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The survival of childhood Wilms tumor is currently around 90%, with many survivors reaching reproductive age. Chemotherapy and radiotherapy are established risk factors for gonadal damage and are used in both COG and SIOP Wilms tumor treatment protocols. The risk of infertility in Wilms tumor patients is low but increases with intensification of treatment including the use of alkylating agents, whole abdominal radiation or radiotherapy to the pelvis. Both COG and SIOP protocols aim to limit the use of gonadotoxic treatment, but unfortunately this cannot be avoided in all patients. Infertility is considered one of the most important late effects of childhood cancer treatment by patients and their families. Thus, timely discussion of gonadal damage risk and fertility preservation options is important. Additionally, irrespective of the choice for preservation, consultation with a fertility preservation (FP) team is associated with decreased patient and family regret and better quality of life. Current guidelines recommend early discussion of the impact of therapy on potential fertility. Since most patients with Wilms tumors are prepubertal, potential FP methods for this group are still considered experimental. There are no proven methods for FP for prepubertal males (testicular biopsy for cryopreservation is experimental), and there is just a single option for prepubertal females (ovarian tissue cryopreservation), posing both technical and ethical challenges. Identification of genetic markers of susceptibility to gonadotoxic therapy may help to stratify patient risk of gonadal damage and identify patients most likely to benefit from FP methods., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify the driving factors that are distinctive for this aggressive subtype. In our study, we compared gene expression profiles of 33 tumor biopsies (17 blastemal and 16 other tumors) after neoadjuvant chemotherapy. The analysis of this dataset using the Regulator Gene Association Enrichment algorithm successfully identified several biomarkers and associated molecular mechanisms that distinguish between blastemal and nonblastemal Wilms tumors. Specifically, regulators involved in embryonic development and epigenetic processes like chromatin remodeling and histone modification play an essential role in blastemal tumors. In this context, we especially identified TCF3 as the central regulatory element. Furthermore, the comparison of ChIP-Seq data of Wilms tumor cell cultures from a blastemal mouse xenograft and a stromal tumor provided further evidence that the chromatin states of blastemal cells share characteristics with embryonic stem cells that are not present in the stromal tumor cell line. These stem-cell like characteristics could potentially add to the increased malignancy and chemoresistance of the blastemal subtype. Along with TCF3, we detected several additional biomarkers that are distinctive for blastemal Wilms tumors after neoadjuvant chemotherapy and that may provide leads for new therapeutic regimens., (© 2018 UICC.)

Circulating tumor DNA (ctDNA) is a powerful tool for the molecular characterization of cancer. The most frequent pediatric kidney tumors (KT) are Wilms' tumors (WT), but other diagnoses may occur. According to the SIOP strategy, in most countries pediatric KT have a presumptive diagnosis of WT if they are clinically and radiologically compatible. The histologic confirmation is established after post-chemotherapy nephrectomy. Thus, there is a risk for a small fraction of patients to receive neoadjuvant chemotherapy that is not adapted to the disease. The aim of this work is to perform molecular diagnosis of pediatric KT by tumor genetic characterization based on the analysis of ctDNA. We analyzed ctDNA extracted from plasma samples of 18 pediatric patients with KT by whole-exome sequencing and compared the results to their matched tumor and germline DNA. Copy number alterations (CNAs) and single nucleotide variations (SNVs) were analyzed. We were able to detect tumor cell specific genetic alterations-CNAs, SNVs or both-in ctDNA in all patients except in one (for whom the plasma sample was obtained long after nephrectomy). These results open the door to new applications for the study of ctDNA with regards to the molecular diagnosis of KT, with a possibility of its usefulness for adapting the treatment early after diagnosis, but also for disease monitoring and follow up., (© 2018 UICC.)

