Survival assessment of nephron-sparing surgery or radical nephrectomy in children with unilateral Wilms tumor receiving adjuvant chemotherapy: a retrospective cross-sectional study.

OBJECTIVE: Surgical treatment of unilateral Wilms tumor (WT) in children is controversial. In this study, we aimed to evaluate the survival and prognosis of radical nephrectomy (RN) and nephron-sparing surgery (NSS) in children with unilateral WT receiving adjuvant chemotherapy. PATIENTS AND METHODS: Data on pediatric patients with WT were collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Multivariate logistic regression was used to analyze factors influencing the choice of surgical strategy. Cox proportional hazard models were used to assess factors associated with overall survival. RESULTS: We included 1,825 patients with unilateral WT (<14 years) who received adjuvant chemotherapy and surgery. Between 2000 and 2019, the percentage of patients treated with NSS increased from 4% in 2000 to 8% in 2019. There was no significant difference in 10-year overall survival between the two surgical strategies [NSS vs. RN, 93.26% (95% CI, 86.88%-100%) vs. 92.17% (95% CI, 90.75%-93.61%), p=0.98]. Patients with unilateral WTs ≤4 cm were more likely to be treated with NSS. There was no survival benefit for patients treated with RN compared with that for those treated with NSS (HR, 0.74; 95% CI, 0.29-1.86; p=0.5). CONCLUSIONS: The use of NSS in children with unilateral WT has increased over the last two decades. Tumor size is an important influencing factor for the surgical application of NSS. Patients who underwent NSS had an equivalent OS compared with the overall group of patients with unilateral tumors who received RN.

Diffusion-weighted MRI and histogram analysis: assessment of response to neoadjuvant chemotherapy in nephroblastoma.

PURPOSE: To assess the value of diffusion-weighted MRI (DW-MRI) in the non-invasive prediction of blastemal remnant after neoadjuvant chemotherapy in nephroblastoma. METHODS: This IRB-approved study included 32 pediatric patients with 35 tumors who underwent DW-MRI prior and after completion of neoadjuvant chemotherapy and subsequent surgical resection. Two blinded radiologists volumetrically assessed each tumor on pre- and post-neoadjuvant images and the parameters mean ADC, median ADC, 12.5th/25th/75th ADC percentile, skewness, and kurtosis were calculated. Blastemal remnant was determined per the pathology report. Associations between imaging features and blastemal remnant quartiles were examined using the Kruskal-Wallis test and adjusted for false discovery rate. RESULTS: Inter-reader agreement was high for mean ADC, skewness, kurtosis, and volume (ICC: 0.76-0.998). Pre-therapeutic histogram parameters skewness and kurtosis were found to be higher in patients with a higher amount of blastemal remnant for reader 1 (overall p = 0.035) and for kurtosis in reader 2 (overall p = 0.032) with skewness not reaching the level of statistical significance (overall p = 0.055). Higher tumor volume on pre-treatment imaging was associated with a higher amount of blastemal remnant after therapy (overall p = 0.032 for both readers). CONCLUSIONS: Pre-treatment skewness and kurtosis of ADC histogram analysis were significantly associated with a larger fraction of a blastemal remnant after neoadjuvant chemotherapy. These findings could be incorporated into a more personalized chemotherapeutic regime in these patients and offer prognostic information at the time of initial diagnosis.

Assessment of somatic mutations in urine and plasma of Wilms tumor patients.

Tumor DNA has been detected in body fluids of cancer patients. Somatic tumor mutations are being used as biomarkers in body fluids to monitor chemotherapy response as a minimally invasive tool. In this study, we evaluated the potential of tracking somatic mutations in free DNA of plasma and urine collected from Wilms tumor (WT) patients for monitoring treatment response. Wilms tumor is a pediatric renal tumor resulting from cell differentiation errors during nephrogenesis. Its mutational repertoire is not completely defined. Thus, for identifying somatic mutations from tumor tissue DNA, we screened matched tumor/leukocyte DNAs using either a panel containing 16 WT-associated genes or whole-exome sequencing (WES). The identified somatic tumor mutations were tracked in urine and plasma DNA collected before, during and after treatment. At least one somatic mutation was identified in five out of six WT tissue samples analyzed. Somatic mutations were detected in body fluids before treatment in all five patients (three patients in urine, three in plasma, and one in both body fluids). In all patients, a decrease of the variant allele fraction of somatic mutations was observed in body fluids during neoadjuvant chemotherapy. Interestingly, the persistence of somatic mutations in body fluids was in accordance with clinical parameters. For one patient who progressed to death, it persisted in high levels in serial body fluid samples during treatment. For three patients without disease progression, somatic mutations were not consistently detected in samples throughout monitoring. For one patient with bilateral disease, a somatic mutation was detected at low levels with no support of clinical manifestation. Our results demonstrated the potential of tracking somatic mutations in urine and plasma DNA as a minimally invasive tool for monitoring WT patients. Additional investigation is needed to check the clinical value of insistent somatic mutations in body fluids.

