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Background: Studies describing intravascular involvement in Wilms tumor have focused on illustrating individual institutional experience and the elements of surgical management. Thrombus characteristics like extent, patterns of regression, and correlation with the surgical findings, intraluminal adhesion, and viable tumor in the thrombus, and patency of the inferior vena cava (IVC) have not been systematically described., Objectives: The aim of this study is to evaluate these thrombus characteristics and explore their impact on the overall outcomes., Methods: All patients with histologically confirmed Wilms tumors with intravascular thrombus diagnosed in the pediatric oncology unit of Tata Memorial Hospital registered from 2006 to 2019 were included. Data regarding clinical, radiological, and surgical particulars were retrieved from the prospectively maintained institutional database. Specific data for the thrombus included: distal extent before and after neoadjuvant chemotherapy, correlation of extent with the surgical findings, completeness of thrombectomy, the presence of a viable tumor in the thrombus, and the patency of the IVC. Survival analysis was performed utilizing the Kaplan-Meier method on SPSS software version 25., Results: The study included 43 (9.9%) of the 432 patients with Wilms tumor having intravascular extension. Retrohepatic IVC (33.3%) followed by atrioventricular (26%) formed the frequent levels of thrombus with maximum regression occurring after chemotherapy in the latter (Summary figure). The overall concordance rate between computed tomography (CT) scan and surgical findings for the presence of thrombus was 86% and 4 patients had the thrombus limited to a lower level than the preoperative scan. At a median follow-up of 5-years, the 5-year event-free and overall survival was 81% and 82.2% respectively. Atrioventricular thrombus (p = 0.003) and postoperative patency of IVC (p = 0.02) were significantly associated with inferior survival, while the extent of regression, thrombus fracture, and viability was not significant., Discussion: The findings of this study bring forth the characteristics of intravascular tumor thrombus affecting the outcomes which can be validated in future prospective studies. Although the ideal method for radiological assessment of the intravascular thrombus is elusive, CT scan provided adequate information for the presence and level of the intravascular thrombus with reasonable accuracy in this study. Study limitations include small sample size, the limited number of events, and lack of multivariate analysis to rule out confounding factors that could influence the observed findings., Conclusion: Atrioventricular thrombus and occlusion of IVC represent adverse prognostic factors. The extent of regression, fracture, and viability of thrombus did not affect survival in this study., Competing Interests: Conflicts of interest None of the authors has any conflict of interest., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Nephroblastoma or Wilms tumor, a common embryonal tumor in children, can occasionally occur in adults. The survival of patients older than 18 years is reported to be significantly inferior to that of pediatric patients. Establishing a diagnosis for these rare tumors can be challenging for both clinicians and pathologists, who are not accustomed to considering Wilms tumor as a potential differential in adults. This leads to misdiagnosis and a subsequent delay in the initiation of appropriate therapy. The standard of care is not well established for Wilms tumors in adults. We provide here a comprehensive review of the international literature on the subject with the current management protocols in France. We also propose the need of strong inter-disciplinary collaboration between surgeons, pathologists, and medical and pediatric oncologists for increasing knowledge and formulating treatment strategies for these rare tumors. Homogenous guidelines for treating adults with Wilms tumors have been proposed for all patients in France., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Pediatric extrarenal Wilms tumor (ERWT) is rare. The diversity of clinical characteristics makes diagnosis, treatment and judging the prognosis difficult. Long-term follow-up outcomes and the possible prognostic factors of ERWT are still insufficient., Objective: To identify the characteristics, therapeutic strategies and long-term results of pediatric ERWT., Patients and Methods: All children with ERWT in our institution were retrospectively reviewed. The National Wilms Tumor Study (NWTS) system was used to evaluate tumor grade., Results: Among the 876 patients with Wilms tumor in our institution between January 1986 and July 2018, 5 (0.57%) patients had ERWT. Of the 5 children with ERWT, the locations were the retroperitoneum in 3 patients (including 1 presacral) and the gubernaculum testis of an undescended testis and a duplicate sigmoid colon in 1 patient each. Two patients were stage II, and 3 patients were stage III. The three patients with larger tumor sizes had preoperative tumor rupture. In the long-term follow-up, ranging from 1.0 to 10.8 years, 3 patients had disease-free survival, and 2 patients with older age, a larger tumor size and preoperative tumor rupture had recurrence with metastasis, including 1 death., Discussion: Wilms tumor extremely rarely originates outside the kidney. The current case series represents the first report of ERWT accompanied by a duplicate sigmoid colon. ERWT can coassociate with congenital gastrointestinal and genitourinary system anomalies, such as undescended testis and duplicate sigmoid colon, which provide clues to the preoperative diagnosis of ERWT. Deep and not easily palpated locations for the ERWT and older ages were associated with diagnosis delay, which can lead to enlargement of the tumor, an increased risk of preoperative tumor rupture and advancement of the tumor stage. Although only 3% of ERWT cases were metastatic according to previous reports, 2 of 5 patients (patients 1 and 4) with older age, larger tumor size and preoperative tumor rupture had recurrence and metastases in the current study. Thus, patients with poor prognoses often require aggressive combination treatments, and more attention is needed in terms of the recurrence, metastases and fatality of ERWT., Conclusion: ERWTs are rare tumors and can coassociate with congenital gastrointestinal and genitourinary system anomalies. The prognosis of ERWT is comparable to that of Wilms tumor located at normal anatomical sites., Competing Interests: Conflicts of interest None., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction: Non-Wilms renal tumors represent a compelling subset of childhood renal tumors. However, their relative rarity renders accurate diagnosis, and therapy challenging which in some instance is inferred from their adult counterparts., Objective: To describe the incidence and analyze the diagnostic challenges, therapies and, outcomes of non-Wilms renal tumors at the largest tertiary cancer centre in India., Methods: All patients with histologically confirmed non-Wilms renal tumours diagnosed in the paediatric oncology unit of Tata Memorial Hospital between 2006 and 2019 were included. Data regarding clinical and radiological features and treatment outcomes were retrieved from the prospectively maintained institutional database. At the outset, histological types were categorised into a high and low-risk group depending on anticipated survival. Survival analysis was performed utilising the Kaplan-Meier method on SPSS software version 24.0., Results: Of the 569 patients with renal tumors, 109 (19%) patients with primary (n = 97) or recurrent (n = 12) non-Wilms renal tumors were included. Histological high-risk group included clear cell sarcoma (CCSK) (39.4%), renal cell carcinoma (RCC) (19.3%), malignant rhabdoid tumor (MRTK) (12.8%), Ewing's sarcoma (rES) (15.6%), synovial sarcoma (2%), and undifferentiated sarcoma (2%). The low-risk group comprised of congenital mesoblastic nephroma (CMN) (4.6%), cystic partially differentiated nephroblastoma (2%), and other rare tumors (3%). Diagnostic error occurred in 2 patients in the high-risk group. All low-risk tumours were