Certain magnetic fields (MF) have potential therapeutic antitumor effect whereas the underlying mechanism remains undefined. In this study, a well-characterized MF was applied to two common childhood malignancies, nephroblastoma and neuroblastoma. This MF has a time-averaged total intensity of 5.1 militesla (mT), and was generated as a superimposition of a static and an extremely low frequency (ELF) MF in 50 Hertz (Hz). In nephroblastoma and neuroblastoma cell lines including G401, CHLA255, and N2a, after MF exposure of 2 h per day, the cell viability decreased significantly after 2 days. After 3 days, inhibition rates of 17-22% were achieved in these cell lines. Furthermore, the inhibition rate was positively associated with exposure time. On the other hand, when using static MF only while maintaining the same time-averaged intensity of 5.1 mT, the inhibition rate was decreased. Thus, both time and combination of ELF field were positively associated with the inhibitory effect of this MF. Exposure to the field decreased cell proliferation and induced apoptosis. Combinational use of MF together with chemotherapeutics cisplatin (DDP) was performed in both in vitro and in vivo experiments. In cell lines, combinational treatment further increased the inhibition rate compared with single use of either DDP or MF. In G401 nephroblastoma tumor model in nude mice, combination of MF and DDP resulted in significant decrease of tumor mass, and the side effect was limited in mild liver injury. MF exposure by itself did not hamper liver or kidney functions. In summary, the antitumor effect of an established MF against neuroblastoma and nephroblastoma is reported, and this field has the potential to be used in combination with DDP to achieve increased efficacy and reduce side effects in these two childhood malignancies. Bioelectromagnetics. 39:375-385, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Nephroblastoma is a success of paediatric oncologic therapy, yet, there are still some cases where favourable response to preoperative chemotherapy is not achieved. Fine needle biopsy has the role of diagnostic confirmation and, idyllically of predicting a response to preoperative chemotherapy. To advance in this aim, we retrieved a total of 14 nephroblastomas, (seven male patients and seven female with a mean age of 44.4 months), diagnosed in our department by fine needle biopsy and submitted afterward to chemotherapy and nephrectomy, in the last 10 years. Correlation between cytologic features, (morphology, cell death, and proliferation (Ki-67 labelling index), and post chemotherapy tumour evaluation was done. Cytologic pattern per se was not predictive of histologic tumour classification (P = 0.6061). We did not find any correlation between the percentage of necrosis and apoptosis (P = 0.682) in cytologic smears and histologic regressive changes but when both these two criteria coexisted in cytologic blastemal component of nephroblastomas, this fact seemed to lead to a favourable response of the tumour to chemotherapy. When evaluation of Ki-67 labelling index was done in the blastematous component present in the smears, divergent results were obtained. The small number of cases prevented any firm conclusions. By summing up, our results support the idea that there are probably two types of blastema in nephroblastoma with different "suicide" potential and chemotherapeutic response. Further studies should be performed to stratify the influence of necrosis, apoptosis, and proliferation in chemosensivity of nephroblastomas., ((c) 2009 Wiley-Liss, Inc.)

Cancer treatment may affect school performance. School report grades after childhood lymphomas and Wilms tumor have not been previously reported. All Finnish patients with Wilms tumor (N = 74), Hodgkin lymphoma (HL) (N = 99) and non-Hodgkin lymphoma (NHL) (N = 94) who were born in 1974-1986 and had achieved the age of 16 years were identified from the Finnish cancer registry. Population controls (N = 1329) were matched for age, gender and residence. Their 9th grade school reports were obtained from Statistics Finland. The overall average and grades for mother tongue, first foreign language, mathematics and physical education were compared between the patients and their controls. Almost all the patients (>98%) had finished their comprehensive school. NHL patients had lower overall averages than their controls (difference -0.27 grade units; 95% CI -0.39, -0.15). Irradiation or age at diagnosis did not explain this difference in NHL patients. The grades of NHL patients were significantly lower than those of their controls in each academic school subject, especially in mathematics (-0.45; 95% CI -0.63, -0.27). In mother tongue, girls with irradiation had greatest difference (-0.66, 95% CI -0.99, -0.34) to their controls. Patients with HL and Wilms tumor performed similarly or even better than their controls in all academic subjects. Grades for physical education were impaired in Wilms tumor patients (-0.20; 95% CI -0.33, -0.06). Impairment of school report grades was observed in patients with NHL. The difference to controls was greatest in mathematics. The patients with HL and Wilms tumor, who had not received any central nervous system directed therapy, achieved equally good grades as their controls in all the academic subjects., ((c) 2008 Wiley-Liss, Inc.)

