Nonsyndromic Wilms Tumor Research Articles

Kidney Function and Body Composition in Adult Survivors of Unilateral, Non-Syndromic Wilms Tumor: A Report From the St. Jude Lifetime Cohort Study.

The relationships among treatment exposures, body composition, and estimated glomerular filtration rate (eGFR) in adult survivors of Wilms tumor have not been well studied. We evaluated body composition with dual-energy x-ray absorptiometry (DXA) and eGFR with the updated Chronic Kidney Disease Epidemiology Collaboration equations (creatinine only-eGFRCr, cystatin C only-eGFRCysC, creatinine and cystatin C-eGFRCr+CysC) without race in 134 adults previously treated for unilateral, non-syndromic Wilms tumor at St. Jude Children's Research Hospital between 1964 and 2004 with chemotherapy and with (hemiabdomen [HA] or whole abdomen [WA]) or without radiation therapy (RT). Z-scores for DXA variables were calculated using data from the National Health and Nutrition Examination Survey. WART was associated with a lower relative total (p = 0.004) and trunk (p < 0.001) lean mass, eGFRCr (p = 0.008), eGFRCysC, (p < 0.001), and eGFRCr+CysC (p < 0.001), and higher values of cystatin C (p < 0.001). Linear regression demonstrated that relative total lean mass (p = 0.009) and relative trunk lean mass (p < 0.001) Z-scores, and eGFRCr (p = 0.013) were lower among those who received WART compared to No RT patients. WART is associated with lower relative total and trunk lean mass Z-scores and eGFR, regardless of the equation used, and is lower in survivors treated with WART compared to unirradiated survivors of unilateral, non-syndromic WT. Assessments using other GFR measures may provide greater insight into the mechanism and magnitude of kidney function loss among WART-treated WT survivors.

The accuracy of estimating equations for the evaluation of kidney function in adult survivors of unilateral, nonmetastatic, non-syndromic Wilms tumor: A pilot study from the St. Jude Lifetime Cohort Study.

Adult survivors of unilateral, nonmetastatic, non-syndromic Wilms tumor (WT) treated with whole abdomen radiation therapy (WART) are at risk for impaired kidney function. The impact of bias and accuracy on estimated glomerular filtration rate (eGFR) among adult survivors of WT has not been well documented. We clinically evaluated male and female WT survivors with creatinine and cystatin C, calculated eGFR using the Chronic Kidney Disease-Epidemiology equations with and without cystatin C, and measured 99mTc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. WT survivors treated with unilateral nephrectomy (UN), non-nephrotoxic chemotherapy (NNC) and WART or treated with UN, no radiation therapy, and NNC were enrolled. Correlations between 99mTc DTPA clearance and eGFR were calculated. Bias and the percentage of eGFR calculations that differed from the 99mTc DTPA clearance by 10% or less (P10) or 30% or less (P30) (accuracy) were calculated. Among female WT survivors, none of the eGFR calculations was statistically significantly correlated with 99mTc DTPA clearance. Among both unirradiated and WART-treated male WT survivors, 99mTc DTPA clearance correlated well with eGFR calculations that included creatinine. eGFR calculations that included creatinine were positively biased among female participants compared to 99mTc DTPA clearance, and no P30 was greater than 90% among either irradiated males or females. Among female survivors of unilateral, nonmetastatic, non-syndromic WT who have undergone UN, eGFR is poorly correlated with, is positively biased, and lacks sufficient accuracy, compared to 99mTc DTPA clearance.

Evaluation of kidney function and body composition in adult survivors of unilateral, non-metastatic, non-syndromic Wilms tumor: A report from the St. Jude Lifetime Cohort Study.

