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Background: Between 2005 and 2014, Ghana's Wilms tumor (WT) 2-year disease-free survival of 44% trailed behind that of high-income countries. This study aimed to uncover social determinants of health leading to preventable WT death in Ghana., Methods: WT patient records (2014-2022) at Korle-Bu Teaching Hospital (KBTH; Ghana) were reviewed retrospectively. Demographics, clinical course, tumor characteristics, and survival were evaluated using t-tests, Pearson Chi-square, and multivariate Cox logistic regression., Results: Of 127 patients identified, 65 were female. Median age was 44 months [IQR 25-66]. Forty-eight patients (38%) presented with distant metastasis (75% lung, 25% liver), which associated with hypoalbuminemia (p = 0.009), caregiver informal employment (p = 0.04), and larger tumors (p = 0.002). Despite neoadjuvant chemotherapy shrinking 84% of tumors, larger initial size associated with incomplete resection (p = 0.046). Of 110 nephrectomies, 31 patients had residual disease, negatively impacting survival (p = 2.7 × 10 -5 ). Twenty-two patients (17%) abandoned treatment (45% before nephrectomy; 55% after nephrectomy), with seven patients ultimately lost to follow-up (LTFU). Decedents represented 43% of stage IV patients compared to 28% in other stages. Event-free survival (EFS) was 60% at 4 years with overall survival (OS) at 67%., Conclusions: Although Ghana's WT survival has improved, informal employment and distance from KBTH predisposed patients to delayed referral, greater tumor burden, hypoalbuminemia, and lower survival., Type of Study: Prognosis Study., Level of Evidence: II., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Wilms tumor (WT), or nephroblastoma, is the most common primary malignant renal tumor of childhood. It is an embryonal tumor that develops from remnants of immature kidney. There are approximately 500 new WT cases diagnosed in the United States every year. Advances in multimodal therapy including surgery, chemotherapy, and radiation therapy given according to risk stratification have allowed most patients to achieve survival rates in excess of 90%., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Bilateral Wilms tumor (BWT) is a rare entity. The goal of this study is to report outcomes (overall and event-free survival, OS/EFS) of BWT in a large cohort representative of the Canadian population since 2000. We focused on the occurrence of late events (relapse or death beyond 18 months), as well as outcomes of patients treated following the only protocol specifically designed for BWT to date, AREN0534, compared to patients treated following other therapeutic schemes., Methods: Data was obtained for patients diagnosed with BWT between 2001 and 2018 from the Cancer in Young People in Canada (CYP-C) database. Demographics, treatment protocols, and dates for events were collected. Specifically, we examined outcomes of patients treated according to the Children's Oncology Group (COG) protocol AREN0534 since 2009. Survival analysis was performed., Results: 57/816 (7%) of patients with Wilms tumor had BWT during the study period. Median age at diagnosis was 2.74 years (IQR 1.37-4.48) and 35 (64%) were female; 8/57 (15%) had metastatic disease. After a median follow-up of 4.8 years (IQR 2.8-5.7 years, range 0.2-18 years), OS and EFS were 86% (CI 73-93%) and 80% (CI 66-89%), respectively. Less than 5 events were recorded after 18 months from diagnosis. Since 2009, patients treated according to the AREN0534 protocol had a statistically significant higher OS compared to patients treated with other protocols., Conclusions: In this large Canadian cohort of patients with BWT, OS and EFS compared favorably to the published literature. Late events were rare. Patients treated according to a disease-specific protocol (AREN0534) had improved overall survival., Type of Study: Original article., Level of Evidence: Level IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This article reviews of the current evidence-based treatment standards for children with Wilms tumor. In this article, a summary of recently completed clinical trials by the Children's Oncology Group is provided, the current diagnostic evaluation and surgical standards are discussed, and the surgical impact on current risk stratification for patients with Wilms tumor is highlighted. LEVEL OF EVIDENCE: This is a review article of previously published and referenced LEVEL 1 studies, but also includes expert opinion LEVEL V, represented by the American Pediatric Surgical Association Cancer Committee., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Wilms' tumor(WT) is the most common malignant renal tumor of childhood. Despite the good prognosis of WT, bilateral Wilms' tumor (BWT) still has a poor outcome. We systematically reviewed the literature on BWT, aiming to define its clinical features, treatment, and outcomes., Methods: PubMed, OVID EMbase, Web of Science, and Cochrane Library were systematically searched for studies published from 1980 to 2017. Case series and comparative studies reported clinical data of BWT patients were included., Results: A total of 32 studies comprising 1457 patients were retained for primary outcome. Hemihypertrophy, cryptorchidism, and Beckwith-Wiedemann syndrome(BWS) are the most common congenital anomalies and syndrome. 86% of patients had favorable histology (FH). Patients with local stage I or II accounted for 64%, and 12.6% had metastasis at diagnosis. Bilateral nephron-sparing surgery (NSS) was achieved in 33.8%. Recurrence and renal failure occurred in 20% and 8%. The overall survival (OS) was 73%. In comparative studies, OS of patients undergoing bilateral NSS was similar to that of other operation types., Conclusion: Prognosis of BWT has been improved but is significantly poorer than WT. Bilateral NSS was recommended by most centers to preserve more renal volume. However, finding a balance between retaining renal function and avoiding recurrence remains a question., Type of Study: Systematic review., Level of Evidence: Level IV., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Though the volume-outcome relationship has been well-established in adults, low mortality rates and small sample sizes have precluded definitive demonstration in children. This study compares treatment-specific factors for children with nephroblastoma at high (HVC) versus low volume centers (LVC)., Methods: We performed a retrospective cohort study comparing patients ≤18years with unilateral nephroblastoma treated at HVCs and LVCs using the National Cancer Data Base (1998-2012). Definitions of HVCs included performing above the median, the upper two quartiles, and the highest decile of nephroblastoma resections. Outcomes included nodal sampling, margin status, time to chemotherapy and radiation, and survival. Statistical analyses included χ 2 , t-tests, generalized linear, and Cox regression models (p<0.05)., Results: Of 2911 patients from 210 centers, 1443 (49.6%) were treated at HVCs. There was no difference in frequency of preoperative biopsy or days to radiation (p>0.05). High volume centers were more likely to perform nodal sampling (RR 1.04, 95%CI 1.01-1.08) and had fewer days to chemotherapy (RR 0.80, 95%CI 0.69-0.93). Five-year survival was similar (HVC: 0.93, 95%CI 0.92-0.94; LVC: 0.93, 95%CI 0.91-0.94)., Conclusions: HVCs were more likely to perform nodal sampling and had fewer days to chemotherapy. There was no difference in days to radiation or survival between centers., Level of Evidence: Level II (retrospective prognosis study)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The 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)., Methods: Surgical 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 99m Tc-DTPA scanning. Urine studies, including microalbumin, β-microglobulin, and FE Na were also reviewed., Results: Forty-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/1.73m 2 , while the median eGFR Schwartz and eGFR CKiD were 103.3mL/min/1.73m 2 and 79.7mL/min/1.73m 2 , 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; FE Na >1%, n=4)., Conclusions: In 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 Evidence: Level IV - retrospective case series with no comparison group., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The Children's Oncology Group (COG) renal tumor study (AREN03B2) requires real-time central review of radiology, pathology, and the surgical procedure to determine appropriate risk-based therapy. The purpose of this study was to determine the inter-rater reliability of the surgical reviews., Methods: Of the first 3200 enrolled AREN03B2 patients, a sample of 100 enriched for blood vessel involvement, spill, rupture, and lymph node involvement was selected for analysis. The surgical assessment was then performed independently by two blinded surgical reviewers and compared to the original assessment, which had been completed by another of the committee surgeons. Variables assessed included surgeon-determined local tumor stage, overall disease stage, type of renal procedure performed, presence of tumor rupture, occurrence of intraoperative tumor spill, blood vessel involvement, presence of peritoneal implants, and interpretation of residual disease. Inter-rater reliability was measured using the Fleiss' Kappa statistic two-sided hypothesis tests (Kappa, p-value)., Results: Local tumor stage correlated in all 3 reviews except in one case (Kappa=0.9775, p<0.001). Similarly, overall disease stage had excellent correlation (0.9422, p<0.001). There was strong correlation for type of renal procedure (0.8357, p<0.001), presence of tumor rupture (0.6858, p<0.001), intraoperative tumor spill (0.6493, p<0.001), and blood vessel involvement (0.6470, p<0.001). Variables that had lower correlation were determination of the presence of peritoneal implants (0.2753, p<0.001) and interpretation of residual disease status (0.5310, p<0.001)., Conclusion: The inter-rater reliability of the surgical review is high based on the great consistency in the 3 independent review results. This analysis provides validation and establishes precedent for real-time central surgical review to determine treatment assignment in a risk-based stratagem for multimodal cancer therapy., (© 2014.)