A British population-based cohort study was carried out to determine the risk of second primary neoplasms in survivors of Wilms' tumour. The cohort was obtained from the British Childhood Cancer Survivor Study, a population-based cohort study of treatment toxicities in 18,044 individuals diagnosed with childhood cancer, at an age of less than 15 years, between 1940 and 1991 in Britain. There were 1,441 Wilms' tumour survivors in the cohort: 732 males (50.8%) and 709 females (49.2%). Total follow-up from 5-year survival was 27,841 person years, mean follow-up of 19.3 years per survivor. There were 81 second primary neoplasms, including 52 solid neoplasms, 3 acute myeloid leukaemias and 26 basal cell carcinomas. Thirty-five of the 39 solid neoplasms that developed in the thoracic, abdominal or pelvic region occurred within irradiated tissue. The standardised incidence ratio for all solid second primary neoplasms was 6.7 (95% CI: 5.0-8.8). Cumulative incidence for all solid second primary neoplasms by ages 30, 40 and 50 years was 2.3% (1.4-3.5%), 6.8% (4.6-9.5%) and 12.2% (7.3-18.4%). The overall risk of second primary neoplasms in survivors of Wilms' tumour treated between 1940 and 1991 was substantial, and solid second tumours tended to develop in the irradiated tissue. Continued follow-up of these survivors is important to monitor such late effects of treatment. It is also important to evaluate the risk of second primary neoplasms following more recent lower radiation dose treatment practices., ((c) 2008 Wiley-Liss, Inc.)

The fine-needle aspiration cytologic findings of Wilms' tumor occurring in a 20-yr-old female patient and a 35-yr-old male patient showing blastemal, spindled sarcomatous and rare epithelial components are reported. The male patient had the typical presentation of renal mass with metastasis to lung and pleura, whereas the female patient had an unusual presentation with the tumor originated from the subcapsular nephrogenic zone of the kidney, extending into the liver without invasion into the renal cortex. Cytogenetic analysis of this case identified: 90, XXXX, +2x3-4, -5, -15, -16, -17, -17, i (17)(q10) x2. This finding may represent a genetic change associated with Wilms' tumor of older pediatric and young adult patients. To the best of our knowledge, this case is the sixth case with cytogenetic study and the first case revealing isochromosome 17q of an adult Wilms' tumor.

A broad spectrum of renal tumors occurs in infants and children ranging from the benign cystic nephroma to the extremely aggressive malignant rhabdoid tumor of the kidney. A thorough understanding of these tumors is crucial to the optimal diagnosis and management of children with renal masses. The common renal tumors in infants and children are discussed and an orderly method for their evaluation is presented. Recent developments in the molecular biology of Wilms' tumor are outlined to provide insight into the origin of this tumor.

Background: Fetal rhabdomyomatous nephroblastoma (FRN) is a rare variant of Wilms tumor., Materials and Results: One hundred and thirty two children with kidney tumors were seen at our hospital from 1985 to 1993. Among them were 6 (4.5%) who had FRNs. Five were boys aged 8 months to 3 years; the girl was 17 months old. Three of the four with unilateral disease had tumors so large that they were considered unresectable at diagnosis. Five received pre-operative chemotherapy and three also received pre-operative radiation therapy. None of the tumors responded. Both patients with bilateral tumors died of progressive disease. Three of the four patients with unilateral disease followed for at least one year are alive for 1 to 10 years after diagnosis., Conclusions: FRN should be in the differential diagnosis of huge kidney tumors in children, and preoperative therapies escalated with caution since FRN is not responsive to treatment used for classic Wilms tumor.