Volumetric assessment of unaffected parenchyma and Wilms' tumours: analysis of response to chemotherapy and surgery using a semi-automated segmentation algorithm in children with renal neoplasms.

OBJECTIVE: To present our proof of concept with semi-automatic image recognition/segmentation technology for calculation of tumour/parenchyma volume. METHODS: We reviewed Wilms' tumours (WTs) between 2000 and 2018, capturing computed tomography images at baseline, after neoadjuvant chemotherapy (NaC) and postoperatively. Images were uploaded into MATLAB-3-D volumetric image processing software. The program was trained by two clinicians who supervised the demarcation of tumour and parenchyma, followed by automatic recognition and delineation of tumour margins on serial imaging, and differentiation from uninvolved renal parenchyma. Volume was automatically calculated for both. RESULTS: During the study period, 98 patients were identified. Of these, based on image quality and availability, 32 (38 affected moieties) were selected. Most patients (65%) were girls, diagnosed at age 50 ± 37 months of age. NaC was employed in 64% of patients. Surgical management included 27 radical and 11 partial nephrectomies. Automated volume assessment demonstrated objective response to NaC for unilateral and bilateral tumours (68 ± 20% and 53 ± 39%, respectively), as well as preservation on uninvolved parenchyma with partial nephrectomy (70 ± 46 cm3 at presentation to 57 ± 41 cm3 post-surgery). CONCLUSION: Volumetric analysis is feasible and allows objective assessment of tumour and parenchyma volume in response to chemotherapy and surgery. Our data show changes after therapy that may be otherwise difficult to quantify. Use of such technology may improve surgical planning and quantification of response to treatment, as well as serving as a tool to predict renal reserve and long-term changes in renal function.

Fifteen-minute consultation: Assessment, surveillance and management of hemihypertrophy.

This article aims to provide a structured and concise guide for the general paediatrician managing a child with hemihypertrophy. Hemihypertrophy is a relatively uncommon condition. The significance is that a proportion of those affected are at risk of developing malignancies in childhood. For these children regular surveillance is required. We have outlined how one might assess and investigate a child presenting with hemihypertrophy. We have also formulated a practicable surveillance strategy which is in line with the current Royal College of Paediatrics and Child Health (RCPCH) guideline 'Wilms' tumour surveillance in at-risk children'.

Childhood cancer in Gondar University Hospital, Northwest Ethiopia.

BACKGROUND: Childhood cancer becomes a public health problem in developing countries which aggravates the burden of childhood mortality by infectious diseases and malnutrition. In poor countries, the death rate for most pediatric cancers is almost 100%. This study attempts to determine the magnitude, patterns and trends of pediatric malignancies in the study area which is important in re-evaluating existing services and in improving facilities and patient care. METHODS: A retrospective study of 3 year period were carried out among all children aged below 15 years old admitted into the pediatric wards of Gondar University Hospital, Northwest Ethiopia. The charts of all children aged below 15 years old admitted in the pediatric wards due to cancer were reviewed by using the data collection format. Data were entered and analyzed using SPSS version 20 statistical package. RESULT: A total of 71 cancer cases were diagnosed and admitted to the pediatrics ward during the study period. More than two-third of the study subjects 50 (70.4%) were males. The mean age of study subjects was 7 ± 4 year where majority 26 (36.6%) of the study subjects were ≥10 years. Of all, 43 (60.6%) were hematological malignancy followed by Wilms tumor 13 (18.3%), Neuroblastoma 5 (7%), Rhabdomyosarcoma 3 (4.2%), Brain tumor 3 (4.2%), Hepatoblastoma 2 (2.8%). More than two-third of cases were found to be concomitantly malnourished being stunted, wasted and under weight. Nearly half of patients had not received chemotherapy and majority of those started chemotherapy did not complete all the treatment cycles. Shortage and absence of safe and affordable chemotherapy drugs were the major reasons for therapy interruption. CONCLUSION: The study shows increasing childhood cancer cases over the years. Hematological malignancy takes the leading prevalence followed by Wilms tumor and Neuroblastoma. The majority of cases were also discharged without any clinical change that had the only death option. Therefore, the government and the hospital should give emphasis to establish cancer therapy centers and insure accessibility and affordability of chemotherapy drugs.