Purpose: Survival from Wilms Tumor (WT) exceeds 90% at 5 years in developed nations, whereas at last report, 2-year event-free survival (EFS) in Kenya reached only 35%. To clarify factors linked to these poor outcomes in Kenya, we established a comprehensive web-based WT registry, comprised of patients from the four primary hospitals treating childhood cancers., Materials and Methods: WT patients diagnosed between January 2008 and January 2012 were identified. Files were abstracted for demographic characteristics, treatment regimens, and enrollment in the Kenyan National Hospital Insurance Fund (NHIF). Children under 15 years of age having both a primary kidney tumor on imaging and concordant histology consistent with WT were included., Results: Two-year event-free survival (EFS) was 52.7% for all patients (n=133), although loss to follow up (LTFU) was 50%. For the 33 patients who completed all scheduled standard therapy, 2-year EFS was 94%. Patients enrolled in NHIF tended to complete more standard therapy and had a lower hazard of death (Cox 0.192, p < 0.001)., Conclusion: Survival of Kenyan WT patients has increased slightly since last report. Notably, WT patients completing all phases of standard therapy experienced 2-year survival approaching the benchmarks of developed nations. Efforts in Kenya should be made to enhance compliance with WT treatment through NHIF enrollment., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to review the management of children with Wilms' tumour who have intracardiac extension., Patients and Methods: Data were collected from patient notes regarding presentation, operative details, and outcome., Results: From 1984 through 2011, 264 children with Wilms' tumour were treated at our hospital. Nine (3.4%) had cavo-atrial extension of the tumour thrombus. The thrombus extended into the right ventricle in two children and involved the hepatic veins in both, and also two others. Pre-operative chemotherapy was administered in eight children with complete regression of the intra-cardiac tumour thrombus in two cases. One child died preoperatively of septicaemia and respiratory failure after two doses of chemotherapy. Six children with intra-cardiac tumour were operated on under cardiopulmonary bypass (CPB) with deep hypothermia and circulatory arrest (DHCA). The mean ischemic time was 30 min. There was one peri-operative death in a child with hepatic vein involvement and Budd-Chiari syndrome. All others made a good postoperative recovery. All tumours were favourable histology. To date four children are still alive and disease free. Three children have died as a result of pulmonary metastases., Conclusion: Intracardiac extension of Wilms' tumour is rare, and the management is technically challenging. Pre-operative chemotherapy is effective. CPB and DHCA for excision of the cavo-atrial tumour thrombus may be necessary. Distant metastatic disease is common and determines long term prognosis. Hepatic vein extension complicates surgery and remains challenging., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the clinicopathological features that indicate relapse and suggest a new risk based therapeutic strategy for unilateral Favorable Histology Wilms Tumor (FH-WT)., Materials & Methods: Thirty-three patients with unilateral WT were treated in two institutions between 1986 and 2010. Twenty-eight patients with FH-WT received primary nephrectomy according to the National Wilms' Tumor Study (NWTS) or the Japanese Wilms' Tumor Study (JWiTS) protocol. Retrospective analyses of the non-relapsed group (n=23) and the relapsed group (n=5) compared age, gender, tumor laterality, tumor weight, initial tumor stage, known histological subtype, chemotherapy (2 or 3 drugs), and any irradiation delivered. Stages and histological subtypes of the tumors were re-evaluated according to the Japanese staging system., Results: Five of the twenty-eight tumors relapsed, and one patient died. The initial staging (P=0.029) and the histological subtype (P=0.003) were the only factors indicating relapse. Nine of the twenty-three tumors were histologically classified as blastemal predominant subtype (BPT-WT). Five relapsed., Conclusion: According to the basic Japanese therapeutic strategy, all patients underwent a primary nephrectomy before chemotherapy. This study suggests that the histological subtype pre-treatment "BPT-WT" should be included as a strong indicator of poor prognosis. Such patients should be treated as a high-risk group., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background and Purpose: The strategy used to treat pediatric renal tumors in Japan is based on the Japanese Wilms' Tumor Study (JWiTS) protocol, which was based on the National Wilms' Tumor Study (NWTS)-5 regimen. The regimen is characterized by an initial radical operation, followed by adjuvant chemotherapy and radiotherapy. Concerning the histological classification, a new classification based on the International Society of Pediatric Oncology (SIOP) classification was used beginning in 2008. The main points of revision are that the "blastemal predominant type" was classified as an independent category in the Wilms' tumor subtypes. The purpose of this study was to analyze the biological characteristics from the standpoint of the newly established histological classification., Materials and Methods: From 1971 to 2005, 174 cases of Wilms' tumors treated with an initial operation followed by adjuvant therapy were re-evaluated by the new histological classification. Histologically, all these materials showed no secondary changes associated with adjuvant therapy., Results: According to the new classification, Wilms' tumors were classified into four subtypes, including the mixed type (n=112), epithelial type (n=17), mesenchymal type (n=15), and blastemal predominant type (n=26). The 5 year overall survival rates were as follows; mixed type (90.1%), epithelial type (100%), mesenchymal type (93.3%), and blastemal predominant type (65.4%)., Conclusion: The patients with blastemal predominant tumors demonstrated a significantly worse prognosis compared with those of other subtypes. The treatment strategy of blastemal predominant category should be distinguished from the other favorable subtypes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Extrarenal Wilms tumor is extremely rare, and only 25 cases in children have been reported to date in Japan. A 2-year-old girl presented with a large left lower quadrant abdominal mass. Abdominal computed tomography revealed a retroperitoneal tumor located below the left kidney. At laparotomy, the tumor was encapsulated without evidence of metastasis to other abdominal organs. Pathologic diagnosis of the tumor was extrarenal Wilms tumor with diffuse anaplasia. After complete tumor resection, chemotherapy was administered according to the treatment protocol (Regimen I) of the Japan Wilms Tumor Study Group. Cyclophosphamide and etoposide were administered in combination with vincristine and doxorubicin. Two years after treatment, the patient has had no evidence of recurrence., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This case report documents the eighth reported case of renal cell carcinoma (RCC) occurring after treatment of Wilms tumor. Although secondary malignancies after treatment of Wilms tumors are not infrequent, RCC as the second malignancy is rare. We discuss a 17-year-old girl whose RCC was diagnosed 12.5 years after diagnosis of a Wilms tumor. In addition, we review the literature on the subject. Renal cell carcinoma has been proposed as a consequent of chemoradiation; however, a genetic susceptibility must be considered. Because it is routine to assess the functional status of the remaining solitary kidney by annual ultrasonography, we recommend assessing for the presence of secondary renal malignancies and perhaps continuing routine ultrasounds long-term., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: Although occasionally difficult, distinguishing abdominal neuroblastoma (NBL) from Wilms tumor (WT) at presentation is important, as surgical management differs significantly. We reviewed our 20-year experience (1987-2006) treating patients with NBL, focusing on those with an initial diagnosis of WT, to determine presenting features that would have suggested the correct preoperative diagnosis., Methods: Retrospective case cohort study reviewing charts and imaging of patients with NBL initially diagnosed clinically with WT. Preoperative symptoms, laboratory studies, and imaging were evaluated. Similar variables were assessed in the 20 patients with WT most recently treated at our institution., Results: Nine patients with NBL were identified as those who had an exploratory laparotomy with a preoperative diagnosis of WT; 8 underwent nephrectomy at exploration. Children with NBL had symptoms such as fever and weight loss at presentation (67%) more often than patients with WT (20%). Preoperative computed tomography demonstrated intratumoral calcifications, vascular encasement, or both in 78% of patients with NBL but were never seen in WT patients. Of interest, preoperative urinary catecholamines were elevated in 5 patients ultimately diagnosed with NBL., Conclusion: Although NBL can be mistaken for WT at presentation, the presence of constitutional symptoms, or intratumoral calcification or vascular encasement on preoperative imaging should heighten suspicion for NBL. In addition, laboratory evaluation, including urinary catecholamines, should be completed before surgery when the etiology of an abdominal tumor is uncertain.

