Clinical aspects of the rhabdoid tumor of the kidney: A report of the national wilms' tumor study group

Rhabdoid tumor of the kidney (RTK), originally described as a monophasic sarcomatous variant of Wilms' tumor, is now recognized as a highly malignant, non-Wilms' tumor possibly of neuroectodermal origin. Twenty-one National Wilms' Tumor Study patients with this tumor were treated in the years 1969 through 1978. Mean patient age was 18 months with 16 of the 21 younger than 2 years at diagnosis. Two patients were Stage I, 10 Stage II, 5 Stage III, and 4 Stage IV. One patient only is continuously disease free and another is surviving disease free following excision of bilateral pulmonary metastases. One patient died of sepsis early during therapy. Thus 18 of the 19 patients who relapsed died, 15 within 1 year of diagnosis, all with progressive tumor growth. The rapid appearance of metastases (mean 4 months), often to multiple sites, and short subsequent survival signal a very malignant tumor resistant to current treatment stratagems.     

Wilms' Tumor with Intracardlac Extension: Chemotherapy Before Surgery

The article describes two Chinese boys ages 2 and 3 years with unilateral Wilms' tumors complicated by intracaval and intracardiac extension. In contrast to the previously recommended treatment with surgery followed by chemotherapy and radiation therapy, the children were managed primarily with combination chemotherapy before definitive operation. Reduction of tumor sire on serial imaging was documented, and no viable tumor cells were found when the involved kidney and right atrium were explored. Both patients remained alive without evidence of disease more than 5 years after initial diagnosis. A literature search revealed case reports and retrospective analyses of 70 patients with Wilms's tumors and intracardiac involvement, and a tendency toward preoperative chemotherapy with or without the addition of radiation therapj was obsemed. The overall outcome of this group of patients parallels the outcome of those without intracardiac extension ty hology and stage. Wilms's tumor presenting with extension into the inferior vem cava and right atrium is thus rare and renders the affected child with additional cardiovascular complications and operative risks. As a result of the uncommon occurrence, a consensus on managemnt based on prospective study would be dfficult. The present report and the literature are supportive of the use of preoperative chemotherapy in the initial management of advanced Wilms's tumor extending into the right atrium.     

Der(16)t(1;16)(q21;q13) in Wilms' tumor: Friend or foe

The der(16)t(1;16)(q21;q13) chromosomal abnormality has been reported rarely in Wilms' tumor. This abnormality has also been found in several other pediatric and adult neoplasms, and may imply a poor prognosis in at least some of these solid tumors. To investigate its clinical significance in Wilms' tumor, we examined the records of 65 consecutive children with Wilms' tumor whose tumor cells were successfully karyotyped. The t(1;16) was present in seven patients (10%) whose ages ranged from 2.5 to 4.7 years (median 3.5 years) at diagnosis. Six of the seven patients were female. All four stages of Wilms' tumor were represented (two patients had stage IV disease). No patient had bilateral disease. All tumors were of “favorable histology.” All seven patients are alive and off therapy with a median follow-up of 3.2 years (range, 2 to 8.5 years). One patient with this abnormality developed brain metastases within 4 months of completion of therapy. Comparison of these patients with the remaining 58 Wilms' tumor patients revealed no significant differences with regard to disease stage, histology, survival, or relapse-free survival. Cytogenetic evidence of der(16)t(1;16)(q21;q13) in Wilms' tumor does not appear to portend an adverse clinical outcome, although only a larger study that includes molecular detection methods can provide more conclusive evidence. © 1996 Wiley-Liss, Inc.     

Phase II study of carboplatin as a single drug for relapsed Wilms' tumor: Experience of the Brazilian Wilms' tumor study group

A total of 15 patients with relapsed Wilms' tumor were treated with carboplatin as a single agent. There were six females and nine males, aged between 2 and 9 years (me-dian:5). The treatment consisted of carboplatin given I.V. as a single agent at a dose of 550 mg/m² over 1 hour every 3 weeks. There were four (26%) complete responses, four (26%) partial responses, one stable disease, and six with progressive disease. In all patients a total of 56 courses were given and the toxicities found were leukopenia and thrombocytopenia. The overall response rate was encouraging and the toxicity was acceptable and reversible. © 1994 Wiley-Liss, Inc.     

Wilms' tumor involving the inferior vena cava: Preoperative evaluation and management

Neoplastic invasion of the inferior vena cava due to renal tumors (especially Wilms' tumor) is uncommon in children. The tumor thrombus, according to the aggressiveness of the original neoplasm, can extend in diverse ways, obliterate the vascular lumen completely, and even reach the right atrium. The luminal thrombus might be accompanied by the involvement of the caval wall, which requires wide vascular resection. The purpose of this paper is to present our experience with 7 children, aged 18 months and 6 years, affected by caval invasion due to Wilms' tumor. Furthermore, the diagnostic techniques and the surgical treatment in simple caval thrombosis and in associated invasion of the caval wall are described.     

