Clinical characteristics and outcomes of children with WAGR syndrome and Wilms tumor and/or nephroblastomatosis: The 30-year SIOP-RTSG experience

BACKGROUND: WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare contiguous gene deletion syndrome with a 45% to 60% risk of developing Wilms tumor (WT). Currently, surveillance and treatment recommendations are based on limited evidence. METHODS: Clinical characteristics, treatments, and outcomes were analyzed for patients with WAGR and WT/nephroblastomatosis who were identified through International Society of Pediatric Oncology Renal Tumor Study Group (SIOP-RTSG) registries and the SIOP-RTSG network (1989-2019). Events were defined as relapse, metachronous tumors, or death. RESULTS: Forty-three patients were identified. The median age at WT/nephroblastomatosis diagnosis was 22 months (range, 6-44 months). The overall stage was available for 40 patients, including 15 (37.5%) with bilateral disease and none with metastatic disease. Histology was available for 42 patients; 6 nephroblastomatosis without further WT and 36 WT, including 19 stromal WT (52.8%), 12 mixed WT (33.3%), 1 regressive WT (2.8%) and 2 other/indeterminable WT (5.6%). Blastemal type WT occurred in 2 patients (5.6%) after prolonged treatment for nephroblastomatosis; anaplasia was not reported. Nephrogenic rests were present in 78.9%. Among patients with WT, the 5-year event-free survival rate was 84.3% (95% confidence interval, 72.4%-98.1%), and the overall survival rate was 91.2% (95% confidence interval, 82.1%-100%). Events (n = 6) did not include relapse, but contralateral tumor development (n = 3) occurred up to 7 years after the initial diagnosis, and 3 deaths were related to hepatotoxicity (n = 2) and obstructive ileus (n = 1). CONCLUSIONS: Patients with WAGR have a high rate of bilateral disease and no metastatic or anaplastic tumors. Although they can be treated according to existing WT protocols, intensive monitoring of toxicity and surveillance of the remaining kidney(s) are advised. LAY SUMMARY: WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare genetic condition with an increased risk of developing Wilms tumor. In this study, 43 patients with WAGR and Wilms tumor (or Wilms tumor precursor lesions/nephroblastomatosis) were identified through the international registry of the International Society of Pediatric Oncology Renal Tumor Study Group (SIOP-RTSG) and the SIOP-RTSG network. In many patients (37.5%), both kidneys were affected. Disease spread to other organs (metastases) did not occur. Overall, this study demonstrates that patients with WAGR syndrome and Wilms tumor can be treated according to existing protocols. However, intensive monitoring of treatment complications and surveillance of the remaining kidney(s) are advised

Characteristics and outcome of pediatric renal cell carcinoma patients registered in the International Society of Pediatric Oncology (SIOP) 93‐01, 2001 and UK‐IMPORT database: A report of the SIOP‐Renal Tumor Study Group

In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric Oncology‐Renal Tumor Study Group (SIOP‐RTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93‐01, 2001 and UK‐IMPORT databases, were included. Event‐free survival (EFS) and overall survival (OS) were analyzed using the Kaplan‐Meier method. Between 1993 and 2019, 122 pediatric patients with RCC were registered. Available detailed data (n = 111) revealed 56 localized, 30 regionally advanced, 25 metastatic and no bilateral cases. Histological classification according to World Health Organization 2004, including immunohistochemical and molecular testing for transcription factor E3 (TFE3) and/or EB (TFEB) translocation, was available for 65/122 patients. In this group, the most common histological subtypes were translocation type RCC (MiT‐RCC) (36/64, 56.3%), papillary type (19/64, 29.7%) and clear cell type (4/64, 6.3%). One histological subtype was not reported. In the remaining 57 patients, translocation testing could not be performed, or TFE‐cytogenetics and/or immunohistochemistry results were missing. In this group, the most common RCC histological subtypes were papillary type (21/47, 44.7%) and clear cell type (11/47, 23.4%). Ten histological subtypes were not reported. Estimated 5‐year (5y) EFS and 5y OS of the total group was 70.5% (95% CI = 61.7%‐80.6%) and 84.5% (95% CI = 77.5%‐92.2%), respectively. Estimated 5y OS for localized, regionally advanced, and metastatic disease was 96.8%, 92.3%, and 45.6%, respectively. In conclusion, the registered pediatric patients with RCC showed a reasonable outcome. Survival was substantially lower for patients with metastatic disease. This descriptive study stresses the importance of full, prospective registration including TFE‐testing

Australia's National Bowel Cancer Screening Program: does it work for Indigenous Australians?