Background/purpose: This study aimed to illustrate the first report of extrarenal Wilms tumor occurring in a family., Materials and Methods: Retrospective case note review of 3 siblings, 2 of which presented with extrarenal Wilms tumor. Immunohistochemical analysis for WT1 gene product was performed together with molecular genetic linkage studies., Results: A 3-year-old boy had excision of a right-sided extrarenal retroperitoneal Wilms tumor and nephrectomy followed by chemotherapy. At follow-up of 4 years, the boy was well and thriving. Aged 2 years, his sister developed a left-sided retroperitoneal extrarenal Wilms tumor. She had a tumor excision and nephrectomy followed by chemotherapy. She was well on follow-up more than a year after completion of treatment. Immunohistochemical analysis identified WT1 gene product within the tumor for both cases. Molecular genetic linkage studies showed no linkage between the index cases at FWT1 locus. Although possible linkage was demonstrated at WT1 locus, no mutation was found in the coding sequence and intron/exon boundaries of WT1 gene in index patient 1. A possible linkage between the index cases was also found at FWT2 locus. This could be a chance event because of the close relationship of the 2 patients., Conclusions: We could identify extrarenal Wilms tumor in a family for the first time. Immunohistochemical analysis showed WT1 gene products in both cases. Linkage studies for Wilms tumor genes within the family were inconclusive. The possible linkage between the 2 index cases may be a chance event.

