Controversies and advances in the management of Wilms' tumour

Pritchard‐Jones, Kathy

doi:10.1136/adc.87.3.241

Cited by 77 publications

(58 citation statements)

References 30 publications

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“…The main argument in favor of preoperative chemotherapy in WT is the higher incidence of tumor ruptures during surgery in cases that have not been pretreated, implicating upstaging of the tumor and radiation therapy. In the UK Children's Cancer Study Group UKW 3 study, which randomized the use of preoperative chemotherapy, outcomes did not differ between the 2 groups, but the group treated with immediate surgery showed considerably more tumor ruptures, which was comparable with the rupture incidence found by the National Wilms' Tumor Study Group [14][15][16] . Moreover, presurgery chemotherapy for WT enables the identification of high-risk patients (i.e.…”

Section: Therapymentioning

confidence: 92%

Cystic Nephroma, Cystic Partially Differentiated Nephroblastoma and Cystic Wilms’ Tumor in Children: A Spectrum with Therapeutic Dilemmas

Hoek¹,

Krijger²,

Ven

et al. 2009

Urol Int

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Background: Cystic renal tumors are a diagnostic and therapeutic challenge. Cystic nephroma (CN), cystic partially differentiated nephroblastoma (CPDN) and cystic Wilms’ tumor (CWT) are a spectrum with CN at the benign end, CWT at the malignant end and CPDN in the intermediate position. CN and stage 1 CPDN are often treated with surgery alone. International Society of Pediatric Oncology (SIOP) protocols for Wilms’ tumor (WT) advocate preoperative chemotherapy, which may be unnecessary and potentially harmful in CN and in stage 1 CPDN. There are difficulties in differentiating the three types using imaging techniques. Therefore, controversies exist regarding the optimal treatment. Methods: We describe 6 children, who each had a postoperative diagnosis of CN, CPDN or CWT, and we retrospectively evaluate the treatment strategies. Results: The three types cannot be differentiated using imaging techniques, although the presence of solid components in the tumor is indicative of WT. Conclusions: Surgery as first-line therapy should be seriously considered in children who have a cystic renal tumor, but further collaborative studies are needed since the distinction line between CPDN and CWT is not always clear.

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Section: Therapymentioning

confidence: 92%

Cystic Nephroma, Cystic Partially Differentiated Nephroblastoma and Cystic Wilms’ Tumor in Children: A Spectrum with Therapeutic Dilemmas

Hoek¹,

Krijger²,

Ven

et al. 2009

Urol Int

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“…Nevertheless, a poor prognostic subgroup of nephroblastomas remains. Diffuse anaplasia, persistent blastema after chemotherapy, allelic loss at 1p or 16q, TP53 mutations and advanced tumour stage have been identified as adverse prognostic factors [3,10,11,31,32]. Therefore, development of novel therapeutic strategies is mandatory.…”

Section: Introductionmentioning

confidence: 99%

KIT, PDGFRα and EGFR analysis in nephroblastoma

et al. 2008

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Nephroblastoma prognosis has dramatically improved, but an unfavourable prognostic subgroup warrants development of novel therapeutic strategies. Selective KIT, PDGFRalpha and epidermal growth factor receptor (EGFR) tyrosine kinase inhibition evolved as powerful targeted therapy for gastrointestinal stromal tumours and non-small-cell lung cancer. To investigate a potential role for tyrosine kinase inhibition, we analyzed 209 nephroblastomas for immunohistochemical KIT and EGFR expression, 63 nephroblastomas for mutations in KIT exons 9, 11, 13, EGFR exons 18, 19, 20 and 21, and all 209 nephroblastomas for PDGFRalpha exons 12, 14 and 18. Twenty-two tumours (10.5%) expressed KIT, 31 (14.8%) EGFR, and 10 (4.8%) both KIT and EGFR, respectively. KIT expression was relatively more common among high-risk tumours (6/27; 22.3%) compared to low-/intermediate-risk tumours (26/181; 14.4%). Nine patients deceased, four of which had high-risk tumours with KIT expression in two of four and EGFR expression in one of four. There were no KIT, PDGFRalpha or EGFR mutations. Our results suggest no significant contribution of KIT, EGFR or PDGFRalpha mutations to nephroblastoma pathogenesis. Despite a trend towards association of immunohistochemical KIT and EGFR expression with poor outcome in high-risk nephroblastomas, statistical analysis did not yield significant correlations in this subgroup. Therefore, it remains open if KIT, PDGFRalpha or EGFR tyrosine kinase inhibition constitute a therapeutic target in nephroblastoma in the absence of KIT, PDGFRalpha or EGFR mutations.