Histological analysis of aggressiveness and responsiveness in Wilms' tumor

The clinical behavior and outcome for any neoplasm are determined originally by its aggressiveness. As adjuvant therapy becomes increasingly effective for that neoplasm, responsiveness to therapy assumes a larger role in determining outcome. Wilms' tumor (WT) provides instructive examples of the dissociation of aggressiveness from responsiveness. The presence of gigantic nuclei with multipolar mitotic figures (anaplasia) appears to be a marker of resistance to therapy, but not of increased aggressiveness. For this reason, anaplasia in a stage I WT and anaplasia confined to discrete foci within the primary tumor have no adverse prognostic significance following surgical resection. The prognostic significance of anaplasia is apparently limited to those patients in whom anaplastic cells remain following attempted surgical resection. WT with predominantly epithelial differentiation usually have a low degree of aggressiveness. In this study, 81.3% of WT with this pattern were stage I. This feature accounts for the high cure rate associated with this pattern prior to the advent of effective adjuvant therapy. However, epithelial predominant WT that present with advanced stage disease may be quite resistant to therapy, with relapse and death rates higher than for more aggressive WT patterns. In contrast, the diffuse blastemal pattern is associated with marked aggressiveness, but with high survival rates suggesting it is usually responsive to current therapy. These features illustrate the independence of aggressiveness and responsiveness in determining outcome for some patients with cancer. Grading systems must be reevaluated with each significant change in therapy. In order to formulate rational therapy, it is important to determine whether prognostic markers are associated with aggressiveness or responsiveness. © 1996 Wiley-Liss, Inc.     

Hemihypertrophy,bilateral Wilms' tumor,and clear-cell adenocarcinoma of the uterine cervix in a young girl

We report the case of a young girl who had hemihypertrophy and developed Wilms' tumor in both kidneys and clear-cell adenocarcinoma of the uterine cervix with no maternal history of stilbestrol ingestion during pregnancy. Karyotype on the second Wilms' tumor showed monosomy 22. The link between hemihypertrophy and Wilms' tumor is well known, but their association with clear-cell carcinoma of the cervix has not been previously described. © 1993 Wiley-Liss, Inc.     

Epidural metastasis in Wilms' tumor: A case report and review of the literature

Spinal canal involvement is not a common pattern of metastasis in Wilms' tumor. Although early detection and treatment can achieve improvement of neurological deficit, mortality remains high. We present a 5-year-old girl who had an epidural metastasis while she was receiving chemotherapy for stage IV Wilms' tumor. Within 2 months following laminectomy, total removal of tumor, radiotherapy, and adjuvant chemotherapy some of the neurological signs improved. © 1994 Wiley-Liss, Inc.     

Establishment of a patient-derived Wilms' tumor xenograft model: A promising tool for individualized cancer therapy

ObjectiveLack of appropriate approaches that reliably predict response of Wilms' tumor (WT) to anticancer agents remains a major deficiency in clinical practice of individualized cancer therapy. The aim of this study was to establish a patient-derived tumor tissue (PDTT) xenograft model of WT for individualized chemotherapeutic regimen selection in accordance with the patient's tumor nature.Material and methodsTumor specimens of a primary WT were orthotopically implanted into three nude mice, and after 4 weeks xenografts were harvested for serial heterotopic transplantation in 20 nude mice that were divided into three experimental groups and one control group. In vitro and in vivo chemosensitivity to doxorubicin, actinomycin-D, and vincristine were evaluated. Hematoxylin and eosin (H&E) staining and immunohistochemical examination with desmin, vimentin, myogenin, and neuron-specific enolase (NSE) were also applied to determine histological stability of the xenograft during serial transplantation compared with the original tumor tissue.ResultsThe xenograft model was successfully established. Histopathologic characteristics of the xenograft tumors were similar to the patient's tumor. Early passage of the PDTT showed a similar chemosensitivity pattern to the original tumor tissue.ConclusionsPDTT xenograft of WT provides an appropriate model for individualized cancer therapeutic regimen selection by means of its biological stability compared with original patient's tumor.     

Screening for Wilms' tumor in children with high-risk congenital syndromes: Considerations for an intervention trial

Screening for cancer in children is uncommon. However, in children with congenital syndromes associated with Wilms' tumor, conditions exist that potentially make screening effective. This select population of children 1) are relatively easily identified; 2) have a high incidence of Wilms' tumor; 3) if identified before development of Wilms' tumor, may have a decrement in morbidity/mortality; and 4) are amenable to a simple and acceptable screening technology, renal sonography exams. Many clinicians have recommended screening for cancer in children with congenital syndromes associated with Wilms' tumor. However, neither costs nor effectiveness of such recommendations have been evaluated systematically. The strongest evidence for or against Wilms' tumor screening in this select population would be provided by a randomized screening trial. Prior to undertaking such a trial, the key parameters that dominate the cost and effectiveness of screening should be identified. Simulation models, such as cost-effectiveness analysis, offer a starting point for deciding whether cancer screening is appropriate, and if so, under what set of conditions. We review basic conditions required for a successful screening trial in children with syndromes that are at increased risk of Wilms' tumor. We also discuss the use of cost-effectiveness analysis as a preliminary step in determining the feasibility of an intervention trial. © 1996 Wiley-Liss, Inc.     