This article provides a summary of renal cancers that can affect adolescent patients. It encompasses both isolated and syndrome-associated cancers and the various renal complications associated with cancer therapy. Prompt recognition and appropriate referral and management, along with periodic long-term follow-up, will enhance both the survival and quality of life of young people afflicted with these serious diseases.

Over the past 3 decades, enormous advances have been made in the creation of a standardized treatment protocol for Wilms' tumor. Less morbid regimens for low-risk patients and more efficacious aggressive treatment protocols for high-risk patients have been developed, and continue to be improved with newer studies, such as the NWTS-V. An area that has posed a more challenging aspect of the disease is its relapse. Although a standard follow-up protocol has been produced by in-depth evaluation of previous works, there has been a great deal of difficulty demonstrating improved relapse-free and overall survival rates in re-treatment of children suffering from recurrent Wilms' tumor. Several factors are involved in the success of treatment of relapse, some of which include prerelapse treatment of initial disease and stage, site, and timing of recurrence. New agents and their combination with chemotherapeutics that already have established efficacy are being used for treatment of Wilms' tumor relapse, with varying success. These studies should lead the way for newer investigations in the future. Patients with anaplastic disease, rhabdoid tumors, and clear cell sarcoma are especially in need of these future investigations. Perhaps the true final frontier is establishing the likelihood of patients suffering a relapse. This topic currently is being studied in the fields of biologic markers and gene expression. This knowledge will hopefully, in turn, tailor initial treatment in a more specific manner.

Background: The human epidermal growth factor family (HER) members play a significant role in the mesenchymal-to-epithelial transition during renal tubulogenesis. HER misexpression has been linked also to loss of growth control, invasiveness, and promotion of angiogenesis in breast cancers and other human malignant tumors, Methods: The authors screened Wilms' tumor samples and derived cell lines for expression of her2/neu, which was detected in both unfavorable and favorable histology tissues. Xenografts were implanted in mice using her2/neu(+) and her2/neu(-) cell lines and the effect of specific blockade tested using monoclonal anti-her2/neu antibody., Results: Blocking antibody suppressed tumor growth in her2/neu(+) but not her2/neu(-) experimental Wilms' tumor. In addition, antibody exposure resulted in suppression of tumor angiogenesis but no decrease in tumor cell proliferation in her2/neu(+) xenografts., Conclusions: Her2/neu contributes to the growth of some Wilms' tumors, and an important mechanism of its action is promotion of angiogenesis.

The authors report an unusual case of Wilms' tumor. The tumor grew transureterally into the urinary bladder, became dislodged, and presented as recurrent urinary infection with retention of urine after the child underwent nephroureterectomy. Such a presentation has not been reported earlier.

Background/purpose: An increased incidence of Wilms tumor has been noted in patients with a horseshoe kidney. These represent a difficult diagnostic and therapeutic challenge. The charts of all National Wilms Tumor Study Group (NWTSG) patients with Wilms tumor occurring in a horseshoe kidney were reviewed., Methods: From 1969 to 1998, 8,617 patients were enrolled in the NWTSG. Forty-one patients were found to have a Wilms tumor arising in a horseshoe kidney for an incidence of 0.48%. Their records were reviewed retrospectively., Results: Horseshoe kidney was not recognized preoperatively in 13 patients, 10 of whom were evaluated with computed tomography (CT). Four of the 10 also had renal ultrasonography and one an intravenous pyelogram (IVP). Two of the 13 were evaluated with an IVP only, and the last had no preoperative imaging studies performed. Stage at presentation was stage I, 10 pts; stage II, 10; stage III, 12; stage IV, 6; stage V, 3. Primary surgical resection was performed in 26 patients, including 23 nephrectomies and 3 partial nephrectomies. Fifteen children were treated with preoperative chemotherapy after initial biopsy of the tumor. The mean total remaining renal parenchyma after all operations (excluding treatment of relapses) was approximately 75%. Surgical complications occurred in 14.6% of patients, including 2 urine leaks, 2 ureteral obstructions, and 1 ureteral injury. Two patients had transient renal failure., Conclusions: The diagnosis of horseshoe kidney often was missed on preoperative imaging. Accurate preoperative diagnosis is important in planning the operative approach and may help to decrease complications related to transection of the urinary collecting system. Although 37% of patients with Wilms tumor arising in a horseshoe kidney were judged inoperable at initial exploration, all were amenable to resection after chemotherapy., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Background/purpose: Suicide gene therapy based on the delivery of the herpes simplex virus thymidine kinase gene combined with ganciclovir (HSV-tk/GCV) is a promising approach for cancer treatment. Adenoviral (Ad) vectors are useful gene delivery vehicles for this approach; however, because these agents possess a high natural tropism for the liver, systems must be designed to avoid potential hepatotoxicity induced by expression of the therapeutic gene in this organ. It has been reported that Wilms' tumors or neuroblastomas express a high level of midkine (MK), a heparin-binding growth factor. In addition, no MK expression is observed in mouse or human liver. The authors investigated the application of MK promoter-based adenoviral gene therapy for MK-positive tumors, especially Wilms' tumors or neuroblastomas, and have shown that the MK promoter retains its fidelity in the adenoviral context, having low activity in liver and high activity in MK-positive tumor cells. We present herein the efficacy of in vivo tumor regression as well as prevention of lethal hepatic toxicity by using the MK promoter in an Ad vector-based HSV-tk/GCV treatment approach., Methods: Ad vectors, AdMKTK or AdCMVTK, encoding HSV-tk under the control of the MK or cytomegalovirus promoters, respectively, were injected systemically into mice, then hepatotoxicity and survival was monitored after GCV administration. In concurrent studies, the therapeutic impact of AdMKTK/GCV versus AdCMVTK/GCV on subcutaneous G-401 Wilms' tumors in nude mice was assessed., Results: By day 8 of systemic viral treatment, 4 of 5 mice treated with AdCMVTK/GCV had died, whereas all mice treated with AdMKTK/GCV survived at least 10 days. In the subcutaneous tumor study, equivalent regression of tumor was seen in the group that received AdMKTK as the group that received AdCMVTK intratumoral injection., Conclusion: These data indicate that the MK promoter-based adenoviral suicide gene therapy is a unique therapeutic candidate for MK-positive tumors, Wilms' tumors, or neuroblastomas, by virtue of its mild hepatotoxicity and high efficacy against MK-positive tumors., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Wilms' tumor with tumor extension into the vena cava is a not uncommon variant of tumor presentation. Typically, this extension is nonadherent to the endothelium and readily lends itself to removal either before or after chemotherapy. This case illustrates an unusual variant in which the tumor within the cava was tightly adherent to the venous wall and required the complete excision of the vena cava, left renal vein, and a portion of the iliac system.