treated with surgery alone and most (97%) high-risk tumors were operated either upfront (61.5%) or after preoperative chemotherapy (38.4%). Adjuvant therapy based on histology was offered to 70%. The recurrent tumors received various salvage treatments including chemotherapy; radiotherapy; surgery and immunotherapy, however, only 2 patients could be salvaged. The 3-year overall survival for the entire cohort with primary tumors was 59%, and the survival rates were 76.7%, 77.9%, 0.0%, and 52% for CCSK, RCC, MRTK, and rES (summary figure). Low-risk tumors had 100% survival while the recurrent tumors had a median survival of 10.5 months., Conclusions: Non-Wilms renal tumors constitute a heterogeneous group of tumors, accounting for less than 20% of all renal tumors. Low-risk tumors are associated with excellent outcomes following surgery alone while the high-risk tumours have a variable outcome. MRTK and recurrent non-Wilms tumour have the worst survival. Favourable outcomes for CCSK and RCC and worst outcomes for MRTK were observed in this study. Renal ES have higher incidence of treatment failure and unsatisfactory outcomes. Recurrent non-Wilms tumours have an extremely poor outcome and more alternative or innovative approaches are needed for their treatment., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Wilms' tumour (WT) is the most common childhood renal tumour. Tumour-associated macrophages (TAMs) are a critical component of tumour microenvironments and contain two main subtypes, classically (M1) or alternatively (M2) activated macrophages. Evidence has revealed TAMs in predicting poor prognosis in some malignant tumours. However, the role of TAMs in WT is still unclear, and the relationship of different types of TAMs with prognosis has not been elucidated., Objective: The aim of the study was to explore the presence of two types of TAMs in WT and analyse the relationship of TAMs with prognosis., Study Design: Overall, 61 paediatric patients with WT underwent nephrectomy before any chemotherapy from April 2006 to March 2014. The tumour tissues were analysed by Western blot, immunohistochemistry, and immunofluorescence to explore the distribution of M1 and M2 macrophages in different stages. Kaplan-Meier analysis with regard to the relationship between the presence of TAMs and follow-up information was performed., Results: In the 61 patients (44 males and 17 females), there was a median age of 19 months (IQR 13-35.5); 47 patients are still alive, 11 died, 3 were lost to follow-up. According to the National Wilms Tumor Study (NWTS)-5 guidelines, the distribution of tumour stages was as follows: stage I, 27 patients; stage II, 18 patients; and stage III, 16 patients. The Western blot analysis showed that the density of M1 and M2 macrophages in tumour tissues were significantly greater than that in adjacent normal tissues. Immunohistochemistry showed the proportion of patients with positive M1-type macrophages across different stages: stage I, 66.7% (18/27); stage II, 44.4% (8/18); and stage III, 25% (4/16) (p = 0.027). The proportion of patients with positive M2-type macrophages across different stages: stage I, 25.9% (7/27); stage II, 55.6% (10/18); and stage III, 81.3% (13/16) (p = 0.002). Kaplan-Meier analysis suggested that patients with high densities of M2-type macrophages had shorter overall survival time than those with low densities (log-rank test, p = 0.011)., Discussion: TAMs play a pivotal comments in the tumour microenvironment and tumorigenesis. With the progression of clinical stage, M2 macrophage densities increased greatly, and M1 macrophage density decreased. M2 macrophages represent a poor prognosis and can be utilized as a new indicator in pathological examination., Conclusion: There is a high density of TAMs in WT, and M2-type macrophage density increases with tumour progression and implies a poor prognosis., Competing Interests: Conflicts of interest The authors declare that there are no conflicts of interest related to this article., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Given improvements in multimodality therapy, survival among children with Wilms tumor (WT) exceeds 90%. However, 15% of children with favorable histology and 50% of children with anaplastic WT experience recurrence or progression. Of patients with advanced disease, only 50% survive to adulthood. In adult malignancies (including renal tumors), patient survival has improved with the advent of immunotherapy. However, little is known about the immune microenvironment of WT, making the potential role of immunotherapy unclear., Objective: The objective of the study is to perform an exploratory, descriptive analysis of the immune milieu in WT., Study Design: Between 2016 and 2017, all pediatric patients with WT, some of whom received neoadjuvant chemotherapy, underwent ex vivo wedge biopsy at the time of nephrectomy. The fresh tumor tissue and peripheral blood samples were analyzed for infiltrating immune infiltrate and effector cells using flow cytometry. Immunohistochemistry was performed for CD4, CD8, and PD-L1 expression. Matched blood samples were obtained for each patient, and circulating immune cells were analyzed by flow cytometry., Results: A total of six patients were enrolled. One patient with neuroblastoma was excluded. The remaining five patients included the following: two with unilateral WT (resected before chemotherapy), two with bilateral WT (resected after neoadjuvant chemotherapy), and one with Denys-Drash syndrome, end-stage renal disease, and history of WT in the contralateral kidney. Immune analysis showed that WT were infiltrated by immune cells regardless of chemotherapy status. CD8 and CD4 T cells were present in the tumor tissue and exhibited an activated phenotype. Elevated levels of natural killer (NK) cells were observed in the tumors (Figure). Immune checkpoint PD-L1 was also found expressed in one of the tumors stained., Discussion: In this pilot study, it was found that WTs were infiltrated by immune cells (CD45+) both before and after chemotherapy. Elevated levels of NK cells infiltrating the tumor specimens, which were quantitatively increased compared with levels of NK cells circulating in the blood, were noted. T cells, particularly CD4+ and CD8+ T cells, were present in tumor specimens. Tumor-infiltrating CD4 and CD8 T cells displayed an activated phenotype as defined by increased expression of human leukocyte antigen-DR isotype (HLA-DR), programmed cell death protein 1 (PD1), and CD57. Together, these findings suggest that WT microenvironment is immune engaged and may be susceptible to immunotherapy similar to other malignancies., Conclusions: These pilot data suggest an immune-engaged tumor microenvironment is present within WT. This implies that WT may be susceptible to immunotherapy similar to adult renal tumors and other adult malignancies. Follow-up studies are currently underway., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Wilms' tumour is the most frequent renal tumour in children. Multi-modal treatment includes chemotherapy and surgery, with or without radiotherapy. The survival is excellent, with rates exceeding 90%. A review is presented on our experience over the last 15 years of treating Wilms' tumour in Hospital Niño Jesús, Madrid., Patients and Methods: A retrospective study was conducted on 40 consecutive paediatric patients diagnosed with nephroblastoma between 2002 and 2016 in the Hospital Niño Jesús in Madrid. The clinical characteristics, diagnostic methods, treatment, and follow-up were analysed., Results: Of the 40 patients, 23 were boys, with a median age at diagnosis of 2.5 years (range, 4 months-15 years). Three patients underwent initial nephrectomy, three received a fine needle aspiration biopsy, followed by chemotherapy, and 34 patients started pre-operative chemotherapy directly. The median follow-up of the patients was 6.75 years (range, 10 months - 13.92 years). Two patients died from disease progression. There were no treatment-related deaths. Overall survival and event-free survival at 5 years was 94.6±3.7% and 89.4±5%, respectively., Conclusion: Wilms' tumour treatment is a success of modern medicine, currently achieving a survival rate of 95% in our series., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