Introduction: Hepatotoxicity consistent with the clinical diagnosis of veno-occlusive disease (VOD) of the liver has been suspected after conventional anti-cancer chemotherapy in children., Methods: To establish the incidence of hepatotoxicity and its relationship with VOD, we analyzed toxicity data obtained on 511 children affected by Wilms tumor and treated according to the SIOP-9 protocol. They all received pre- and postnephrectomy chemotherapy using dactinomycin (AD) and vincristine (VCR) +/- other drugs +/- radiotherapy according to surgical stage and histology., Results: Sixty-four patients suffered at least one episode of hepatotoxicity and 41 satisfied the criteria for a clinical diagnosis of VOD. In this latter group, toxicity occurred during preoperative treatment in 15 patients and was confirmed histopathologically in 9 of the 16 liver biopsies obtained. There was a higher percentage of children aged less than 1 year at diagnosis in the VOD group than in the other patients (24% vs. 11.4%). The degree of liver damage in the younger patients seems important, as suggested by a higher increase in transaminases. VOD developed in 12% of the 68 irradiated children vs. 7% in the non-irradiated group. Statistical analysis showed an increased risk of VOD in younger patients (p < 0.001) and in those receiving radiotherapy (p < 0.001). All patients recovered after 6-180 days using supportive therapy only., Conclusions: (1) 8% of children treated according to the SIOP-9 protocol, developed hepatotoxicity consistent with VOD. Excluding patients who received radiotherapy, the incidence was 6%. These figures are much higher than in earlier reports, though different diagnostic criteria were used. (2) Chemotherapy with AD and VCR seems to be a major cause of VOD. (3) Risk factors are young age and concomitant radiotherapy. (4) VOD does not prejudice positive outcome for these patients.

The incidence of second malignant neoplasms (SMNs) was investigated among 1,988 patients with complete data, enrolled in the SIOP Wilms tumor trials and studies 1, 2, 5, and 6, treated between September 1971 and October 1987. By the end of 1992, eight SMNs were documented, whereas only 1.3 were expected (standardized incidence ratio [SIR] = 4.15; 95% CI = 1.79, 8.17). The risk increases in the first 10 years from diagnosis, while no apparent excess of risk is observed in the subsequent periods. This finding however is difficult to interpretdue to the low statistical power. The cumulative incidence of a second cancer observed at 15 years after Wilms tumor diagnosis was 0.65%. Six SMNs were registered in the cohort of patients treated in the SIOP studies 1, 2 and 5 (999 cases) compared to the two cases observed in the SIOP6 cohort (989 cases). If the suggested reduced incidence of second cancers between SIOP1-5 and SIOP6 patient cohorts is confirmed by longer follow-up, it might reflect changes in the treatment protocols.

We report a case of synchronous bilateral Wilms' tumor in a girl with incomplete Beck-with-Wiedemann syndrome and hemihypertrophy. Multiple small tumors were present in both kidneys. The initial diagnostic biopsy showed stage I monophasic blastematous Wilms' tumor of favorable histology, with multiple perilobar nephrogenic rests (nephroblastomatosis). By flow cytometry, tumor was diploid, with an S-phase fraction of 13.9%. Dactinomycin and vincristine were begun as per the National Wilms' Tumor Study IV (18 week course). After 1 month, only a single small lesion was evident, which persisted unchanged. Excisional biopsy 5 months after beginning chemotherapy showed entirely necrotic tumor but apparently unaltered nephrogenic rests. After completing chemotherapy, the child has done well, with normal renal function and no evidence of disease 3 years after diagnosis. Management of stage V Wilms' tumor is tailored to the individual case, being as conservative as possible to spare renal parenchyma. Given the high incidence of coexisting nephrogenic rests in bilateral Wilms' tumor, careful follow-up is required, as these potentially premalignant rests may resist chemotherapy.