Background/purpose: Pathologic angiogenesis in tumors is a potential target for novel therapies. Vascular endothelial growth factor (VEGF) is an angiogenic promoter present in a wide variety of human tumors. VEGF is expressed as 4 isoforms; one of these, VEGF165, predominates in human tumors. The authors hypothesized that antagonism of VEGF165 by a specific aptamer would block tumor growth in an experimental model of Wilms tumor., Methods: VEGF isoform expression in clinical (n = 2) and experimental tumors were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Tumors were induced in NCR nude mice (n = 32) by intrarenal injection of 10(6) cultured Wilms tumor cells. At 1 week, aptamer (n = 16) or vehicle (n = 16) treatment was started and continued daily for 5 weeks., Results: At 6 weeks tumors weighed 84% less in treated versus control animals (0.69 v 4.41 g; P <.028), without observed adverse effects and similar to suppression previously reported using nonisoform-specific anti-VEGF antibody (94% to 96%)., Conclusions: Anti-VEGF165 aptamer effectively suppressed primary tumor growth in experimental animals with no observed adverse effects. Development of highly specific antiangiogenic therapies may be of particular benefit to pediatric patients.

Background/purpose: Neuroblastoma and Wilms tumor exhibit different patterns of metastasis, invasion, and therapeutic response. Vascular endothelial growth factor (VEGF) is an angiogenic factor expressed in both tumors. The authors hypothesized that because the clinical behavior of these tumors differs, the response to anti-VEGF therapy would be distinct, and tumor vascular architectures would reflect this distinction., Methods: Xenografts were induced by intrarenal injection of cultured cells in athymic mice. After 1 week, anti-VEGF antibody or vehicle were administered for 5 weeks before sacrifice. Additional animals were maintained for 3 weeks after termination of antibody injections to assess rebound growth of tumors. Fluorescein angiography was performed in selected animals., Results: Neuroblastoma control and treated tumor weights were not significantly different (1.48 g v 0.77 g, P =.34). By comparison, as previously reported, antibody-treated Wilms tumors were growth inhibited. Angiograms of treated (but not control) neuroblastomas displayed novel rounded structures at vessel branches, which the authors term terminal vascular bodies (TVBs). Wilms tumor vessels displayed no such alteration., Conclusions: Neuroblastoma xenografts are less effectively suppressed by anti-VEGF antibody than Wilms tumors. Neuroblastoma vascular architecture displays a novel alteration during antibody administration, which attenuates when antibody is withdrawn. These studies suggest that angiogenesis is differently regulated in experimental neuroblastoma and Wilms tumor.

Background/purpose: Recent studies have reported a high incidence of p53 mutations in anaplastic Wilms' tumors (WT). Restoration of the normal p53 state by current gene therapy techniques is thus an attractive potential mode of therapy for this tumor, which is poorly responsive to standard therapy. The purpose of this study is to determine whether gene delivery of normal p53 is possible and to characterize the subsequent effect of restoring the wild-type p53 state., Methods: Anaplastic WT RM1 cells (mutant p53) were transduced with replication-deficient adenoviral vectors containing either the wild-type p53 gene (rAd-p53) or the gene encoding a green fluorescent protein (rAd-GFP). The transduction efficiency of adenovirus for RM1 cells was determined by flow cytometric analysis of rAd-GFP-transduced cells. The effect of p53 transduction on cell viability was evaluated using a colorimetric proliferation assay. Apoptosis was evaluated by labeling DNA breaks using a TUNEL assay (Apo-Direct kit)., Results: Cells treated with increasing concentrations of viral particles relative to tumor cells (multiplicity of infection-MOI) showed a dose-dependent increase in the number of cells transduced. Twenty-four hours after viral treatment, the percentage of cells transduced for MOIs of 10, 50, 100, and 500 was 29.5, 60.9, 74.6, and 92.4, respectively; at 48 hours the percentage of cells transduced increased to 70.8, 90.7, 93. 7, and 96.3, respectively. Viral treatment at an MOI of 50 reduced cell proliferation by 10% at 17 hours and 97% at 5 days; at an MOI of 100, the relative reduction in proliferation was 15% and 99.8%, respectively. When assayed, 30% of cells became apoptotic at an MOI of 50, and 48% at an MOI of 100., Conclusions: Highly efficient delivery of the p53 tumor suppressor gene by adenoviral vector to anaplastic WT is possible. Subsequent restoration of the normal p53 state results in reduced viability and increased apoptosis. Gene replacement of p53 may represent a novel therapeutic agent for anaplastic Wilms' tumors.

Since its inception in 1969, the NWTSG has performed successful studies that are now the model for the management of pediatric malignancies. Future studies may use genetic markers to stratify high-risk patients beyond the traditional staging system. Therapy will continue to be evaluated to determine the minimal therapy necessary to achieve the best outcome for children with Wilms' tumor.