<p>Abstract</p> <p>Background</p> <p>Despite a lower incidence of bowel cancer overall, Indigenous Australians are more likely to be diagnosed at an advanced stage when prognosis is poor. Bowel cancer screening is an effective means of reducing incidence and mortality from bowel cancer through early identification and prompt treatment. In 2006, Australia began rolling out a population-based National Bowel Cancer Screening Program (NBCSP) using the Faecal Occult Blood Test. Initial evaluation of the program revealed substantial disparities in bowel cancer screening uptake with Indigenous Australians significantly less likely to participate in screening than the non-Indigenous population.</p> <p>This paper critically reviews characteristics of the program which may contribute to the discrepancy in screening uptake, and includes an analysis of organisational, structural, and socio-cultural barriers that play a part in the poorer participation of Indigenous and other disadvantaged and minority groups.</p> <p>Methods</p> <p>A search was undertaken of peer-reviewed journal articles, government reports, and other grey literature using electronic databases and citation snowballing. Articles were critically evaluated for relevance to themes that addressed the research questions.</p> <p>Results</p> <p>The NBCSP is not reaching many Indigenous Australians in the target group, with factors contributing to sub-optimal participation including how participants are selected, the way the screening kit is distributed, the nature of the test and comprehensiveness of its contents, cultural perceptions of cancer and prevailing low levels of knowledge and awareness of bowel cancer and the importance of screening.</p> <p>Conclusions</p> <p>Our findings suggest that the population-based approach to implementing bowel cancer screening to the Australian population unintentionally excludes vulnerable minorities, particularly Indigenous and other culturally and linguistically diverse groups. This potentially contributes to exacerbating the already widening disparities in cancer outcomes that exist among Indigenous Australians. Modifications to the program are recommended to facilitate access and participation by Indigenous and other minority populations. Further research is also needed to understand the needs and social and cultural sensitivities of these groups around cancer screening and inform alternative approaches to bowel cancer screening.</p

Chemokine production by buccal epithelium as a distinctive feature of pediatric Crohn disease

Objectives: Inflammatory bowel diseases (IBD) represent an aberrant immune response by the mucosal immune system to luminal bacteria. Because the oral mucosa harbors the first epithelial cells that interact with microorganisms, we assessed the immunologic activity of buccal epithelium in children with IBD and adults with Crohn disease. Methods: Buccal epithelial cells were obtained from 17 children and 14 adults with Crohn disease, 18 children with ulcerative colitis, and 40 controls. Cells were cultured with and without microbial stimulation. Chemokine levels were determined in culture supernatants by cytometric bead array and enzyme-linked immunoabsorbent assay. CXCL-8 production was studied by immunohistochemical analysis of these cells. CXCL-8 production by lipopolysaccharide stimulated monocyte-derived dendritic cells from these patients was determined. Results: Compared with controls, pediatric ulcerative colitis patients, and adult Crohn disease patients, only in children with Crohn disease did buccal epithelial cells exhibit enhanced production of CXCL-8, CXCL-9, and CXCL-10. In vitro stimulation with lipopolysaccharide or zymosan resulted in a further increase of chemokine levels only in cells from pediatric Crohn disease patients. CXCL-8 production by stimulated monocyte-derived dendritic cells from children with Crohn disease was equal to that of children with ulcerative colitis. Conclusions: Buccal epithelium of children with Crohn disease is immunologically active, even in the absence of oral lesions. The enhanced chemokine production is associated with pediatric Crohn disease and appears restricted to cells derived from the epithelial barrier. Assessment of chemokine production by buccal epithelial cells may become a new, rapid, noninvasive test for screening and classification of IBD in children. (C) 2006 Lippincott Williams & Wilkins