10064 Background: The relationships among treatment exposures, body composition and estimated glomerular filtration rate (eGFR) in adult survivors of childhood have not been well studied. Methods: We evaluated body composition with dual energy x-ray absorptiometry (DXA) and eGFR with the Kidney Disease International Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) in 149 adults previously treated for non-syndromic, non-metastatic, unilateral Wilms tumor at St. Jude Children’s Research Hospital between 1964 and 2004 with chemotherapy and with [(whole abdomen (WA) radiation therapy (RT) – 41 patients; median dose 12.5 Gray (Gy), Interquartile Range (IQR) 12.5 – 20.0 Gy); (hemiabdomen (HA) RT – 30 patients; median dose 12.0 Gy, IQR 10.8 – 20.1 Gy)] or without (78 patients) RT. z-scores for DXA variables were calculated using data from the National Health and Nutrition Survey (1). Results: The study population [56 males (37.6%), 109 whites (73.2%)] was a median of 3.1 years of age at diagnosis (IQR: 1.7-4.3) and 23.4 years at evaluation (IQR: 23.4-35.5). Relative total and relative trunk lean mass, and eGFR were significantly decreased among those who received WART compared to unirradiated patients. Linear regression demonstrated that WART was significantly associated with a lower eGFR (p = 0.012) and higher value of creatinine (p = 0.013). Conclusions: Relative total and relative trunk lean mass, and eGFR are decreased in survivors of unilateral, non-metastatic, non-syndromic WT following WART. Although eGFR was in the normal range, eGFR may be inaccurate due to loss of lean mass. Assessments using non-secreted molecules may more accurately measure the magnitude of kidney function loss among WART treated WT survivors. 1. PLoS ONE 2009;4(9):e7038. [Table: see text]

Abstract 6381: Long-term kidney function after treatment for unilateral, non-metastatic, non-syndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study

Abstract Background: We previously reported that the estimated glomerular filtration rate (eGFR) was decreased among survivors of unilateral, non-metastatic, non-syndromic Wilms tumor (WT) treated with whole abdomen radiation therapy (WART) compared to controls, but not compared to unirradiated WT survivors (Pediatr Blood Cancer 2020;67:e28271). The impact of sex on estimates of kidney function among adult survivors of WT has not been well-documented. Methods: We clinically evaluated male and female WT survivors with creatinine and cystatin C, calculated eGFR using the Chronic Kidney Disease - Epidemiology (CKD-EPI) equations with and without cystatin C and measured 99mTc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. WT survivors consisted of 20 treated with unilateral nephrectomy (UN), non-nephrotoxic chemotherapy (NNC) and whole abdomen radiation therapy (WART) (mean - 20.2 Gray (Gy); standard deviation (SD) - 9.12 Gy), and 20 treated with UN, no radiation therapy, and NNC. Correlations between 99mTc DTPA clearance and eGFR were calculated. Results: Among female WT survivors, none of the eGFR calculations was statistically significantly correlated with 99mTc DTPA clearance. Among male WT survivors, 99mTc DTPA clearance correlated well with eGFR calculations that included creatinine. Results are shown in the Table. Conclusions: Among female survivors of unilateral, non-metastatic, non-syndromic WT who have undergone UN, eGFR is poorly correlated with 99mTc DTPA clearance. Evaluation of treatment-related changes in body composition may provide insight into these results. Correlation between eGFR and 99mTc DTPA clearance Females eGFR(CKD-EPI) 99mTc DTPA clearance No radiation therapy (n=13) Whole abdomen radiation therapy(n=12) Pearson correlation coefficient p-value Pearson correlation coefficient p-value Creatinine only 0.109 0.723 -0.295 0.352 Cystatin C only 0.311 0.301 0.094 0.782 Creatinine and cystatin C 0.348 0.244 -0.028 0.935 Males No radiation therapy (n=6) Whole abdomen radiation therapy(n=6) Pearson correlation coefficient p-value Pearson correlation coefficient p-value Creatinine only 0.827 0.043 0.859 0.028 Cystatin C only 0.811 0.050 0.592 0.216 Creatinine and cystatin C 0.878 0.021 0.866 0.026 Citation Format: Daniel M. Green, Mingjuan Wang, Matthew J. Krasin, Andrew M. Davidoff, DeoKumar Srivastava, Dennis W. Jay, Kirsten K. Ness, Barry L. Shulkin, Jennifer Q. Lanctot, Kyla C. Shelton, Rachel C. Brennan, Matthew J. Ehrhardt, Stephanie Dixon, Beth A. Kurt, Leslie L. Robison, Melissa M. Hudson, Sheri L. Spunt. Long-term kidney function after treatment for unilateral, non-metastatic, non-syndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6381.