Use of 18F-FDG-PET-CT for Assessment of Response to Neoadjuvant Chemotherapy in Children With Wilms Tumor.

PURPOSE: The aim of this study was to evaluate the predictive value of fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (F-FDG-PET-CT) in the assessment of histologic response to neoadjuvant chemotherapy in children with Wilms tumors (WTs). MATERIALS AND METHODS: We prospectively registered 12 patients with WTs who were treated with 2 cycles of neoadjuvant chemotherapy and surgery. All patients underwent sequential F-FDG-PET-CT before (PET-CT1) and after (PET-CT2) neoadjuvant chemotherapy. Maximum standardized uptake value (SUVmax) was measured on PET-CT1 (SUV1) and PET-CT2 (SUV2). The percentage change in SUVmax (SUVmax reduction) was calculated. After surgery the effects of neoadjuvant chemotherapy were graded histopathologically: ≥90% necrosis indicated a good response and <90% necrosis was considered a poor response. The correlation between SUVmax reduction and histologic response was estimated using the Spearman correlation coefficient. RESULTS: Among the 12 patients who underwent PET-CT before and after chemotherapy, SUVmax reduction was significantly different between the good response group and the poor response group (P=0.035). A significant, in terms of P value, correlation was found between pathologic response and SUVmax reduction (r=0.700; 95% confidence interval, 0.060-0.935; P=0.011). A threshold of 66% reduction in SUVmax was identified, with which partition, there were 8 good histologic responders (≥66% decrease in SUVmax) and 4 poor responders. The histologic complete response rate of the good responders was 87.5%, whereas that of poor responders was 0%. SUV1≥7 and SUV2≥2.4 were both considered to be with high risk of recurrence. In patients with SUV1≥7, 4/5 cases relapsed and 4/6 patients with SUV2≥2.4 relapsed. CONCLUSIONS: As there seems to be a good correlation of changes in SUVmax and histologic response, PET-CT has the potential of predicting the response to neoadjuvant chemotherapy in children with WT. SUV1 and SUV2 by themselves might be a good prognosticator of the clinical outcome of WT pediatric patients treated with International Society of Pediatric Oncology protocols, although the reduction rate of SUVmax is much less powerful for prognosis.

The Collaborative Wilms Tumour Africa Project; baseline evaluation of Wilms tumour treatment and outcome in eight institutes in sub-Saharan Africa.

AIM: Reported survival of Wilms tumour in sub-Saharan Africa is below 50%. A published International Society of Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) consensus adapted treatment guideline is implemented as a multi-centre prospective clinical trial at eight centres in sub-Saharan Africa. A baseline evaluation has been done to help decide on priorities to improve outcome and to assess improvements over time. METHODS: A retrospective chart review was performed of patients admitted with Wilms tumour in the three years (2011-2013) preceding the collaborative trial. Patient outcome at the end of treatment was documented for all patients diagnosed in 2011 and 2012. Outcome was classified as (1) alive, no evidence of disease; (2) alive with disease; (3) died during treatment and (4) incomplete treatment. Details on treatment facilities, staff and estimated cost of treatment are documented. RESULTS: Every year 114-130 patients are diagnosed. The mean survival at end of treatment is 39% (69/176) ranging from 11% to 61%. Incomplete treatment is the most common cause of treatment failure with 31% (54/176), ranging from 14% to 48% between centres. Twenty-six percent (46/176) of patients died during treatment, ranging from 13% to 37%. Estimated cost of treatment for parents ranged from 100 US$ to 1100 US$ and was considered an important cause of failure to complete treatment. CONCLUSION: Overall two year survival is estimated at 25%. Prevention of incomplete treatment is possible and will positively affect outcome. Sharing similar local challenges in this regional collaborative project helps to identify and implement feasible, sustainable and successful strategies.