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“…[17][18][19] Therefore, novel treatment options for both RCC and nephroblastoma are the subject of ongoing research. 14,15,20 Our aim in the present study was to investigate NPY receptor expression in these 2 most common adult and childhood kidney cancers as well as in the nonneoplastic kidney using NPY receptor autoradiography.…”

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confidence: 99%

Neuropeptide Y receptors in renal cell carcinomas and nephroblastomas

Körner

Waser

Reubi

2005

Intl Journal of Cancer

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Numerous peptide receptors are overexpressed in human cancer, permitting in vivo tumor targeting. Among such receptors, those for the neurotransmitter neuropeptide Y (NPY) are overexpressed in various tumors. Since NPY can play a role in the kidney, NPY receptor expression and/or endogenous production of peptides of the NPY family (NPY, PYY, PP) were evaluated in 40 renal cell carcinomas (RCCs) and 18 nephroblastomas. NPY receptor protein expression was investigated by in vitro autoradiography using 125 I-labeled PYY in competition with NPY receptor subtype-selective analogs. NPY, PYY and PP production was assessed immunohistochemically. Fifty-six percent of RCCs expressed the Y1 receptor subtype in moderate density, and 80% of nephroblastomas expressed Y1 and Y2 subtypes in moderate to high density. Y1 was also highly expressed in intratumoral blood vessels. In selected cases, NPY was observed in nerve fibers in close association with intratumoral blood vessels and in the vicinity of tumor cells, while no PYY or PP was detected immunohistochemically in these sites. NPY receptors on renal tumor cells and tumor blood vessels may therefore be the molecular targets of endogenous NPY released by intratumoral nerve fibers. With regard to clinical applications, NPY receptors may act as in vivo targets for receptor-directed therapy of RCCs and nephroblastomas for which alternative therapeutic approaches are still required. ' 2005 Wiley-Liss, Inc.Key words: NPY receptor; renal cell carcinoma; nephroblastoma; receptor autoradiography Peptide hormone receptors are overexpressed in a wide variety of human tumors.1 Like other cell surface molecules, these receptors become increasingly important for clinical applications. In particular, they allow receptor-targeted tumor imaging and therapy with corresponding peptide hormone analogs. For instance, scintigraphy using the somatostatin analog Octreoscan is highly sensitive at detecting gastroenteropancreatic neuroendocrine tumors which express somatostatin receptors in high amounts.2,3 Moreover, targeted radiotherapy of these tumors with 90 Y-or 177 Lu-labeled somatostatin analogs is also promising. 4,5 Another peptide hormone receptor family with a potential future role in this field is the NPY receptor family. It belongs to the G protein-coupled receptor superfamily and comprises various subtypes. Subtypes Y1, Y2, Y4 and Y5 are expressed in humans. 6 They are present mainly in the central and peripheral nervous systems as well as other tissues, such as the cardiovascular system. Their physiologic ligands are the neurotransmitter NPY and the 2 hormones PYY and PP. Among many other sites, NPY has been localized to perivascular nerves in the human kidney. 7 NPY receptors may also play a role in human neoplasia. High incidence rates of subtypes Y1 and Y2 were found in tumors related to steroid hormone metabolism (adrenal cortical tumors, ovarian sex cord-stromal tumors, breast carcinomas), 8,9 in neuroendocrine tumors (pheochromocytomas and paragangliomas) 10

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Controversies and advances in the management of Wilms' tumour

Cited by 77 publications

References 30 publications

Cystic Nephroma, Cystic Partially Differentiated Nephroblastoma and Cystic Wilms’ Tumor in Children: A Spectrum with Therapeutic Dilemmas

Cystic Nephroma, Cystic Partially Differentiated Nephroblastoma and Cystic Wilms’ Tumor in Children: A Spectrum with Therapeutic Dilemmas

KIT, PDGFRα and EGFR analysis in nephroblastoma

Neuropeptide Y receptors in renal cell carcinomas and nephroblastomas

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