PD37-03 DOES NEOADJUVANT CHEMOTHERAPY REDUCE THE COMPLEXITY OF WILMS TUMOR? AN ANALYSIS USING THE NEPHROMETRY SCORE

You have accessJournal of UrologyCME1 Apr 2023PD37-03 DOES NEOADJUVANT CHEMOTHERAPY REDUCE THE COMPLEXITY OF WILMS TUMOR? AN ANALYSIS USING THE NEPHROMETRY SCORE Catherine Nguyen, Eric Bih, Kathleen Hosek, Michelle Dai, and Niccolo Passoni Catherine NguyenCatherine Nguyen More articles by this author , Eric BihEric Bih More articles by this author , Kathleen HosekKathleen Hosek More articles by this author , Michelle DaiMichelle Dai More articles by this author , and Niccolo PassoniNiccolo Passoni More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003335.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Per the Children’s Oncology Group (COG) protocols, partial nephrectomy (PN) for Wilms tumor (WT) is reserved for bilateral tumors or lesions in solitary kidneys. Furthermore, most WTs are large masses that would not be amenable to partial nephrectomy. Unlike COG, the Societe Internationale d’Oncologie Pediatrique (SIOP) offers neoadjuvant chemotherapy (NAC) prior to surgical resection, allowing for tumor shrinkage. The Nephrometry score (NS) is a tool that was developed to assess the complexity of renal cell carcinoma, and thus the feasibility of partial nephrectomy. It relies on morphological features of tumors seen on cross-sectional imaging. The NS was however developed for renal cell carcinoma. Only one study to date has assessed Wilms tumors using the NS, showing that most are highly complex lesions not amenable to (PN). The goal of our study is to assess if NAC decreases the complexity of Wilms tumor using the NS. METHODS: We retrospectively identified patients with WT at our institution who received NAC (according to COG protocols). Pre- and post- treatment tumor volumes and NS were calculated by a single radiologist. For bilateral or multifocal tumors, the score was calculated for the most complex mass. NS was broken down into low, intermediate and high complexity groups. Rates of PN were stratified by NS score and by pre-operative variables. Statistical differences were assessed using paired t-tests and chi square tests. RESULTS: 54 patients were identified. The median pre- and post-treatment tumor volumes were 499 and 90 cm3, respectively (p<0.0001). Before NAC, NS was considered low, intermediate and high in 3.7%, 13% and 83.3% of patients, respectively. After NAC, the NS score was low, intermediate and high in 11.1%, 25.9% and 63% of patients. Fourteen tumors (26%) had their complexity downgraded. Overall rates of PN were 35% (n=19). There were statistically significant higher rates of PN for tumors with a low NS (83%) vs intermediate (64.3%) and high (14.7%) scores (p<0.0001). Among pre-operative variables such as age, sex, race, ethnicity, syndromic Wilms and stage, only female sex was statistically associated with higher rates of downgrading after NAC (36% vs 9.5% of males, p=0.028). CONCLUSIONS: The majority of WT are complex masses. Our data shows that NAC can reduce tumor complexity in 26% of cases, with more than half the patients with low or intermediate complexity WT undergoing successful PN. Further studies are needed to identify which patients with unilateral non-syndromic WT could benefit from NAC with the goal of nephron-sparing surgery. Source of Funding: Department © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e987 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Catherine Nguyen More articles by this author Eric Bih More articles by this author Kathleen Hosek More articles by this author Michelle Dai More articles by this author Niccolo Passoni More articles by this author Expand All Advertisement PDF downloadLoading ...

Late Health Outcomes Among Survivors of Wilms Tumor Diagnosed Over Three Decades: A Report From the Childhood Cancer Survivor Study.