'High risk' renal tumors of childhood generally includes anaplastic Wilms tumor, rhabdoid tumor, and metastatic renal sarcomas and carcinomas. In this review, the epidemiology, biology, treatment and prognosis of anaplastic Wilms tumor and rhabdoid tumor are presented. Future directions related to management of such cancers are discussed, with insights provided into possible clinical trials in development that consider integration of novel targeted therapies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Wilms tumor is the most common primary renal malignancy occurring in childhood. Significant improvement has been made in the treatment of children with Wilms tumor. However, the treatment of patients with non-Wilms renal tumors remains challenging., Methods: Between 1991 and 2010, 70 children with renal tumors were diagnosed at a single institution. Fifty-four patients were histologically confirmed and divided into three groups, including 42 Wilms tumors, seven clear cell sarcomas of kidney, and five malignant rhabdoid tumors. Most patients underwent unilateral nephrectomy and lymph node sampling followed by adjuvant chemotherapy. Twenty-one of these patients subsequently received radiotherapy., Results: During follow-up, 12 patients died of progressive disease and one died of operative mortality. One patient with unilateral pleural metastases subsequently underwent hematopoietic stem cell transplantation. The median survival time of all patients was 88 months. Children under 2 years of age at diagnosis with Wilms tumor or clear cell sarcoma of kidney had an excellent survival rate of 100% compared to the 0% survival rate of MRT., Conclusion: Younger age at diagnosis bore a better prognosis than did older age, whereas a diagnosis of malignant rhabdoid tumor portended a worse prognosis. Younger patients and appropriate treatment may have contributed to the improved prognosis of clear cell sarcoma of kidney., (Copyright © 2013. Published by Elsevier B.V.)