Colorectal carcinoma is one of the most common primary malignancies in adults and occurs in older patients after pelvic radiation. It is rare in children and young adults. We report two cases of colonic adenocarcinoma which were second malignant neoplasms following treatment for early childhood malignancies. One child had Wilms' tumor at 9 months of age treated with preoperative radiation and surgery. He developed radiation colitis and multifocal intestinal adenocarcinomas 42 years later and died with abdominal carcinomatosis. The second child had retroperitoneal embryonal rhabdomyosarcoma at age 1 year and was treated with preoperative radiation, surgery, and chemotherapy. At age 2 years he had radiation colitis; at age 11 years he had rectal adenocarcinoma associated with adenomatous polyps, focal adenomatous change and radiation colitis. Immunohistochemical studies revealed p53 positivity in both adenocarcinomas and in adenomas from the second patient, suggesting that p53 mutation was involved in carcinogenesis. The history of high-dose radiation in early childhood and the multifocal lesions suggest the adenocarcinomas in both patients were second malignant neoplasms, with associated reactive and benign neoplastic and premalignant lesions well documented in one case. These two cases document the phenomenon of early onset of adult type tumors in survivors of childhood cancer and emphasize the need for continued clinical evaluation of patients at risk for second malignant neoplasms.

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 1 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 1. 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.

Adult patients (greater than 18 years), referred to the Royal Marsden Hospital between 1974 and 1990 with embryonal tumours, have been reviewed. The aim of the study was to document the presentation, management and outcome for this group of patients and to compare these parameters with those of tumours of the same histology arising in the paediatric population. The study population consisted of 15 patients with medulloblastoma, 15 with Ewing's sarcoma, three with neuroblastoma, seven with rhabdomyosarcoma and two with nephroblastoma. Actuarial survival, at 5 years, for adults with medulloblastoma was 80%, which compares very favourably with the outcome for children treated over the same time span. In addition, salvage therapy after relapse was in some cases successful. In the Ewing's sarcoma group the outcome was less favourable, with 5-year actuarial survival of 50%. This is disappointing in view of the lack of tumours with poor prognostic features and may be an area in which these tumours differ from those that arise in children. The number of patients with the diagnosis of neuroblastoma, rhabdomyosarcoma and Wilms' tumour was too small for statistical analysis and they are presented as case reports. Embryonal tumours arising in adults provide an opportunity to study clinical behaviour and biology from an extreme standpoint. This may provide useful information with regard to aetiology, natural history and treatment response. The establishment of registers facilitate the collection of relevant data and also offers the opportunity to improve the treatment received by patients with these rare tumours.

The case of a 7-year-old boy presenting at diagnosis with a localized (stage III) Wilms' tumor of favorable histology is presented. Immunocytologic analysis of bone marrow aspirates revealed cells positive for neural cell adhesion molecule (NCAM) and negative for class I major histocompatibility complex (MHC) antigens. These cells were interpreted as deriving from the tumor blastemal component. Postoperatively the child underwent radiotherapy and chemotherapy, and he remains free of disease 12 months after completion of therapy. In patients with nonmetastatic Wilms' tumor at onset, the evaluation of the actual frequency of occult marrow involvement and the assessment of its clinical significance may necessitate further investigation.

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.

Between 1971 and 1992, 42 children (median age = 2 years) with histologically proven Wilms' tumor were evaluated at the Northern Israel Oncology Institute. Most patients were staged according to National Wilms' Tumor Study (NWTS) criteria by which 18 were clinical stage I-II and 24 were III-IV. Combined therapy (surgery, chemotherapy, and radiotherapy) was given with a change to lower dose radiotherapy (< 2,000 cG) after 1981. The pre-1981 group (13 patients) suffered six relapses, most of which were pulmonary, whereas the 1981-1992 group (29 patients) had three relapses. The actuarial 5-year survival rate using Kaplan-Meier tables was 79% for the entire group but 100% for the 1981-1992 group and 38% for the 1971-1980 group. One case of immediate hepatic toxicity and one sudden death, unknown cause, of a patient in remission occurred in the group. Late deleterious effects were seen in five other patients; four had scoliosis and one developed osteoid osteoma of a rib. Despite these encouraging results, the necessity of ongoing monitoring for further long-term toxicities is apparent.