Inflammatory pseudotumor of the liver masquerading as a metastasis in a child treated for nephroblastoma

A 31/2-year-old boy presented with a palpable hepatic tumor thought on clinical and radiological grounds to be a metastasis but which was found to be an inflammatory pseudotumor on histological examination. Eighteen months previously he had received chemotherapy and radiotherapy for a stage IV Wilms' tumor, which had been surgically excised 4 months after commencing treatment. This case illustrates the importance of obtaining a histological diagnosis in the management of patients with malignant tumors.     

Renal failure in Wilms' tumor patients: A report from the National Wilms' Tumor Study Group

This report defines the incidence and determines the etiology of renal failure (RF) in patients undergoing treatment for Wilms' tumor (WT). The database of the National Wilms' Tumor Study (NWTS) was searched to identify all children reported to have developed chronic renal failure. There were 55 patients found to have RF. Of these, 39 patients had bilateral tumors, 15 with unilateral disease and one with a WT in a solitary kidney. The median interval from diagnosis to the onset of renal failure was 21 months. The incidence of RF in bilateral WT was 16.4% for NWTS-1 & -2, 9.9% for NWTS-3, and 3.8% for NWTS-4. The incidence of RF in unilateral WT remained stable. The most common etiologies of RF were: bilateral nephrectomy for persistent or recurrent tumor (24 pts), Drash syndrome (12 pts), progressive tumor in the remaining kidney (5 pts), radiation nephritis (6 pts), and other causes (5 pts). The etiology of renal failure was not reported in three children. Children with unilateral WT and a normal contralateral kidney have a very low incidence of RF, and this review does not support a recommendation for parenchymal sparing procedures in these patients. Children with bilateral WT are at risk for the development of RF, and parenchymal sparing procedures are warranted. © 1996 Wiley-Liss, Inc.     

Radiotherapy in the SIOP (international society of pediatric oncology) nephroblastoma studies: A review

For decades radiation has generally been accepted as a valuable supplement to surgery in the treatment of Wilms' tumor; unfortunately, it may produce undesirable late effects. It turned out, however, that when treatment is adjusted to known variables, the risk for late sequelae can be diminished in some groups of children. SIOP clinical trials have been based on children with unilateral tumors of standard histology and free of metastasis at diagnosis. The first two clinical trials, SIOP-1 (started in 1971) and SIOP-2 (started in 1974), established the beneficial effect (such as less ruptures, lower stage) of preoperative radiation and actinomycin D (AMD) in SIOP-2, with all children having radiation therapy either pre-operatively, postoperatively, or both. In the SIOP-5 trial (started in 1977), preoperative radiation therapy and AMD were compared with preoperative chemotherapy resulting in only 50% of children having radiation. The result permitted disuse of preoperative radiation in the SIOP-6 trial (started in 1980), where only one-third of the patients received postoperative radiation therapy. At present, in the SIOP-9 trial (started in 1987), fewer than 20% of children are having radiotherapy. The survival rates meanwhile have been increasing steadily from 64% in SIOP-1 to 84% in SIOP-6 for stages I, II, and III combined. © 1994 Wiley-Liss, Inc.     

Wilms' tumor: A rational use of preoperative imaging

Objective—To determine whether a preoperative imaging protocol relying predominantly on a chest X-ray film (CXR) and ultrasound in patients with Wilms' tumor is adequate for patient management and to determine the frequency more sophisticated imaging, in particular, computed tomography (CT), is required. Design and setting—Historical cohort study at a tertiary pediatric hospital. Subjects—60 consecutive patients with Wilms' tumor treated at our institution between 1980 and 1990. Main outcome measure—The preoperative imaging was recorded and 2- and 4-year survival were compared with the National Wilms' Tumor Study. Results—100% of patients had a preoperative CXR, 95% abdominal ultrasound, 5% abdominal CT, 13% chest CT, 47% abdominal X-ray, 2% aortography, 5% cavography, and 35% intravenous urography. The overall 2- and 4-year survivals of 92% and 90%, respectively, did not statistically differ from the National Wilms' Tumor Study 2- and 4-year survivals of 94% and 91%. Conclusions—A preoperative imaging protocol relying predominantly on a CXR and abdominal ultrasound does not reduce survival. Other more sophisticated imaging, in particular, CT, is not required in the majority of cases and is warranted only when a CXR or ultrasound is unable to resolve relevant management problems. © 1995 Wiley-Liss, Inc.     

Toxocariasis simulating hepatic recurrence in a patient with Wilms' tumor

We report the case of a 3-year-old girl with stage I Wilms' tumor of favorable histology. During the course of chemotherapy 5 months post-diagnosis, an abdominal ultra-sonogram revealed hypoechoic areas consistent with hepatic tumor recurrence. A liver biopsy performed to rule out recurrence of the malignancy was suggestive of toxocariasis and the diagnosis was confirmed by serologic testing. Although the patient had few classic signs of visceral larva migrans, her eosinophilia and family social history should have suggested this possibility. This case demonstrates that hepatic toxocariasis should be considered in evaluating hepatic hypoechoic lesions in a child, even when features typical of the disease are absent. © 1994 Wiley-Liss, Inc.