In the past decades a great progress in cancer research has been made although medical treatment is still widely based on empirically established protocols which have many limitations. Computational models address such limitations by providing insight into the complex biological mechanisms of tumor progression. A set of clinically-oriented, multiscale models of solid tumor dynamics has been developed by the In Silico Oncology Group (ISOG), Institute of Communication and Computer Systems (ICCS)-National Technical University of Athens (NTUA) to study cancer growth and response to treatment. Within this context using certain representative parameter values, tumor growth and response have been modeled under a cancer preoperative chemotherapy protocol in the framework of the SIOP 2001/GPOH clinical trial. A thorough cross-method sensitivity analysis of the model has been performed. Based on the sensitivity analysis results, a reasonable adaptation of the values of the model parameters to a real clinical case of bilateral nephroblastomatosis has been achieved. The analysis presented supports the potential of the model for the study and eventually the future design of personalized treatment schemes and/or schedules using the data obtained from in vitro experiments and clinical studies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The randomised findings of the UKW3 trial were that preoperative chemotherapy was associated with a more advantageous stage distribution and reduction in therapy burden versus immediate nephrectomy without compromising outcome in localised Wilms' tumour (WT). We analysed outcome in all WT registered in UKW3., Patients and Methods: Seven hundred and eighteen WT cases (7% anaplastic) were registered in UKW3. We assigned a treatment stage and conducted survival analysis., Results: Five-year event-free survival (EFS) and overall survival (OS) were 77.2% [95% confidence interval (CI) 73.9-80.2] and 87.5% (95% CI 84.8-89.7) after median follow-up of 9.5 years and 10.0 years, respectively. Five-year OS in localised non-anaplastic cases was 92.9% (95% CI 90.2-94.9). Anaplasia was associated with adverse outcome compared with non-anaplastic cases: 5-year EFS of 42.0% (95% CI 28.3-55.1) versus 79.8% (95% CI 76.5-82.7) and 5-year OS of 60% (95% CI 45.1-72.0) versus 89.6% (95% CI 87.0-91.7), respectively. Outcomes were similar for non-anaplastic stage I or II but significantly poorer in stage III cases than stage I. Five-year OS after relapse was 54.1% (95% CI 44.5-62.8). Forty-seven percent of non-anaplastic WT received anthracycline; 27% were treated with radiotherapy first line., Conclusion: These outcomes provide a baseline for future comparisons of WT treatment approach, burden and patient outcome.