To evaluate the incidence of second malignant tumors in a cohort of subjects previously treated for childhood cancer, we analyzed data from the Off-Therapy Registry (OTR) of the Italian Association of Pediatric Hematology/Oncology, which collects information on children treated for Hodgkin's disease, non-Hodgkin's lymphoma, Wilms' tumor, acute lymphoblastic leukemia (ALL) and acute non-lymphatic leukemia and who had been removed from treatment in the absence of clinical signs of disease, i.e. the off-therapy stage. Second malignant tumors (SMT), diagnosed before December 31, 1988, were identified through a special enquiry to the 36 institutions cooperating in the registry. Observed cases were compared to expected numbers estimated from age- and sex-specific incidence rates derived from the Cancer Registry of the Province of Varese. In a total of 3,310 study subjects, 27 SMTs have been registered. The Cumulative Risk (CR) of SMT was 2.9% 15 years after the end of treatment and the Standard Incidence Ratio (SIR) was 10.8. The ALL sub-cohort had the highest risk of SMT (SIR 13.6) and 9 cases of CNS tumor occurred in this group (SIR 58.9). All 9 had received prophylactic cranial radiotherapy (CRT) and 5 had been treated on one protocol, characterized by low-dose intrathecal methotrexate (IT MTX) given monthly for 2 years after CRT. The Off-Therapy Registry has unique criteria for inclusion; direct comparisons with similar studies are therefore somewhat problematic. However, our data suggest that the risk of SMT in childhood ALL cancer survivors may be greater than previously reported, and that CNS tumors are the most common SMT in this group. The administration schedule of IT MTX may be an important risk factor.

One-hundred-twelve children with pathological diagnosis of Wilms' tumor were treated during the period 1979-1989. They were postoperatively staged as follows: stage I, 25 patients; stage II, 27 patients; stage III, 48 patients; and stage IV, 9 patients. Three patients were preoperatively classified as stage V. The National Wilms' Tumor Study (NWTS) staging system was used. Except for Stage V patients, the treatment regimen consisted of nephrectomy followed by radiotherapy and/or chemotherapy according to stage of disease and pathology. Stage I, II, and III patients with favorable histology enjoyed 94 +/- 6%, 86 +/- 8%, and 71 +/- 8% 10-year actuarial survival, respectively. Stage IV patients and those in stages I, II, and III with unfavorable histology had a 10-year actuarial survival of 36 +/- 8%. Univariate analyses proved that NWTS stages affected the 10-year actuarial disease-free survival rates but not the overall survival rates. The histopathology significantly affected the disease-free survival and the overall survival rates both in the whole group of patients and in each stage when considered separately. The same histopathology also affected the incidence of development of distant relapse but not the local recurrence rate. On the other hand, massive tumor rupture at surgery increased the incidence of local relapse but not of distant metastasis and did not affect the overall survival rates. The presence of residuum after surgery had nearly the same effect as tumor rupture on the local recurrence. It also did not increase significantly the distant relapse incidence, but it affected significantly the overall survival. Retroperitoneal lymph node involvement had a similar effect. It increased the incidence of local relapse and decreased the 10-year overall survival rate but it had a borderline effect on development of distant metastasis (P = 0.06). The age at diagnosis had also a borderline effect on disease-free survival but it had not effect, of statistical significance, on the overall survival.