Potential role of PET-CT in chemotherapy efficacy assessment and recurrence diagnosis in a patient with a Wilms' tumour.

BACKGROUND: Wilms' tumour is the most frequent renal malignancy in children. There is no worldwide consensus regarding treatment and PET-CT role in this neoplasm. The aim of this report is to demonstrate the potential role of PET-CT in chemotherapy efficacy assessment and recurrence diagnosis. CASE DESCRIPTION: a 7-year-old boy was diagnosed with blastemic type Wilms' tumour and underwent neoadjuvant chemotherapy, nephrectomy, and adjuvant chemotherapy in compliance with SIOP protocol. Three years later the patient underwent surgical resection of the metastasis and chemoradiotherapy. Nine months later tomography and PET-CT were performed (during the third month of the treatment due to a second recurrence). The results were equivocal but within four months the boy underwent surgical resection of a third recurrence. Fourteen months later a second PET-CT revealed an active disease with extensive involvement of the left lung and pleura. The patient was referred to oral palliative chemotherapy. DISCUSSION: Equivocal PET-CT results during chemotherapy should be interpreted with caution. The first, during third line chemotherapy, was equivocal; however, an early massive recurrence three months later indicates that treatment was ineffective. The second PET-CT examination fourteen months later, as the only modality, depicted massive progression of the disease. This suggests the value of this examination in recurrence diagnosis. CONCLUSIONS: PET-CT seems to be valuable technique in recurrence detection in patients with histologically unfavourable tumours. Equivocal results of PET-CT should raise suspicion of recurrence even in recently treated patients. The timing of CIM and PET-CT should be considered individually--no universal and reliable schedule exists.

Children treated with metronomic chemotherapy in a low-income country: METRO-MALI-01.

BACKGROUND: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. As off-patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach, MC seems to be well adapted to low-income countries. OBJECTIVE: The aim of this study was to assess the efficacy and safety of a vincristine/cyclophosphamide/methotrexate MC regimen given to children with refractory cancer of various tumor types. METHODS: This prospective, pilot, single-center study evaluated the use of MC with a first cycle consisting of weekly vincristine (1.5 mg/m) on days 1, 8, 15, and 22, daily cyclophosphamide (25 mg/m) on days 1 to 21, and twice weekly methotrexate (15 mg/m) on days 21 to 42, followed by a 1-week break. For the following cycles, vincristine was administered only at weeks 1 and 5 of the cycle. This treatment was proposed to children with refractory cancer following treatments with the standard protocols available in our institution and to patients who were not eligible for the protocol. Adverse events were determined through laboratory analyses and investigator observations. RESULTS: From November 2008 to December 2009, 12 children (median age, 3.7 y; range, 2 to 7 y) were included. The most frequent diagnoses were Wilms tumors (6) and retinoblastoma (5). No objective response was observed, but 7 patients experienced disease stabilization (58%) and continued their treatment for 15 to 24 weeks. After a median follow-up of 39 weeks, 6 patients (50%) were alive. Most importantly, in 3 patients (25%), disease remained stable for at least 6 months after completion of treatment. One grade 4 anemia was observed in 1 patient and 1 grade 4 nonfebrile neutropenia in 1 patient. No other grade 3 or 4 toxicities were noted. CONCLUSION: The MC regimen that we report here was well tolerated and was associated with disease stabilization. Most importantly, stabilization could be maintained for over 6 additional months after completion of treatment in 3 patients. The potential of MC in children and young adults in low-income countries warrants further studies.

Decision analysis to compare treatment strategies for Stage I/favorable histology Wilms tumor.