Breast cancer at age 21 is rare, even in individuals who have a genetic predisposition. These early diagnoses are usually the result of a hereditary cancer syndrome. Other contributing factors, such as chemotherapy and radiation for previous malignancies, can also increase the risk of secondary malignancies, including breast cancer. Here we present one of the youngest cases of breast cancer reported in the literature: a 21-year-old Wilms' tumor survivor (diagnosed at age 6), who was found to have a familial BRCA1 mutation and was diagnosed with ductal carcinoma in situ at age 21., (Copyright © 2011. Published by Elsevier Inc.)

We report on a rare case of botryoid Wilms tumor extending into the duodenum. This uncommon macroscopic form of nephroblastoma consists entirely of a polypoid renal intrapelvic mass. The main differential diagnosis of this unusual tumor is botryoid rhabdomyosarcoma. A 14-month-old boy presented with a painful abdominal mass. Radiology revealed a large heterogeneous mass in the renal calyx, protruding into the ureter. A right radical nephroureterectomy was carried out. The tumor was found to extend into the 2nd portion of the duodenum. The pathologic diagnosis was mixed type nephroblastoma, SIOP 2001 stage III. The patient was given a course of postoperative chemotherapy. No local recurrence or metastatic spread has been detected after 2 years. Only few such cases have been previously reported, some of them extending into the bladder. To our knowledge, botryoid nephroblastoma has not previously been described as extending into the digestive system., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Introduction: Primary lung adenocarcinoma is extremely rare in the pediatric age group. There have been anecdotal reports of lesions that are histologically indistinguishable from adult-type pulmonary adenocarcinoma in young patients after treatment for nonpulmonary cancers. Herein, we present clinical, histopathologic, and molecular data on eight such cases., Methods: Histopathologic evaluation of the tumors was performed according to the World Health Organization classification. Molecular studies for EGFR and KRAS mutations were performed on six patients with sufficient material., Results: All eight patients were never smokers, four males and four females. Median age at nonpulmonary cancer diagnosis was 14 years (range, 3-23 years). Pulmonary adenocarcinomas were diagnosed at a median age of 15 years (range, 10-24 years); tumors were 0.1 to 2.0 cm in size and in some cases coexisted with metastases from the original cancer. Retrospective review showed that in at least three patients, the nodules were radiographically present before chemotherapy. Of six patients whose tumors were tested for common EGFR and KRAS mutations, two were positive for the former and one for the latter. At a median follow-up of 11 months (range, 2-29 months), six patients remained well without lung nodules and two had additional small, peripheral lung nodules that have not been biopsied., Conclusions: Pulmonary lesions found in young patients with pediatric cancers can be histologically indistinguishable from lung adenocarcinoma seen in adults, may display typical adenocarcinoma-associated mutations of EGFR and KRAS, and may precede the administration of cytotoxic chemotherapy.

Neonatal renal tumours are rare, with only 7% of all neonatal tumours arising from the kidney. Presentation is usually as a flank mass or as a coincidental finding on either antenatal or postnatal ultrasound. Mesoblastic nephroma is the most common tumour to be found at this age, but Wilms' tumour and other malignant and benign tumours occur. Cross sectional imaging is useful to delineate the extent of the disease. Given the low malignant potential of these tumours, treatment is by radical nephroureterctomy, except in cases with bilateral disease or syndromic patients with a high incidence of metachronous tumours. Chemotherapy is rarely indicated. Survival is generally excellent for all tumour types in this age group, the exception being malignant rhabdoid tumour of the kidney which may have metastases at presentation., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Rhabdoid tumours are rare aggressive tumours of infancy. The definition classically relies on a characteristic morphology and the inactivation of the hSNF5/INI1 tumour suppressor gene. This entity includes central nervous system tumours (ATRT), renal tumours (RTK) and soft-part tumours. Their rarity and morphological pleomorphism make the diagnosis often challenging. However, the recently introduced immunohistochemistry with anti-INI1 (anti-SMARCB1) antibody is a very useful diagnostic tool. Deletions at the 22q11.2 locus and mutations in hSNF5/INI1 sequence must be investigated in order to confirm the diagnosis and to give insights on a presumable germline mutation. Indeed, a predisposition may be found in up to 30% of cases. The treatment is based on aggressive chemotherapy, surgery and irradiation. The prognosis remains poor and the survival rate is below 30%, whatever the anatomic location. Understanding the role of hSNF5/INI1 within the SWI-SNF complex for the epigenetic regulation of transcription might drive the future targeted therapies.

Purpose: Wilms' tumor is the most common renal tumor in children. Outcomes have improved dramatically over the past few decades, but important treatment questions remain. These include the role of molecular biologic markers in stratifying patients for therapy or targeting tumors for treatment. We present a summary of these advances and outline the current treatment of Wilm's tumor., Materials and Methods: The medical literature and results of all cooperative group studies reporting treatment of children with Wilms' tumor were reviewed., Results: Overall survival exceeds 90% for most patients with nephroblastoma. However, outcomes for patients with rhabdoid tumors and diffuse anaplasia remain poor. The role of renal sparing surgery in patients with bilateral tumors is clear, but for children with unilateral tumors it continues to be defined., Conclusions: Current protocols conducted by pediatric oncology groups are beginning to incorporate biologic features to stratify patients for therapy. Treatment strategies continue to focus on limiting late effects of treatment while maintaining an excellent survival. New therapies are needed to treat the high-risk patients who continue to have high relapse and mortality rates.