To evaluate long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor (WT) survivors according to conventional treatment regimens. Cumulative incidence of late mortality (≥ 5 years from diagnosis) and chronic health conditions (CHCs) were evaluated in WT survivors from the Childhood Cancer Survivor Study. Outcomes were evaluated by treatment, including nephrectomy combined with vincristine and actinomycin D (VA), VA + doxorubicin + abdominal radiotherapy (VAD + ART), VAD + ART + whole lung radiotherapy, or receipt of ≥ 4 chemotherapy agents. Among 2,008 unilateral WT survivors, 142 deaths occurred (standardized mortality ratio, 2.9, 95% CI, 2.5 to 3.5; 35-year cumulative incidence of death, 7.8%, 95% CI, 6.3 to 9.2). The 35-year cumulative incidence of any grade 3-5 CHC was 34.1% (95% CI, 30.7 to 37.5; rate ratio [RR] compared with siblings 3.0, 95% CI, 2.6 to 3.5). Survivors treated with VA alone had comparable risk for all-cause late mortality relative to the general population (standardized mortality ratio, 1.0; 95% CI, 0.5 to 1.7) and modestly increased risk for grade 3-5 CHCs compared with siblings (RR, 1.5; 95% CI, 1.1 to 2.0), but remained at increased risk for intestinal obstruction (RR, 9.4; 95% CI, 3.9 to 22.2) and kidney failure (RR, 11.9; 95% CI, 4.2 to 33.6). Magnitudes of risk for grade 3-5 CHCs, including intestinal obstruction, kidney failure, premature ovarian insufficiency, and heart failure, increased by treatment group intensity. With approximately 40% of patients with newly diagnosed WT currently treated with VA alone, the burden of late mortality/morbidity in future decades is projected to be lower than that for survivors from earlier eras. Nevertheless, the risk of late effects such as intestinal obstruction and kidney failure was elevated across all treatment groups, and there was a dose-dependent increase in risk for all grade 3-5 CHCs by treatment group intensity.

Bilateral synchronous, NON syndromic wilms tumor

Bilateral synchronous Wilms tumour represents 4–8% of all Wilms tumours (WTs). The ultimate goal in such cases is to preserve as much renal parenchyma as possible while achieving total/near total tumour resection. We report the case of a 3 years old male child presenting with bilateral synchronous Wilms tumour.

Syndromic Wilms tumor: a review of predisposing conditions, surveillance and treatment.

Predisposing syndromes associated with an increased risk of Wilms tumor (WT) are responsible for 9–17% of all cases of the malignancy. Due to an earlier age at WT diagnosis and an increased incidence of bilateral and metachronous disease, management of syndromic WT warrants a distinct approach from that of non-syndromic WT. This review of English-language manuscripts about WT focuses on the most common syndromes, surveillance protocols and current treatment strategies. Highlighted syndromes include those associated with WT1, such as WAGR (Wilms-Aniridia-Genitourinary-mental Retardation), Denys-Drash syndrome (DDS), and Frasier syndrome, 11p15 defects, such as Beckwith-Wiedemann syndrome (BWS), among others. General surveillance guidelines include screening renal or abdominal ultrasound every 3–4 months until the age of 5 or 7, depending on the syndrome. Further, some of the predisposing conditions also increase the risk of other malignancies, such as gonadoblastoma and hepatoblastoma. With promising results for nephron-sparing surgery in bilateral non-syndromic WT, there are increasing reports and recommendations to pursue nephron-sparing for these patients who are at greater risk of bilateral, metachronous lesions. In addition to the loss of renal parenchyma from malignancy, many patients are at risk of developing renal insufficiency as part of their syndrome. Although there may be some increase in the complication rate, recurrence free survival seems equivalent. Some conditions require specialized approaches to adjuvant therapy, as their syndrome may make them especially susceptible to side effects.

Long-term renal function after treatment for unilateral, nonsyndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study.

The impact of specific treatment modalities on long-term renal function and blood pressure among adult survivors of Wilms tumor (WT) has not been well documented. Among 40 WT survivors and 35 noncancer controls, we estimated the glomerular filtration rate (eGFR) using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equations with and without cystatin C, obtained 24-hour ambulatory blood pressure readings, and, among survivors only, measured 99m Tc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. Survivors were treated with unilateral nephrectomy and nonnephrotoxic chemotherapy. Twenty received whole abdomen radiation therapy (WART) [median -16.5 Gray (Gy)], and 20 received no radiation therapy. Pairwise comparisons between survivors treated with and without WART, and each group to controls were performed using two-sample t tests. Twenty-six (65%) WT survivors were female, and 33 (83%) were non-Hispanic white. GFR estimated with creatinine or creatinine + cystatin C was decreased among irradiated survivors compared with controls. No irradiated or unirradiated participant had an eGFR (creatinine + cystatin C)<60mL/min/1.73m2 . The prevalence of hypertension was significantly increased among unirradiated (25%) and irradiated survivors (35%) compared with controls (0%). Of the 24-hour ambulatory blood pressure monitoring parameters evaluated, only mean sleep period diastolic blood pressure load of those who received WART was significantly different from that of controls. Chronic kidney disease was infrequent in long-term survivors of unilateral nonsyndromic WT, whether treated with WART or no radiation. The prevalence of hypertension was increased in both groups compared with controls, emphasizing the need for ongoing monitoring of renal and cardiovascular health.