BACKGROUND: Decision analysis was used to clarify differences in survival and complication rates comparing surgery alone versus surgery plus chemotherapy for Stage I, favorable histology Wilms tumor patients. PROCEDURE: A state transition model was used to simulate treatment with nephrectomy-only, nephrectomy with adjuvant vincristine (VCR) or with vincristine plus dactinomcyin (NWTS Regimen EE4A). Rates of relapse and complications of therapy were obtained from the literature. In sensitivity analysis, the model was probed for the value(s) at which the treatment of choice changes. RESULTS: The overall survival (OS) is essentially the same for patients treated with any of the three strategies (OS(Nephrectomy) = 98.8%; OS(EE4A) = 98.8%; OS(VCR) = 98.6%). Rates of serious long-term complications in the surviving population are also similar across treatment strategies (nephrectomy = 1.4%; VCR = 1.2%; EE4A = 0.3%). Both the progression and salvage rates after nephrectomy-only would have to be much worse than expected for nephrectomy-only to be an unacceptable strategy. CONCLUSIONS: The differences in overall survival and rates of long-term complications between the three different initial strategies were negligible in the model. Based on this analysis, it was decided by the Children's Oncology Group that it was acceptable to continue to include nephrectomy without adjuvant chemotherapy as an experimental arm of the low risk Wilms tumor protocol with stringent eligibility criteria and close follow-up. Decision analysis can have a role in clinical trial design by making the tradeoffs between strategies more explicit. The robustness of these conclusions can be tested by widely varying the underlying assumptions.

Role of CT in assessment of unresectable Wilms' tumor response after preoperative chemotherapy in pediatrics.

The purpose of this study was to define the structural response of unresectable Wilms' tumor following preoperative chemotherapy by computed tomography (CT). We also compared CT changes in relation to histopathological nature. The study included 36 patients with 41 nephroblastomas. All were examined by CT before preoperative chemotherapy using multiphasic CT protocol study. The unresectability was diagnosed by CT imaging. All patients were subjected to fine-needle biopsy (FNB) to confirm the diagnosis and to define the histopathological type before preoperative chemotherapy. Five patients had unfavorable pathology and 31 patients with 36 nephroblastomas had favorable pathology. All patients received first line of treatment. Follow-up of these patients by CT at the 6th week was reviewed. All of our patients were diagnosed as unresectable Wilms' tumor by CT. Preoperative chemotherapy was started. Among our patients, 28 (77.8%) gave good response in the form of significant reduction in tumor size, disappearance of one tumor in two cases with bilateral WT and inferior vena cava (IVC) thrombus, and increased nonenhancing necrotizing content. Two patients with unfavorable pathology did not show any response. The remaining six patients gave partial response. CT can be used to evaluate tumor response and resectability after preoperative chemotherapy with high accuracy. The response to preoperative chemotherapy is not related to the histopathological classifications.

Assessment of oral complications in children receiving chemotherapy.

The aim of this study was to assess the early oral complications in pediatric patients receiving chemotherapy. An interview and oral examination was conducted on 150 pediatric cancer patients receiving standard dose chemotherapy. Results showed that oral pain and dry mouth were the most frequent patients' complaints. The prevalences of chemotherapy-induced oral mucositis and oral infections were relatively high. The chemotherapeutic antimetabolites were the most frequently associated with oral complications than other types of chemotherapy. The present results indicate that the oral complications among patients receiving chemotherapy are common.

Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of the administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 905 previously untreated children aged younger than 16 years with stage II favorable histology (FH) WT (low-risk [LR]), stages III to IV FH WT, or stages I to IV clear-cell sarcoma of the kidney (high-risk[HR]) were randomized after the completion of 6 months of chemotherapy to discontinue (short) or continue for 9 additional months (long) treatment with chemotherapy regimens that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either divided-dose (STD) courses (3 days) or single-dose (PI) treatment with doxorubicin. RESULTS: The 4-year relapse-free survival (RFS) rates after the second randomization for LR patients were 83.7% for the 190 patients treated with short and 88.2% for the 187 patients treated with long chemotherapy (P = .11). The 4-year RFS rates after the second randomization for HR FH patients were 89.7% for the 256 patients treated with short and 88.8% for the 246 patients treated with long chemotherapy (P = .87). The charge for treatment with the short PI treatment regimens for all children with stages I through IV FH WT was approximately one half of that with the long STD treatment regimens. CONCLUSION: The short administration schedule for the treatment of children with WT is no less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.

