219 How to manage the patient who presents with stage IV colorectal cancer. The role of the colorectal surgeon

Abstract

Wilms' tumor, or nephroblastoma, is the most common malignant renal tumor of childhood. It occurs with an annual incidence of 7 cases per million children aged less than 15 years.9 Approximately 450 new cases are diagnosed each year in North America. Although at the beginning of this century, most children with Wilms' tumor died of the disease, survival now exceeds 80%.26 This tremendous success story in childhood cancer was facilitated initially by individuals. Subsequent advances were achieved by institutions and cooperative groups. In the past 3 decades, the National Wilms' Tumor Study Group (NWTSG) and the International Society of Paediatric Oncology (SIOP) have contributed to improving the clinical management of children affected by Wilms' tumor. The NWTSG has studied most patients with Wilms' tumor in North America in randomized trials since 1969 and has collected data on more than 6000 patients. Based on a strategy of immediate nephrectomy, the NWTSG recommends early surgical resection of the tumor and affected kidney.35 Subsequently, depending on the histology of the tumor and the clinicopathologic stage, patients should receive chemotherapy. Patients with advanced disease or specific adverse prognostic features should receive additional radiotherapy. In contrast, the SIOP approach recommends preoperative chemotherapy for all tumors, with postoperative treatment for localized tumors dictated according to the stage assigned at the time of surgery.33Although it is a rare disease, Wilms' tumor is one of the childhood cancers that have provided significant information regarding the genetic events leading to the development of cancer in general. Wilms' tumors do not display as much genetic instability69 as adult cancers; hence, the majority of genetic alterations observed are likely to have a role in their development. The systematic study of Wilms' tumor occurring in association with congenital abnormalities has increased understanding of the pathogenesis of this childhood cancer. For example, WT1, the first Wilms' tumor suppressor gene at chromosome 11p13, was identified as a direct result of the study of children with Wilms' tumor who also had aniridia, mental retardation, and genitourinary anomalies. Karyotypic analysis of these children revealed a deletion within the short arm of one copy of chromosome 11.87 Study of the deleted region at band p13 led to the cloning of WT1 in 1990.11, 17, 32 This gene encodes a transcription factor critical to normal kidney and gonadal development.59 Similarly, the study of patients with Wilms' tumor and Beckwith-Wiedemann syndrome, another congenital Wilms' tumor predisposition syndrome, implicated the existence of a second Wilms' tumor suppressor gene, designated WT2. The existence of additional genetic loci involved in the development of Wilms' tumor is suggested by linkage analyses in large pedigrees with familial transmission of susceptibility to Wilms' tumor.70, 84 Loci at 16q,20, 38, 69 1p,38 7p,72, 88, 98 and 17p5, 64 have also been evoked in the biology of Wilms' tumor, although these loci do not predispose to Wilms' tumor but are associated with phenotype or outcome.This article reviews the most important known genetic loci involved in the biology of Wilms' tumor.