The development of cancer vaccines directed against myeloid leukaemias has been a research area of intense interest in the past decade. Both human studies in vitro and mouse models in vivo have demonstrated that leukaemia-associated antigens (LAAs), such as the fusion protein BCR-ABL, Wilms' tumour protein and proteinase 3, may serve as effective targets for cellular immunotherapy. Peptide-based vaccines are able to induce cytotoxic T-lymphocyte responses that kill leukaemia cells. Based on these results, pilot clinical trials have been initiated in chronic and acute myeloid leukaemia and other haematological malignancies, which include vaccination of patients with synthetic peptides derived from these LAAs. Results from these trials show that peptide vaccines are able to induce immune responses that are sometimes associated with clinical benefit. These early clinical results are promising and provide valuable information for future improvement of the vaccines. This chapter will focus mainly on discussing the preclinical studies of peptide vaccines in human systems, the results from clinical trials and the future prospects for vaccine therapy for myeloid leukaemia.

Aims: To review the management of Wilms' tumour., Methods: A search of the literature was performed using the PubMed database (1966 to May 2006) with the search terms 'Wilms' and either 'tumour/tumor' or 'cancer' or 'carcinoma'. This was augmented by manual searches of publications., Findings: The success of clinical trials in Wilms' tumour patients over the past 30 years has led to an overall survival of 85% and the introduction of less aggressive chemotherapeutic regimes for patients. Large randomised controlled trials have been published on the management of Wilms' tumour by various collaborative groups, including the National Wilms' Tumour Study Group (NWTSG) in North America and the Société Internationale d'Oncologie Pédiatrique (SIOP) plus the United Kingdom Children's Cancer Study Group (UKCCSG) in Europe., Conclusions: Controversy exists as to the best approach to the management of these children with regard to neoadjuvant chemotherapy. Challenges remain in the identification of histological and molecular risk factors for the stratification of treatment intensity.

Background: Advances in paediatric oncology has tremendously improved the outcome in children with nephroblastoma. In most developing countries, however, the survival rate is still very low., Objective: To study the outcome and the impediments to the management of nephroblastoma in Southeast Nigeria., Methods: Analysis of 42 children managed for nephroblastoma over a 10-year period (January 1995-December 2004) at the University of Nigeria Teaching Hospital, Enugu, Nigeria is made. Diagnosis was based on clinical, radiologic and histologic evaluation., Results: The peak age incidence was 2-5 years with a male:female ratio of 1.1:1. Abdominal mass was the main presentation in all the children. Treatment consisted of nephroureterectomy followed by adjuvant chemotherapy with Vincristine, Actinomycin D and Cyclophosphamide. Adriamycin was added for metastatic disease. Twenty-two children (52.3%) had stage III disease, 13 (31.0%) had stage IV, while the remaining seven (16.7%) children had stage II. Stage I disease was not encountered. Seven children had inoperable tumor requiring pre-operative chemotherapy. While 25 children were available for evaluation, 17 were lost to follow up. Four children died of complications of treatment, while 11 relapsed with poor outcome. With a mean follow up of 21 months, the 5-year survival rate is 40%., Conclusion: Morbidity and mortality with nephroblastoma is high in our environment. Late presentation, poverty, ignorance and poor compliance to treatment constitute a great challenge to the paediatric oncologist in a developing country. Solutions may lie in improving health funding and health information in the health care delivery system. Free health care for children with malignancy is advocated. Collaboration with institutions in the privileged parts of the world may help.

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives, the SOR SAVOIR PATIENT program. The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information developed in this program is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres,the National League against Cancer, The National Cancer Institute, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals, the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The handbook SOR SAVOIR PATIENT Understanding nephroblastoma is an adapted version of various scientific publications and international clinical practice guidelines, validated by oncology experts and by the Nephroblastoma Committee of the French Society against Cancers and Leukaemias in children and adolescents (SFCE). It was elaborated with the active participation of parents and other family members. It is meant to provide a basis for the explanation of the disease, to help parents asking questions, and to facilitate discussions with the healthcare team. It is available from the FNCLCC (101, rue de Tolbiac, 75013 PARIS, Tel. (0033)1 76 64 78 00, www.fnclcc.fr). This document was validated at the end of 2005 and published in May 2006. SOR SAVOIR PATIENT guides are systematically updated when new research becomes available. Information leaflets, extracted from the handbook SOR SAVOIR PATIENT Understanding nephroblastoma and published in this edition of the Cancer et Radiothérapie, describe the physiopathology of nephroblastoma, as well as treatments and follow-up. The guide allows parents and relatives to better understand the disease and the treatments proposed. It also offers health professionals a synthetic evidence-based patient information source which facilitates discussions with the patient.