Estimated glomerular filtration rate after nephrectomy for Wilms tumor

The aim of this study was to assess long-term residual kidney function after unilateral nephrectomy for non-syndromic Wilms tumor (NSWT). Of the patients who underwent one-sided NSWT at Tohoku University Hospital between 1977 and 2003, nine were followed up until age ≥18years. For these nine patients, we retrospectively evaluated estimated glomerular filtration rate (eGFR) in childhood (3-10years old), adolescence (11-17years old) and adulthood (≥18years). Mean age at the last follow up was 23.0years. Tumor classification was as follows: stage I tumor, n=6; stage II tumor, n=3; mixed-type nephroblastoma, n=8; and congenital mesoblastic nephroma, n=1. Mean eGFR was 101.3±21.2 mL/min/1.73 m2 in childhood, 106.0±32.1 mL/min/1.73 m2 in adolescence and 100.5±20.7 mL/min/1.73 m2 in adulthood. Therefore, no significant change in eGFR was observed over the three life stages evaluated. Further, none of the patients met the diagnostic criteria for chronic kidney disease by early adulthood. eGFR after unilateral nephrectomy in patients with NSWT remained ≥60 mL/min/1.73 m2 during the transition from childhood to early adulthood, with no development of chronic kidney disease or end-stage kidney failure.

Renal Late Effects After the Treatment of Unilateral Nonsyndromic Wilms Tumor.

Wilms tumor is the most common renal malignancy of childhood. Because of the improvement in prognosis and the increase in survival rates, long-term consequences of the treatment for Wilms tumor are of greater concern. We investigated late renal effects of the treatment on 50 survivors of nonsyndromic unilateral Wilms tumor. After the second year since the cessation of treatment, the glomerular filtration rate (GFR), urinary protein excretion, urinary β2 microglobulin levels, and blood pressure as well as the general health status were assessed. Results were analyzed for correlation with clinical variables, chemotherapy, and radiotherapy as possible risk factors. At a median follow-up time of 8.8 years (mean=10.9; range, 2.3 to 35.4 y), none of the patients developed end-stage renal disease. Compensatory hypertrophy was observed in 68% of the cases. The median maximum bipolar length was significantly higher in patients diagnosed after the age of 36 months. Eleven (22%) and 2 (4%) of the 50 patients were hypertensive at the time of the diagnosis and the study, respectively. Similarly, median GFR values were significantly lower at the time of diagnosis, although at the time of the study, all patients had normal GFR values. With longer follow-up intervals, especially after 10 years, a significant decreasing trend in the GFR was observed (P=0.002).

Renal function in survivors of nonsyndromic Wilms tumor treated with unilateral radical nephrectomy.