Purpose: The aim of this study was to assess the accuracy of computed tomography (CT) in the local staging of Wilms' tumor., Methods: Twenty-six patients with unilateral, nonmetastatic Wilms' tumors were accrued over the period of 1990 through 1997. Preoperative CT staging was performed before surgical biopsy or excision. The abdominal CT images were reviewed and staged for local disease according to National Wilms' Tumour Study (NWTS) Group Staging V as either intrarenal disease (Stage I), local extrarenal extension amenable to complete local excision (Stage II), or advanced local disease (Stage III). Patients with metastatic (Stage IV) and bilateral disease (Stage V) were excluded from our study. Results were compared to histological findings., Results: CT scan correctly staged 10 of 26 cases (38%) of Wilms' tumor. CT scan overstaged 12 of 16 (75%) localized renal disease (Stage I) and local extension (Stage II) tumors, and understaged 4 of 10 (40%) localized spread (Stage III) tumors., Conclusions: CT scan appears to have poor correlation to histological staging. Therefore, basing therapy solely on radiological imaging may lead to some patients receiving more intense therapy than necessary, whereas others do not receive sufficient therapeutic regimens. Histological assessment of the excised mass should remain the standard for staging Wilms' tumors.

Background/purpose: Vascular endothelial growth factor (VEGF) has been shown previously to correlate with tumor growth and metastasis in an experimental model of anaplastic Wilms' tumor. The authors hypothesized that treatment with anti-VEGF antibodies would suppress both primary tumor growth and metastasis in this model., Methods: Tumors were induced in the right kidneys of nude mice by the injection of cultured Wilms' tumor cells. After 1 week, anti-VEGF treatment was begun with injection of either vehicle or an anti-VEGF antibody intraperitoneally. Mice were killed after 4.5 weeks of treatment and tumor weights and the incidence of metastases evaluated., Results: Anti-VEGF treatment resulted in a greater than 95% reduction in tumor weight (P < .0001). Anti-VEGF treatment also abolished the establishment of lung metastases (40% in control animals, P < .003). Cessation of treatment resulted in rebound tumor growth., Conclusion: Anti-VEGF therapy can suppress both primary tumor growth and the establishment of metastases in experimental anaplastic Wilms' tumor.

Inguinal and scrotal Wilms' tumors are extremely rare; only 15 cases have been reported to date. The authors report a case of inguinal Wilms' tumor (stage III), which occurred in a previously healthy 3 1/2-year-old boy who was staged and treated according to currently accepted National Wilms' Tumor Study III criteria. The exact embryological origin of this tumor has not been determined. However, there is evidence that the origin is more primitive than that of intrarenal Wilms' tumor.

Children with Beckwith-Wiedemann syndrome (BWS) have an increased risk of developing Wilms' tumors, hepatoblastomas, and adrenal tumors. This study evaluates disease-free survival in children with BWS and intraabdominal tumors. Sixteen tumors occurred in 13 children with BWS (8 boys, 5 girls). Diagnoses included Wilms' tumor (10) (2 bilateral, 20%), hepatoblastoma (2), bladder rhabdomyosarcoma (1), and adrenal cortical tumor (1). In the 10 children with Wilms' tumor, the average age at diagnosis was 3.5 years (range, 7 months to 5 years). Nine of 10 had initial tumor resection, chemotherapy, and radiation therapy (when indicated). One child with bilateral disease had tumor biopsy, chemotherapy, and partial nephrectomy. Tumors were classified as stage I (5), stage II (2), stage IV (1) and stage V (2), all with favorable histology. Disease-free survival rate was 100% with median follow-up of 9 years (range, 4 to 22 years). One patient had a left adrenal tumor detected during screening sonography 11 years after Wilms' tumor resection. Two infants with advanced-stage hepatoblastoma responded to chemotherapy, allowing subsequent complete hepatic resection. Both tumors had unfavorable histology. Both completed postoperative chemotherapy and have no evidence of disease (NED) with normal alpha-fetoprotein levels at 21 and 12 months, respectively, after tumor detection. One patient with stage III (group 3) bladder rhabdomyosarcoma underwent partial cystectomy following chemoradiation and is alive (NED) after 20 months. Children with BWS should be screened at regular intervals (every 3 to 6 months) for renal, adrenal, and hepatic tumors. The exact duration of screening is not yet determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal renal tumors are very rare. We have identified 15 cases of Wilm's tumors diagnosed in the first 30 days of life. The most common presentation was an abdominal mass on routine newborn examination, and three tumors were noted on an antenatal ultrasound. All of the infants underwent primary excision of the tumor. Five infants were not given postoperative chemotherapy after surgical excision. One of these children had a relapse and later died of progressive disease. The remaining children are alive at a median follow-up of 31 months. Eight of the tumors had evidence of nephrogenic rests. More frequent follow-up physical and imaging examinations are indicated in children not given adjuvant chemotherapy or whose tumors show nephrogenic rests.

Childhood cancer is the leading cause of death from disease in children between 1 and 15 years of age. Since the introduction of modern multimodality therapy, the prognosis for solid tumors has improved dramatically, with 50% to 60% cure rates. Advances in cytogenetic and molecular genetic techniques are now being used for risk-based treatment in various tumors, including neuroblastoma and rhabdomyosarcoma. Further use of these research tools may lead to a better understanding of oncogenic molecular events, permitting treatment targeted to specific genetic lesions. This article focuses on the clinical features, treatment, and potential future research directions for this diverse group of diseases.