Unlabelled: Thymic hyperplasia in response to stress is a well known phenomenon. Thymic hyperplasia has also been described after chemotherapeutic treatment for malignancies in children., Case Report: A three-year-old girl was followed up from the age of 18 months for a left kidney nephroblastoma treated by combination of chemotherapy (vincristin, actinomycin and adriamycin) and surgery. Assessment at the end of treatment was normal. Four months after the end of treatment, pulmonary radiography showed mediastinal enlargement, which was shown to originate in the thymus at thoracic CT scan. A recurrence of the disease was suspected. Biopsy showed thymic hyperplasia without evidence of tumor cells. Mediastinal enlargement then disappeared spontaneously 2 months later., Conclusion: Thymic hyperplasia occurring during remission of a cancer treated by chemotherapy is a diagnostic dilemma as it suggests mediastinal reccurence of the disease. Needle aspiration cytology is an appropriate investigation in thymic hyperplasia. No steroid therapy should be used before histologic diagnosis of thymic hyperplasia.

Isolated involvement of the left heart chambers by metastases of malignant tumors is extremely rare. We report a case of an 8-year-old child, with a left atrial metastasis of a Wilms' tumor detected in a control nuclear magnetic resonance 1 year after left inferior lobectomy for metastatic extension of the kidney tumor, which was diagnosed 4 years earlier. The metastasis was excised en bloc with a disc of the posterior left atrial wall.

Background: Recent Wilms' tumor (WT) trials and studies have tried to determine the minimal therapy needed for cure. The goal was survival without morbidity., Patients and Methods: From January 1989 to March 1994 the German Society of Pediatric Oncology and Hematology registered 440 patients (median age 2.9 years; 231 male, 209 female) with WTs (preoperative chemotherapy 362) for therapy according to the International Society of Pediatric Oncology Trial and Study 9. Therapy for relapse depended on site of relapse and therapy already received. Follow-up included inquiries for morbidity. Prognostic factors for relapse and death were evaluated., Results: Five-year survival of WTs was 89.5%; 98.2% (385 of 392) of survivors had a follow-up of 5 years (range 0.8-12.6; median 8). In non-anaplastic WTs, young age (<2 years) was of significance (P = 0.026) for a better survival. Non-anaplastic WTs (407 patients) had a 5-year survival of 92.3%, versus 48.5% in anaplastic WTs (33 patients), and a 5-year relapse-free survival of 87.6% versus 42.4%. Survival after relapse was significantly worse for anaplastic than for non-anaplastic WTs (residual 3-year survival 11.8% versus 54.3%; P <0.0001). In preoperatively treated WTs, anaplasia was a strong prognostic factor for death [relative risk (RR) 4.7], followed by poor response to preoperative therapy (RR 3.6), stage IV (RR 3.2) and abdominal stage III (RR 2.2). Low abdominal stages (

Since its initial description by Max Wilms over a century ago, nephroblastoma has benefited from considerable improvements both in terms of basic knowledge about it and management of it. Today, the majority of these very young patients can expect a long-term survival in excess of 90% at the price of a light therapy that combines surgical resection, chemotherapy based on ill-toxic agents, and in selected cases, radiotherapy of remarkably low toxicity. The contribution of large international studies will be emphasized here.

Background: Nephrogenic rests generally constitute precursor lesions of Wilms' tumor. We report a case of right nephroblastomatosis with dysmorphic features., Case Report: An enlargement of the right kidney was incidentally discovered in a 1-year-old girl with dysmorphic features but normal psychomotor development. Combined ultrasonography and computerized tomography (CT) scan showed right cortical nephroblastomatosis. Chemotherapy using actinomycin D and vincristin was successful; however, an hyperechogenic nodule was subsequently found, necessitating a right nephrectomy., Conclusion: The relationship between nephroblastomatosis and Wilms' tumor is discussed. This case report reminds us of the importance of a long-term follow-up including echography and CT scan in cases of nephroblastomatosis.

Background: Nephroblastoma' the most common renal tumor in children between 1 and 5 years, occurs rarely in the oldest child., Case Report: A 16-year-old teenager suffered from acute pyelonephritis caused by Klebsiella pneumoniae. Renal ultrasonography showed a left subcapsular hematoma; the CT scan confirmed the finding and also showed renal scarring. However, a second CT scan showed pulmonary nodules suggestive of metastasis, a diagnosis that was confirmed by needle biopsy of pulmonary lesions. Recovery was obtained after chemotherapy and nephrectomy with a 3-year-follow-up., Conclusion: This nephroblastoma was particular because its development in an adolescent, its association with acute pyelonephritis and subcapsular hemorrhage.