Partial nephrectomy is considered by some for children with unilateral Wilms tumor (UWT) to avoid the theoretical complication of renal insufficiency. In the current study, the authors evaluated the prevalence of hypertension and impaired renal function in long-term survivors of nonsyndromic UWT who were treated without nephrotoxic chemotherapy or ionizing radiation. Eligibility included age ≤15 years at the time of diagnosis of nonsyndromic UWT, treatment receipt before 2002, and maintenance of disease remission after unilateral nephrectomy without receipt of abdominal irradiation or nephrotoxic chemotherapy. Renal function was assessed by urinalysis and estimated glomerular filtration rate (eGFR). Patients receiving antihypertensive medication or those with blood pressure readings of >140/90 mm Hg were considered to be hypertensive. A total of 75 patients with a median age at diagnosis of 3.2 years (range, 0.2-12.1 years) met eligibility criteria. The median length of follow-up was 19.6 years (range, 10.0-32.8 years). All but 1 patient had stage I/II disease. Sixty-eight patients (90.7%) patients had WT with favorable histology and 7 patients had anaplastic histology. Sixteen patients (21.3%) had an eGFR <90 mL/minute/1.73m(2), 2 of whom also had proteinuria (12.5%). No patient had an eGFR <60 mL/minute/1.73m(2). Five patients (6.7%) had hypertension, 3 of whom were receiving antihypertensive medications. At the time of last follow-up, no patient had developed end-stage renal disease. Patients with UWT who were treated with unilateral radical nephrectomy without nephrotoxic chemotherapy or ionizing radiation appear to be at low risk of developing significant long-term renal dysfunction. For this patient population, the routine use of partial nephrectomy does not appear justified. However, monitoring and counseling are important for identifying the rare patient who develops subtle renal insufficiency and therefore might be at an increased risk of adverse cardiovascular sequelae.

Nephron Sparing Surgery for Unilateral Non-Syndromic Wilms Tumor

The initial therapy for most children with Wilms tumor is radical nephrectomy. Several centers, have explored the role of Nephron-sparing procedures in children with unilateral non-syndromic Wilms tumors. The primary motivation for this approach is concern about late occurrence of renal dysfunction after unilateral nephrectomy. We report our experience with NSS for unilateral non-syndromic Wilms tumor. We reviewed the records of nine children who underwent nephron sparing surgery for unilateral, nonsyndromic Wilms tumors at our Hospital between Jan 2000 through Jan 2012. All patients received preoperative chemotherapy with two drugs (vincristine, and dactinomycin) following which patients underwent tumor resection. Subsequent renal function was assessed by estimating the glomerular filtration rate using creatinine clearance and other measures of long-term renal function assessment included blood pressure evaluation and the need for antihypertensive medications. During the study period nine children with a mean age 19.66 ± 14.37months at diagnosis and presenting with unilateral non-syndromic Wilms tumor underwent nephron sparing surgery. In all the nine children, the renal plane of resection showed a tumor-free margin. Post-operative serum creatinine repeated at the end of 3 months revealed maintenance of good renal function in all children. Nephron sparing surgery is a safe and effective option in the management of early stage unilateral non-syndromic Wilms tumor. It is oncologically safe and does not lead to decreased local tumor control. The function of the kidney remnant remains rather well.

Response Re: Evaluation of renal function after successful treatment for unilateral, non‐syndromic Wilms tumor

Pediatric Blood & CancerVolume 61, Issue 6 p. 1138-1138 Letter to the Editor Response Re: Evaluation of renal function after successful treatment for unilateral, non-syndromic Wilms tumor Daniel M. Green MD, Corresponding Author Daniel M. Green MD Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee Correspondence to: Daniel M. Green, Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 735, Memphis, TN 38105-2794. E-mail: [email protected]Search for more papers by this author Daniel M. Green MD, Corresponding Author Daniel M. Green MD Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee Correspondence to: Daniel M. Green, Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 735, Memphis, TN 38105-2794. E-mail: [email protected]Search for more papers by this author First published: 18 December 2013 https://doi.org/10.1002/pbc.24903Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume61, Issue6June 2014Pages 1138-1138 RelatedInformation

Evaluation of renal function after successful treatment for unilateral, non-syndromic wilms tumor

Impaired renal function may occur in experimental animals following surgical removal of most functioning renal tissue ("hyperfiltration injury"). Although end-stage renal disease is uncommon among long-term survivors of unilateral, non-syndromic Wilms tumor, concern has been expressed that there may be an increased risk of less serious, but progressive, renal function impairment among these individuals. The recent development of equations for estimating glomerular filtration rate (eGFR) has facilitated the study of renal function in Wilms tumor survivors. However, the estimating equations were developed to categorize individuals with chronic kidney disease and have significant limitations with regard to the accuracy of individual GFR estimates. These limitations must be considered when utilizing the estimating equations in cross-sectional or longitudinal evaluations of renal function in cohorts of patients who have been treated successfully for Wilms tumor or other childhood cancers.

