is challenging, and their survival is lower than for unilateral tumors. This report discusses a large series of BWTs treated in Italy in the last 2 decades. This analysis concerns patients with synchronous BWT registered at Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers between 1990 and 2011; details on their treatment and outcome are presented and discussed. Ninety BWTs were registered in the AIEOP Wilms tumor database. Preoperative chemotherapy was given for a median 12 weeks before definitive tumor resection was attempted. Forty-eight percent of the patients had preservation of bilateral renal parenchyma. The proportion of bilateral nephron-sparing surgeries was not higher in the 37 patients initially given doxorubicin/vincristine/actinomycin D (32%) than in the 43 children receiving vincristine/actinomycin D alone (58%). The 4-year disease-free survival rate was 66.5% ± 5% and overall survival was 80% ± 5% for the cohort as a whole. The 4-year disease-free survival (overall survival) for 18 children with diffuse anaplasia or postchemotherapy blastemal-type tumors was 51% ± 13% (62% ± 13%), as opposed to 72% ± 3% (88% ± 4%) for 68 children with a favorable histology (log-rank P = .04 [P = .007]). These results provide further evidence that the optimal duration and choice of drugs for preoperative chemotherapy remain an open question. Outcome remained significantly worse for BWT than for unilateral Wilms tumor. To enable the conservative treatment of as many affected kidneys as possible, only centers with experience in BWT should manage such cases.

Familial synchronous bilateral teratoid Wilms tumor with elevated alpha-fetoprotein level

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.

Nephron Sparing Surgery for Unilateral Wilms Tumor in Children with Predisposing Syndromes: Single Center Experience Over 10 Years

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. 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. 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. 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.

Bilateral Wilms' tumor: Mansoura multi-centers 15 years experience

Bilateral Wilms' tumor (WT) is a challenge. Aggressive surgical resection is needed to prevent recurrence. We revised the clinico-epidemiological criteria of bilateral WT patients in our locality and relation to outcome. 462 WT patients were registered in three medical centers at Mansoura, Egypt. Twenty five patients had bilateral WT whose medical records were revised for all clinico-epidemiologic data plus treatment details, toxicity, and outcome. The mean age was 34.5 months; 64% of cases were female. Abdominal mass was the commonest presentation (72%). Congenital anomalies were reported in two cases (one case showed hemihypertrophy and the other showed aniridia). About 60% had favorable pathology. Nineteen cases had synchronous bilateral WT (76%) and the remaining (six cases) had metachronous tumors. For the synchronous cases, the response rate to preoperative chemotherapy was 79% and nephron sparing surgery for the least involved kidney was possible in all. Survival rate was 74%. Metachronous tumor management included nephrectomy followed by chemotherapy for the initially diagnosed tumors. However, nephron sparing surgery of the contralateral tumors following preoperative chemotherapy was possible in two cases and the survival rate was 33%. No renal failure or any therapy-related complications were reported. Bilateral WT is predominantly synchronous with favorable histology, with female predilection and possibly congenital anomalies. Preoperative chemotherapy followed by nephron sparing surgery has a favorable outcome with preserved renal function especially in patients with synchronous WT. Response to preoperative chemotherapy had a statistically significant prognostic impact.

Risk Factors for End Stage Renal Disease in Non- WT1-Syndromic Wilms Tumor

We assessed risk factors for end stage renal disease in patients with Wilms tumor without known WT1 related syndromes. We hypothesized that patients with characteristics suggestive of a WT1 etiology (early onset, stromal predominant histology, intralobar nephrogenic rests) would have a higher risk of end stage renal disease due to chronic renal failure. We predicted a high risk of end stage renal disease due to progressive bilateral Wilms tumor in patients with metachronous bilateral disease. End stage renal disease was ascertained in 100 of 7,950 nonsyndromic patients enrolled in a National Wilms Tumor Study during 1969 to 2002. Risk factors were evaluated with cumulative incidence curves and proportional hazard regressions. The cumulative incidence of end stage renal disease due to chronic renal failure 20 years after Wilms tumor diagnosis was 0.7%. For end stage renal disease due to progressive bilateral Wilms tumor the incidence was 4.0% at 3 years after diagnosis in patients with synchronous bilateral Wilms tumor and 19.3% in those with metachronous bilateral Wilms tumor. For end stage renal disease due to chronic renal failure stromal predominant histology had a HR of 6.4 relative to mixed (95% CI 3.4, 11.9; p<0.001), intralobar rests had a HR of 5.9 relative to no rests (95% CI 2.0, 17.3; p=0.001), and Wilms tumor diagnosis at less than 24 months had a HR of 1.7 relative to 24 to 48 months and 2.8 relative to greater than 48 months (p=0.003 for trend). Metachronous bilateral Wilms tumor is associated with high rates of end stage renal disease due to surgery for progressive Wilms tumor. Characteristics associated with a WT1 etiology markedly increased the risk of end stage renal disease due to chronic renal failure despite the low risk in non-WT1 syndromic cases overall.

Bilateral Wilms’ tumor: the need to improve outcomes

Wilms tumor (WT) is the most common primary malignant renal tumor of childhood, accounting for 6% of all pediatric tumors, and represents one of the great success stories in pediatric cancer therapy. The paradigm for the treatment of a child with WT has evolved from a primary goal of survival alone to a risk-based approach. Unfortunately, despite 35 years of clinical trials by cooperative groups, bilateral WT (BWT) patients have not been formally studied. The most recent survival, rated for patients treated on National WT Study-5 with BWT, was 61–80.8% with favorable histology and 43.8% for a child with anaplastic or unfavorable histology. This article reviews outcomes and surgical considerations in the treatment of patients with synchronous BWT and proposes possible future directions in the treatment.

Molecular evidence of the independent origin of multiple Wilms tumors in a case of WAGR syndrome

This study investigated the genetic events leading to tumorigenesis in a patient affected with WAGR syndrome who developed multiple distinct Wilms tumors (WTs). At 1 year of age, the child developed two synchronous bilateral WTs that were resected by partial nephrectomy. Histologically, these tumors were fetal rhabdomyomatous nephroblastomas. Immunohistochemical study revealed the absence of nuclear expression of WT1 protein, while beta-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular investigations of WT1 gene and exon 3 of beta-catenin (CTNNB1) gene detected no mutations. At 4 years of age, 28 months after the chemotherapy completion, a third WT was diagnosed in the left kidney, and surgically removed before any further chemotherapy. Nine months after surgery, a metastasis was detected in the left lung. Both the third renal tumor and the lung metastasis showed a blastema-predominant morphology. Immunohistochemistry confirmed the lack of expression of WT1 protein, while beta-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular analysis of the third renal tumor and the lung metastasis revealed a 4 bp deletion in exon 7 of WT1 gene, leading to a frameshift of the reading frame and to a premature stop of the translation (c.925_928delACTC, p.T309LfsX71); no mutations in the exon 3 of the beta-catenin gene were documented. These data demonstrate that multiple WTs can arise as a consequence of different genetic events in a patient with genetic predisposition, such as WAGR syndrome.