Wilms' tumor is the most common malignant tumor of the kidney in children. Although only 500 cases per year are diagnosed in the US, the tumor has been studied extensively in the National Wilms' Tumor Committee Cooperative Studies. These prospective studies have led to improved survival and at the same time reduced treatment and complications in the more favorable cases. Similar results have been shown by the European cooperative study group SIOP using different treatment protocols. These studies have identified a group of tumors with unfavorable histology that are more resistant to treatment and will require more intensive protocols. Diagnosis of Wilms' tumor by the finding of a large flank mass in an otherwise healthy-appearing child is usually easy. Imaging techniques of CT or IVU will give accurate confirmation of Wilms' tumor in 95% of children. Modern treatment in the US by radical nephrectomy followed by chemotherapy with or without radiotherapy depends on tumor stage and histology. Early-stage tumors with favorable histology can be controlled by shorter courses of two-drug treatment (dactinomycin and vincristine) without radiation. Advanced tumors respond to treatment but require more intensive chemotherapy combined with radiation. The final challenge is the child with a tumor of unfavorable histology, particularly if there is advanced-stage disease. Whereas Wilms' tumor showing favorable histology now has a survival rate exceeding 90%, survival of those with tumors of unfavorable histology remains poor. The European (SIOP) studies have shown similar survival figures using preoperative chemotherapy. This technique produces shrinkage of tumors, making them less hemorrhagic and producing a lower incidence of rupture at subsequent surgery. Preoperative chemotherapy does not change the histologic diagnosis of Wilms' tumor and is a useful alternative approach for the large hemorrhagic or infiltrating tumors.

A retrospective review of the treatment of Wilms' tumor from 1967 to 1977 at the Royal Children's Hospital, Melbourne, was undertaken, allowing a minimum 2-yr followup. Fifty-four (77%) of the 70 patients in the study are alive, with 23/25 (92%) in Stage I, 12/16 (75%) in Stage II, 12/19 (63%) in Stage III, and 7/9 (78%) in Stage IV. Survival was significantly better in Stage I disease, and those patients less than 5-yr-old at presentation. Recurrence of disease was significantly lower after the introduction of multiple courses of chemotherapy in 1971. Sixteen deaths occurred during the period: three infants from drug toxicity, four patients with "unfavorable" sarcomatous histology, and four patients with recurrent local disease, where irradiation had been confined to the tumor bed after tumor spill with recurrence beyond the irradiated field.

Review of cases and of published reports of patients with bilateral Wilms' tumor revealed a significantly higher mortality rate in those who had received a renal transplant than in those who had not. The increased mortality is attributed to overwhelming sepsis resulting from chemotherapy, radiotherapy and immunosuppression. Growth of the tumor did not appear to be accelerated by immunosuppression and transplantation.

Bilaterality is uncommon in Wilms' tumor, being present in 4% to 8% of the cases. We report the combined experience of two children's hospitals in one city over a 20-year period. We encountered nine cases of synchronous bilateral nephroblastoma (National Wilms' Tumor Study 3, stage V). Age at diagnosis ranged from 9 to 41 months (mean 23 months). There were five girls and four boys. Associated findings include nephroblastomatosis in three cases (33%), one of which also had a familial history; undescended testis in two cases; and minor anomalies in two other cases. Surgical treatment consisted of unilateral nephrectomy with contralateral partial nephrectomy or tumorectomy in six cases, nephrectomy with contralateral biopsy only in two cases, and the other patient had bilateral biopsies initially, followed at a later date by partial nephrectomy on one side. All patients received chemotherapy; actinomycin D (AMD) only was used in the oldest case, vincristine and AMD in five cases, to which was added cyclophosphamide in one case and adriamycin in two. Seven patients received radiation therapy. Seven out of the nine patients survived more than 2 years (77%); five are well, off chemotherapy, with no evidence of disease from 4 to 11 years after diagnosis. Two patients suffered from chronic renal failure and one died from complications after renal transplantation more than 19 years after diagnosis. The two patients who died from their disease presented with more advanced tumor. Therefore, the agressiveness of multimodal therapy can be tailored according to stage and histology, and effective chemotherapy allows maximal preservation of renal parenchyma in patients with stage I and II tumors.

Recent improvements in the treatment of children with nephroblastoma have led to an increase in the disease-free survival rate. The late effect of treatment on long-term survivors requires assessment to determine whether avoidable iatrogenic disorders are appearing. The onset of puberty is one measurement of physical development and has been used in the study to assess the progress of 16 children over the age of 12 yr who were treated for nephroblastoma. The method consisted of the measuring body height, weight and testicular size, estimating serum levels of luteinizing hormone, follicular stimulating hormone and testosterone, recording the age at menarche, and staging of pubic hair and breast development. There was evidence of complete ovarian suppression in 3 out of 10 girls and of delayed and testicular function in 1 out of 6 boys. Analysis of the treatment received by the children implicated radiotherapy as the responsible factor causing gonadal suppression.

The extrarenal location of Wilms' tumor is extremely rare. These tumors can arise from other neoplasms, generally teratomas, or they can present without any associated teratomatous elements. We encountered only 19 well-documented cases of isolated extrarenal nephroblastoma, and we describe three previously unreported patients with this disease. Two of the three children presented also with horseshoe kidneys, an association that may have clinical and embryologic significance. The presence of tumor cephalad to a horseshoe kidney is easier to explain when we consider that they originate from primitive mesodermal tissue, probably mesonephric rests, and not from metanephric remnants. Also, this association should alert physicians to the possible diagnosis of extrarenal nephroblastoma in patients with a retroperitoneal mass and horseshoe kidneys. These patients should be treated according to the same protocols as those for patients with intrarenal Wilms' tumor.