Familial Occurrence of Nonsyndromic Wilms Tumor—A Report in Two Siblings

Nephroblastoma, (otherwise known as nephroblastoma) a second most common malignant neoplasm in childhood has been reported in twins, siblings & successive generations. We report two cases of Wilms tumor in female and male siblings first noticed in each at 14months of age. No congenital anomalies were observed in these patients. Both patients were treated with surgery & histopathology of both the specimens showed a well differentiated Wilms tumor with favourable histology. On follow up both the patients are alive and in complete remission, 4years after the diagnosis in female & 6months after the diagnosis in the male sibling.

Wilms tumor and constitutional epigenetic defects

Constitutional epigenetic defects affecting the 11p15.5 imprinted region cause a number of syndromic conditions involving birth defects. Now, an analysis of a large cohort of individuals with nonsyndromic Wilms tumor demonstrates the presence of known and newly identified constitutional IGF2-H19 imprinting defects, extending the phenotype associated with soma-wide 11p15.5 imprinting disorders.

Constitutional 11p15 abnormalities, including heritable imprinting center mutations, cause nonsyndromic Wilms tumor

Constitutional abnormalities at the imprinted 11p15 growth regulatory region cause syndromes characterized by disordered growth, some of which include a risk of Wilms tumor. We explored their possible contribution to nonsyndromic Wilms tumor and identified constitutional 11p15 abnormalities in genomic lymphocyte DNA from 13 of 437 individuals (3%) with sporadic Wilms tumor without features of growth disorders, including 12% of bilateral cases (P = 0.001) and in one familial Wilms tumor pedigree. No abnormality was detected in 220 controls (P = 0.006). Abnormalities identified included H19 DMR epimutations, uniparental disomy 11p15 and H19 DMR imprinting center mutations (one microinsertion and one microdeletion), thus identifying microinsertion as a new class of imprinting center mutation. Our data identify constitutional 11p15 defects as one of the most common known causes of Wilms tumor, provide mechanistic insights into imprinting disruption and reveal clinically important epigenotype-phenotype associations. The impact on clinical management dictates that constitutional 11p15 analysis should be considered in all individuals with Wilms tumor.

Renal cell carcinoma as a second malignant neoplasm in a patient with non-syndromic hemihypertrophy and previous Wilms tumor

Survivors of childhood Wilms tumors are at an increased risk of second malignant neoplasms. Recently, it has been postulated that renal cell carcinoma is among the malignancies for which this population is at risk. We present the unique case of an adult Wilms tumor survivor with non-syndromic hemihypertrophy (NSHH) who developed renal cell carcinoma. This case highlights the need for close follow-up in two populations: adults who have survived Wilms tumor and those with NSHH.

Frequency and heritability of WT1 mutations in nonsyndromic Wilms' tumor patients: a UK Children's Cancer Study Group Study.

Constitutional WT1 mutations in patients with Wilms' tumor (WT) have specifically been associated with genitourinary abnormalities, such as cryptorchidism and hypospadias. We sought to ascertain the frequency and heritability of constitutional WT1 mutations in nonsyndromic WT patients. Constitutional DNA from 282 patients treated at seven United Kingdom Children's Cancer Study Group centers was screened for WT1 mutations using heteroduplex analysis. Bidirectional sequencing was used to confirm the mutation and to analyze the corresponding parental DNA samples. Five different constitutional WT1 mutations were identified in six children. Mutations in four patients were confirmed to be de novo, and all five mutations are predicted to produce truncated protein. The WT1 mutation group had a young median age at diagnosis of 13.8 months, compared with 34.9 months in the group in whom no WT1 mutations were found; four were female and two were male; and all tumors were of favorable histology. The three tumors with known histologic subtype were stromal-predominant. Contrary to expectation, four of six mutations occurred in children with unilateral tumors without any associated genitourinary abnormality. Constitutional WT1 mutations occur with a low frequency (2.1%; 95% CI, 0.8% to 4.6%) in nonsyndromic WT patients. Most mutations occurred in children with unilateral WT without associated genitourinary abnormalities, creating difficulties in identifying individuals with germline mutations on phenotype alone. Two factors that may indicate that an individual is carrying a germline WT1 mutation are an early age of onset and stromal-predominant histology of the WT.