This survey includes 25 children with Wilms' tumor undergoing high-dose chemotherapy associated with autologous bone marrow transplantation (ABMT) in the period June 1984-December 1991 and enrolled in the European Bone Marrow Transplantation Registry for Solid Tumors. At diagnosis, 12 children presented stage IV disease, 5 stage III, 3 stage II, and 5 stage I. Before ABMT, 21 children had 1 to 4 relapses (median 1); 13 achieved a second or subsequent complete remission (CR), four stage IV children failed to respond to first line treatment and achieved either CR (3 patients), or partial remission (PR) after second line therapy. At high-dose chemotherapy, 17 children were in CR and 8 had measurable disease. Seven different high-dose regimens were administered, even if 20 children received melphalan mostly associated with vincristine and 8 involved field radiotherapy. Three children died early of pneumonitis; 2 developed an acute transient renal failure, 1 a chronic renal failure. Out of the 8 children with target disease at graft, 2 died of toxicity, 5 achieved CR, 1 obtained PR, and only 1 is presently alive in CCR at 39 months after ABMT. Of the 17 children grafted in CR, 8 are alive event-free at 14-90 months (median 34) from ABMT; 7 relapsed at 3-23 months (median 7 months); 1 died of toxicity and 1 was lost to follow-up in CR at 12 months. A salvage attempt with high-dose chemotherapy in children with resistant or poor prognosis recurrent Wilms' tumor seems to be justified. An international cooperative protocol taking into account the increased risk of lung and renal toxicity is necessary.

In the United States, the initial morphologic diagnosis of nephroblastoma is usually determined on a nephrectomy specimen prior to the initiation of any additional therapy. Such an approach, however, is not appropriate in all children; we believe that fine-needle aspiration biopsies (FNAB) should be the initial diagnostic procedure in a minority of patients with suspected Wilms' tumor. One such group of patients is those who present with stage IV disease, especially when it is considered unresectable. Herein we present two children with advanced Wilms' tumor to support our contention. The initial microscopic diagnosis in each was made by FNAB. Following chemotherapy, predominantly necrotic Wilms' tumors were excised. Both patients are alive with no evidence of residual disease or untoward affects from the aspiration procedure.

The epidemiological and clinical features of Wilms' tumor (WT) were analyzed in 176 patients admitted to the Brazilian WT Study Group. The occurrence of congenital anomalies (9.1%) and the M:F ratio (0.83) were comparable to those observed by the US National WT Study and the International Society of Pediatric Oncology trials. Bilateral cases were younger on average than unilateral cases (37.2 vs. 45.0 months). Ethnic group and gender were also associated with age, with non-white children being generally older (46.1 months) than whites (39.5 months), and boys being younger than girls (37.0 vs. 46.1 months). However, the most important factor in association with age at diagnosis was disease stage. No early disease patients were diagnosed after 8 years of age (mean: 37.5 months), whereas 10% of those with advanced disease were diagnosed between the ages of 8 and 10 years (mean: 56.3 months). There were no clear distinctions in age distributions on the basis of the presence of tumor multicentricity, intra- or perilobar nephroblastomatosis, and of a combination of putative genetic determinants. The mean age at diagnosis for cases with congenital defects was higher than that for the remaining patients. Some of the study results are in support of the recessive oncogene model for WT. However, the possible confounding effect of disease stage and the strong interdependence of the remaining factors may be masking important relations in regard to mutational events occurring during embryogenesis.

A patient is described who developed Hodgkin's disease 16 years after treatment of Wilms' tumor with radiation and actinomycin D. The issues relating to Hodgkin's disease as a second malignancy are reviewed. The need for long-term surveillance of patients with malignant disease for late effects of the cancer and its treatment is emphasized.

We performed routine computerized tomography (CT) of the chest and abdomen on patients treated for Wilms' tumor and reviewed the records of all patients who relapsed (10 patients) and 43 additional patients followed for at least 1 year. Routine chest radiographs and abdominal ultrasounds were compared with 210 CT examinations (107 chest and 103 abdomen). CT examinations were obtained at 6 months for stage I (13 patients) and at 3, 8, and 15 months for stages II, III, and IV (40 patients). Of the 10 patients who relapsed, only 2 were documented by CT scan in the absence of clinical symptomatology and presence of normal radiographs and ultrasound. Eight relapses were diagnosed by physical examination, chest radiograph, or ultrasound and confirmed by CT scan. Questionably abnormal CT scans were obtained in 7 patients, only 1 of whom eventually relapsed. Since only 2 of 210 routine CT examinations were the the only indicator of relapse, we conclude that the routine use of CT for follow-up in Wilms' tumor is not warranted.