[Assessment of the resectability of Wilms' tumors in childhood]. / Beurteilung der Resektabilität von Wilmstumoren im Kindesalter.

Over the last ten years 62 children were operated for renal tumours. The therapeutic aim in Wilms' tumours is complete macroscopic resection of the primary tumour, assessing resectability as accurately as possible. Overestimating surgical possibilities may lead to intraoperative rupture of the tumour (three cases), while overestimating local tumour extent may result in too much preoperative chemotherapy, which resulted in the life-threatening complication of venous occlusive disease of the hepatic veins (VOD) in three infants. The assessment of resectability may become particularly problematic in bilateral (six cases) or multifocal Wilms' tumours (two cases), and in nephroblastomatosis (two cases), i.e. the persistence of embronal renal tissue, a facultatively precancerous lesion, which requires quarterly sonographic controls and which induced a second metachronous contralateral Wilms' tumour in one child.

National Wilms' Tumor Study: economic perspective.

The National Wilms' Tumor Study poses a question of an essentially economic nature: Can the socioeconomic impact of therapy for Wilms' tumor on the patient's family and society be lessened without compromising the efficacy of therapy? But the only proposed measure of socioeconomic impact appears to be the extent of hospitalization. From an economic perspective, more information is ideally needed from the trial to establish the magnitude of any difference in effectiveness and the magnitude of the difference in costs, so that any trade-off between the two can be assessed. In practice, the extent of the economic data needed at the end of the study will depend on the clinical outcome results and, hence, the nature of the trade-off that will have to be made. If the less extensive treatment is found to be ineffective, economic issues will not come into play. Similarly, if the less extensive treatment is clearly superior in every clinical aspect, the argument for it will probably be persuasive. The interesting situation of a trade-off arises if the less extensive treatment offers clear socioeconomic advantages but has some small clinical disadvantage. In that case, the extent and nature of an array of socioeconomic factors will need to have been measured, not just presumed. There are, of course, many problems associated with collecting and analyzing more comprehensive socioeconomic data in a long trial. This article considers a number of these problems and focuses on six important issues in designing the necessary economic components of future trials.

Relationship between dose schedule and charges for treatment on National Wilms' Tumor Study-4. A report from the National Wilms' Tumor Study Group.

National Wilms' Tumor Study-4 was designed to evaluate the efficacy, toxicity, and cost of administration of different regimens for the treatment of Wilms' tumor. The charges for treatment with dactinomycin and doxorubicin administered by two different schedules were calculated using current charges in Buffalo, N.Y. An annual savings of approximately $779,259 could be achieved by the use of the short, pulse-intensive (i.e., single-dose) treatment regimens for all children with Wilms' tumor of stages I-IV/favorable histology. The pulse-intensive administration schedule for the treatment of children with Wilms' tumor permits administration of chemotherapy at a substantially lower total treatment cost.

Assessment of proliferative activity in Wilms' tumour.

The proliferative activity in 26 cases of Wilms' tumour was studied by enumeration of silver-staining nucleolar organizer regions (AgNORs) and proliferating cell nuclear antigen (PCNA) staining of the blastemal, epithelial and stromal components of the tumours. The PCNA and AgNOR scores derived from the blastemal (PCNA range 18.9-81.4%, AgNOR range 2.11-4.95) and epithelial (PCNA range 24.1-74.2%, AgNOR range 2.47-4.41) components of the tumours were significantly higher than those of the stromal component (PCNA range 3.4-64.7%, AgNOR range 2.20-4.26). Ten of the patients had died with recurrent or metastatic tumour (mean survival 29 months) while the remaining 16 were disease free (mean follow-up 95 months) at the time of the study. The prognostic significance of PCNA and AgNOR for Wilms' tumour was evaluated by dividing the tumours into groups exhibiting low (PCNA < or = 40 or AgNOR < or = 4) or high (PCNA > 40 or AgNOR > 4) proliferative activity. There was a significant difference in the survival of the two groups for tumours treated with preoperative chemotherapy (PCNA, P = 0.049; AgNOR, P = 0.02), while no significant difference was observed from tumours resected prior to the administration of chemotherapy. The results of this study suggest that assessment of proliferation activity in postchemotherapy Wilm's tumours may be a useful indicator of prognosis.