Between 1973 and 1983, eight children who had undergone successful multimodal management of malignant tumors developed secondary thyroid neoplasms. The primary tumors were acute lymphocytic leukemia in three, Wilms' tumor in two, and Hodgkin's disease, rhabdomyosarcoma, and ganglioneuroblastoma in one each. During this period, 174 long-term survivors with these five diagnoses were enrolled in our tumor registry, yielding a 4.6% incidence of secondary thyroid neoplasms. All eight patients received both radiation and chemotherapy. The mean radiation dose was 2,700 r with a calculated thyroid dose of 2,140 r (range, 5 to 4,200 r). Age of diagnosis of the primary tumors ranged from 1 to 8 2/12 years (mean, 5 years), and the latent period between treatment and development of the thyroid lesions averaged 6 1/2 years. Thyroid neoplasms presented at an average age of 11 4/12 years. Five patients developed solitary adenomas, one presented with multiple adenomas, and two had follicular carcinoma with regional lymph node metastases. Although thyroid neoplasms are rare in childhood, clinically apparent thyroid tumors have been observed in up to 2.5% of children following radiation exposure (mean follow-up, 24 years). The reported latent period before the development of thyroid neoplasms in irradiated patients is at least 10 years, with the peak incidence occurring 20 to 25 years after exposure. This study documents a 4.6% incidence of subsequent thyroid neoplasms in pediatric cancer patients within a relatively short follow-up period (mean, 11 years). These thyroid tumors occurred at an earlier age (mean, 11.5 years) and with a shorter latent period (mean, 6.5 years) than would be predicted from previous studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent studies indicate a favorable outcome with bilateral Wilms' tumor. From 1971 to 1985, ten children between the ages of 6 months and 5 years were treated for this disease. During the early part of the series, five patients had nephrectomy on one side and partial nephrectomy on the other side, and one patient had bilateral partial nephrectomies at the same operation. More recently four patients initially had a biopsy of both tumors and lymph node sampling followed by chemotherapy. At the second-look procedure two patients had multiple biopsies because there was no obvious tumor. Histologically there was no tumor on the third-look procedure in these two patients. Nine patients had a favorable histology of the Wilms' tumor. One patient had a favorable histology on one side and an unfavorable type of histology on the other side. Eight patients are surviving between 6 months and 13 years. Two died of extensive disease within 16 months of diagnosis. One patient had an unfavorable histology. The good results following partial nephrectomies have led us to attempt to conserve additional tissue, as has been done in the last four patients. Our early results suggest biopsy of the tumor followed by chemotherapy, then a second look, and if necessary, third-look procedures may result in preservation of functioning renal tissue.

This is a brief report of a patient with Wiedemann-Beckwith syndrome and nephroblastoma with metastases, apparently cured by surgery, chemotherapy, and radiation.

Nodular renal blastema and nephroblastomatosis were present in 8 of 118 patients (6.8%) with Wilms' tumor. Five of these 8 patients (63%) had bilateral Wilms' tumors. Two had hemihypertrophy. Preoperative renal angiograms were accurate in detecting these metanephric anomalies. The surgical approach consisted of removal of the most diseased kidney and biopsy for diffuse tumors and wedge resections for localized tumors for the remaining kidney. Postoperatively, radiation was administered when tumor extended outside the kidney. Chemotherapy consisted of vincristine and dactinomycin for 18 mo and adriamycin for 6 mo. This method of management resulted in tumor-free survival of these 8 patients for 1--44 mo (median 24 mo). Nodular renal blastema and nephroblastomatosis may possibly develop into Wilms' tumor. All of these three conditions respond to surgery, chemotherapy, and radiation. When a Wilms' tumor is encountered, it is better to explore and possibly biopsy the opposite kidney. There is a place for second-look laparotomy in this spectrum of congenital anomalies.

Mesoblastic nephroma is a distinctive pathologic renal tumor with unique clinical, therapeutic, and prognostic patterns. This report reviews 51 patients (2.8% of 1905 patients submitted to NWTS with renal tumors) with this diagnosis from the NWTS contrasting this disease entity with Wilms' tumor. There were 33 males and 18 females, predominantly term babies born after uncomplicated pregnancies. The mean age at tumor excision was 3.44 +/- 0.6 mo (one child 9 yr). A palpable mass was the predominant presentation in 48 patients and in addition hematuria (9), hypertension (2), vomiting (3), and jaundice (1) were noteworthy. Diagnostic studies included IVP (49 positive, 2 negative) and ultrasound (15 positive, 1 negative). Adequate operative excision was achieved in 43 of 51 patients while 8 children had local extension and 10 had tumor spillage. Operation alone (23), predominantly since 1978, surgery plus chemotherapy (24), prior to 1978, and surgery, chemotherapy, and radiation therapy (4), prior to 1976, were the modes of therapy. The follow-up ranges from 4 mo to 11.5 yr. Survival was excellent; 50 patients survive (98%), only 1 dying of sepsis. These data suggest that mesoblastic nephroma contrasts with Wilms' tumor in that it occurs in a younger age group, has a benign biologic behavior, and a more favorable outcome. Aggressive multimodal treatment though utilized in the early years of the study is not essential to achieve this outcome.

Twenty two children with advanced retroperitoneal neuroblastoma and one child with advanced posterior mediastinal neuroblastoma admitted to our clinic were treated as follows. Seven patients (group A) underwent primary resection of tumor immediately after diagnosis. In two patients of this group, the levels of VMA and HVA in urine after surgery decreased to nearly normal (group A-I), while they did not change appreciably in the other 5 patients (group A-II). Seven patients (group B) underwent resection of tumor following complete or partial response to preoperative chemotherapy. Nine patients (group C) did not undergo resection of the tumor except for exploratory laparotomy. Two group A-I patients have survived, free of disease, for 6 months and 12 months after diagnosis. All patients of group A-II died within a year. Residual tumors of 4 patients of this group began to grow explosively just after surgery, although they received persistent postoperative chemotherapy. Four patients of group B survived for more than two years and the two patients of this group who received continuous intra-arterial PGE1 therapy had no postoperative explosive growth of residual tumors. Two patients in group C survived for 20 months and the others died within a year. Primary tumors and metastatic foci responded well to therapy as compared with group A-II, which suggests that presence of primary tumors may inhibit rapid growth of metastatic foci. Resection of primary tumors, therefore, was not always conducive to survival unless residual tumor responded to postoperative chemotherapy.

The influence of capsular and vascular invasion on prognosis was determined retrospectively in 52 children with Wilms' tumor. Local recurrence was more prevalent (0.26) in patients with rupture or capsular invasion than in any other group. Inadequate postnephrectomy irradiation or infiltration of the liver by nephroblastoma cells appeared to be predisposing factors in the development of these reccurrences. Of the 26 patients with gross or microscopic vascular invasion, 13 developed metastasis. This proportion was significantly higher than in patients without vascular involvement (p less than 0.05). These observations emphasize the importance of microscopic detection of capsular and vascular invasion in staging of Wilm's tumor.