A seven-year-old boy had cardiac symptoms for five months before the diagnosis of Wilms tumor was made. The tumor extended into the inferior vena cava through the renal vein and protruded into the right atrium. All demonstrable tumor masses could be removed at a one-step surgical procedure without using cardiopulmonary bypass. Intensive postoperative chemotherapy has been given, and 15 months after surgery he was without signs of relapse.

Despite the tremendous progress that pediatric oncology has achieved in the treatment of Wilms' tumor over the last several decades, survival rates in our institution before 1970 did not exceed 8%. In order to correct the problem standardized therapy was instituted in 1970 through a multimodal oncological team. Results using the new approach were reviewed in 1979 (50 patients) and showed an overall 34% 2-year survival rate. Although encouraging, these results were still far below the ones reported in the literature. This prompted us to use a vigorous professional and lay educational program in the city. Treatment methods were replaced by those advocated by the Second National Wilms' Tumor Study. A second evaluation period initiated in 1979 and extended through 1984 (35 patients) yielded an overall 83% survival rate. A retrospective study of the two periods by univariate and multivariate survival analysis revealed that, although much of the improvement in survival could be attributed to a shift in stage distribution towards earlier disease, the admission period itself had an important additional explanatory effect with respect to survival. This was probably due to the improvement in treatment protocols used in the latter period. Age was a prognostic variable only for patients admitted during the 1979-1984 period.

Before 1969, 58 patients with Wilms' tumors treated at Children's Hospital of Buffalo had an all-stage survival of 57%. From 1970 to 1983, following the National Wilms' Tumor Study protocols, this survival rate has improved to 79% in the last 47 patients. With continued attention toward early diagnosis, accurate and complete staging, refinement of radiation and chemotherapy protocols, and absolute follow-up of all patients, the relapse-free survival rate will continue to improve.

A 63-year-old man had an unresectable metastatic Wilms tumor in the right kidney. Radiotherapy to the abdomen and chest wall as well as chemotherapy in the form of actinomycin D, vincristine, and cyclophosphamide was given. The tumor was radioresponsive but failed to respond to chemotherapy. The literature was reviewed. Other reported cases of Wilms tumor in adults treated with chemotherapy that is usually given to children are few, but the results are mostly disappointing.

Two well-documented cases of Wilms' tumor in adult patients are reported. Surgery remains the treatment of choice in stage I cases with favorable cell differentiation. Adjuvant therapy with chemotherapy or radiation may be necessary in patients beyond stage I or when the cell differentiation is more anaplastic. Actinomycin D is essential and should be included in the chemotherapeutic regimen whenever it is possible.

A six-year-old girl presented with clinical signs and symptoms of right-sided heart failure. Cardiac catheterization demonstrated filling defects in both pulmonary arteries felt to represent metastatic lesions or thromboemboli. Intravenous pyelogram revealed bilateral renal masses and intrarenal obstruction. Acute renal failure was unresponsive to standard therapy. An open renal biopsy revealed Wilms tumor with favorable histology. Aggressive chemotherapy and irradiation were undertaken and renal function returned. This case adds to the heterogeneity of presentations described for Wilms tumor, and review of the literature reveals no other cases with similar presenting signs.

Eighty-six children were diagnosed with cancer in infancy, followed for at lest 5 years, and assessed for late effects of disease and therapy. One child subsequently died from respiratory failure and 3 died from second primary cancers. Another patient survived second primary cancers of the skin. The high frequency of new cancers (4 observed, 0.09 expected) was attributable to host susceptibility factors and treatment effects. Kyphoscoliosis was diagnosed in 44 patients, 40 of whom had received radiotherapy to the spine. Other patients had neurologic deficits, pulmonary fibrosis, hypoplastic breasts, bowel adhesions, thyroid nodules, musculoskeletal defects, and liver fibrosis associated with tumor therapy. Sequelae of cancer were more common after treatment in infancy than in later childhood. Improved treatments and knowledge of natural history can reduce adverse effects of therapy.