Background: Wilms tumor is associated in 7 to 10% of patients with congenital abnormalities. Among those, aniridia is the most constant feature of the WAGR syndrome that includes, in one third of cases. Wilms tumor. We report two cases of aniridia associated with fetal rhabdomyomatous nephroblastoma., Case Reports: Case 1. A one-year old girl with congenital aniridia was admitted for macroscopic hematuria. Abnormal ultrasonography and tomodensitometry revealed a large, bilateral, kidney tumor. The patient was given actinomycin and vincristine, without efficacy. Bilateral tumorectomy was performed 6 months later and the histological study showed a fetal rhabdomyomatous nephroblastoma. This patient is in remission at the age of 5. Case 2. A boy, also with congenital aniridia, presented with macroscopic hematuria at the age of 2 years revealing a nephroblastoma located on his right kidney. Preoperative chemotherapy remained uneffective and the nephrectomy performed 1 month later permitted the diagnosis of fetal rhabdomyomatous nephroblastoma. The patient is well 4 years later., Conclusion: Both cases of fetal rhabdomyomatous nephroblastoma, a histological variant of Wilms tumor, seem to be the first reported in the WAGR syndrome.

The favourable results from the treatment of Wilms' tumour are an example of the success of multimodal therapy in paediatric oncology. The epidemiology, methods of diagnosis, benefits of pre-operative chemotherapy, basic principles of surgery and post-operative treatment modalities are presented. The approach to the management of Wilms' tumour considered in this paper is mainly that of the International Society of Paediatric Oncology.

A recent Consensus Conference in Lyon reviewed the role of high-dose therapy with stem cell rescue in a variety of malignancies including childhood tumours. The conclusion was that with the exception of metastatic neuroblastoma there is still no proven role for this treatment strategy. It is more than 10 years since this approach was used in neuroblastoma and it has subsequently been applied to most of the common childhood solid tumours. Although a single randomised study has suggested that the progression-free survival is significantly prolonged with high-dose melphalan, the superiority of this over continued intensive conventional therapy is unclear. It seems likely that a selected subgroup of children with stage IV disease may benefit from megatherapy and the results of current randomised trials are awaited. In rhabdomyosarcoma, the duration of treatment may be shortened by dose escalation, but the impact on the outcome in very high-risk patients remains unproven. In Ewing's sarcoma, there has been difficulty defining high-risk patients, but recent studies suggest that megatherapy may have a role in patients with bone or bone marrow disease who have little chance of long-term survival with conventional chemotherapy approaches. In brain tumours, the results have been disappointing for gliomas, but there is currently enthusiasm about a possible role in the chemosensitive primitive neuroectodermal tumours. In this group of diseases which are inherently chemosensitive, the poor results from chemotherapy in the past have resulted from a failure to achieve appropriate drug levels at the tumour site and this may be potentially overcome by dose escalation. In Wilms' tumour, although the overall cure rate is very high, there appears to be a useful role for megatherapy in certain high-risk relapsed patients who have little chance of cure with conventional salvage therapy. There is an urgent need for international collaboration to design randomised studies which will as rapidly as possible address the issue of the role of these expensive and high morbidity procedures in childhood cancer.

We present the case of a boy who underwent orthotopic heart transplantation at the age of 14 years because of doxorubicin-induced cardiomyopathy 9 years after treatment of a Wilms tumor of the left kidney. Three years after heart transplantation the patient enjoys a normal daily life. Invasive studies show normal cardiac hemodynamic results and in spite of previous nephrectomy and long-term cyclosporine treatment, renal function is only slightly impaired. So far no secondary neoplasia has occurred under chronic immunosuppression.

The effectiveness of central parenteral nutrition (CPN) versus peripheral parenteral nutrition (PPN) plus enteral nutrition in reversing protein-energy malnutrition was evaluated in 19 children (nine CPN, 10 PPN) with advanced neuroblastoma or Wilms' tumor. Weekly dietary, anthropometric, and biochemical measurements were compared for 15 patients (eight CPN, seven PPN) who completed more than 25 days of nutrition support. The groups had similar mean energy and protein intakes (CPN: 95 +/- 5% of healthy children, 2.5 +/- 0.3 g/kg; PPN: 102 +/- 5% of healthy children, 2.9 +/- 0.3 g/kg). Increases in weight (p less than 0.001), subscapular skinfold thickness (p less than 0.001), albumin (p less than 0.05), and transferrin (p less than 0.05) for the first 28 days were significant and did not differ between groups. Fever, sepsis, elevated SGOT, and severe anemia occurred with both CPN and PPN. PPN resulted in subcutaneous infiltrations and more psychological trauma. PPN with enteral nutrition seems most appropriate for short term intravenous nutrition support or as a temporary substitute for CPN; CPN is preferred for long-term support.