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Nature Reviews. Urology Nov 2018On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology...
On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP-RTSG) has developed a new study protocol for paediatric renal tumours: the UMBRELLA SIOP-RTSG 2016 protocol (the UMBRELLA protocol). Currently, the overall outcomes of patients with Wilms tumour are excellent, but subgroups with poor prognosis and increased relapse rates still exist. The identification of these subgroups is of utmost importance to improve treatment stratification, which might lead to reduction of the direct and late effects of chemotherapy. The UMBRELLA protocol aims to validate new prognostic factors, such as blastemal tumour volume and molecular markers, to further improve outcome. To achieve this aim, large, international, high-quality databases are needed, which dictate optimization and international harmonization of specimen handling and comprehensive sampling of biological material, refine definitions and improve logistics for expert review. To promote broad implementation of the UMBRELLA protocol, the updated SIOP-RTSG pathology and molecular biology protocol for Wilms tumours has been outlined, which is a consensus from the SIOP-RTSG pathology panel.
Topics: Biomarkers, Tumor; Biopsy; Child; Humans; Kidney; Kidney Neoplasms; Neoplasm Staging; Prognosis; Specimen Handling; Wilms Tumor
PubMed: 30310143
DOI: 10.1038/s41585-018-0100-3 -
Current Opinion in Pediatrics Feb 2021The treatment of Wilms tumor is one of the great achievements in the field of oncology. One of the key success factors has been improved risk stratification, enabling... (Review)
Review
PURPOSE OF REVIEW
The treatment of Wilms tumor is one of the great achievements in the field of oncology. One of the key success factors has been improved risk stratification, enabling augmentation or reduction of therapy depending on a patient's risk of relapse. This article highlights the evolution of clinical and biological prognostic markers that have been applied in the treatment of Wilms tumor.
RECENT FINDINGS
Historically, tumor stage and histology were the sole determinants of Wilms tumor treatment. Recent clinical trials conducted by the Children's Oncology Group (COG) and the International Society of Pediatric Oncology (SIOP) Renal Tumor Study Group have expanded the menu of prognostic factors to include histologic and volumetric response to therapy and tumor-specific loss of heterozygosity (LOH) at chromosomes 1p and 16q. Augmentation of therapy has been able to overcome the adverse risk factors. An emerging prognostic marker is chromosome 1q gain, will be incorporated into future clinical trials.
SUMMARY
The application of new clinical and biological prognostic factors has created unprecedented ability to tailor therapy for Wilms tumor, accompanied with improved outcomes. Current and future trials will continue to enhance precision medicine for Wilms tumor.
Topics: Child; Humans; Kidney Neoplasms; Neoplasm Recurrence, Local; Neoplasm Staging; Risk Assessment; Wilms Tumor
PubMed: 33394739
DOI: 10.1097/MOP.0000000000000988 -
Journal of Veterinary Internal Medicine 2006Primary renal tumors are diagnosed uncommonly in dogs.
BACKGROUND
Primary renal tumors are diagnosed uncommonly in dogs.
HYPOTHESIS
Signs and survival will differ among different categories of primary renal tumors.
ANIMALS
Data were collected from the medical records of 82 dogs with primary renal tumors diagnosed by examination of tissue obtained by ultrasound-guided biopsy, needle aspiration, surgery, or at postmortem examination.
METHODS
This was a multi-institutional, retrospective study.
RESULTS
Forty-nine dogs had carcinomas, 28 had sarcomas, and 5 had nephroblastomas. The dogs were geriatric (mean 8.1 years; range: 1-17) with a weight of 24.9 kg (range: 4.5-80). Tumors occurred with equal frequency in each kidney with 4% occurring bilaterally. Initial signs included one or more of hematuria, inappetance, lethargy. weight loss, or a palpable abdominal mass. Pain was reported more frequently in dogs with sarcomas (5/28). The most common hematologic abnormalities were neutrophilia (22/63), anemia (21/64), and thrombocytopenia (6/68). Polycythemia was present in 3 dogs and resolved with treatment. Hematuria (28/49), pyuria (26/49), proteinuria (24/50), and isosthenuria (20/56) were the most frequently observed abnormalities on urinalysis. Pulmonary metastases were noted on thoracic radiographs in 16% of dogs at diagnosis. Seventy-seven percent of dogs had metastatic disease at the time of death. Median survival for dogs with carcinomas was 16 months (range 0-59 months), for dogs with sarcomas 9 months (range 0-70 months), and for dogs with nephroblastomas 6 months (range 0-6 months).
CONCLUSIONS AND CLINICAL IMPORTANCE
Primary renal tumors in dogs are generally highly malignant with surgery being the only treatment that improves survival.
Topics: Animals; Carcinoma; Dog Diseases; Dogs; Female; Kidney Neoplasms; Male; Retrospective Studies; Sarcoma; Statistics, Nonparametric; Survival Analysis; Wilms Tumor
PubMed: 17063709
DOI: 10.1892/0891-6640(2006)20[1155:prnod]2.0.co;2 -
Cancer Imaging : the Official... Apr 2015Neuroblastoma (NBL) is the most common extra-cranial tumour in childhood. It can present as an abdominal mass, but is usually metastatic at diagnosis so the... (Review)
Review
Neuroblastoma (NBL) is the most common extra-cranial tumour in childhood. It can present as an abdominal mass, but is usually metastatic at diagnosis so the symptomatology can be varied. Nephroblastoma, also more commonly known as a Wilms tumour, is the commonest renal tumour in childhood and more typically presents as abdominal pathology with few constitutional symptoms, although rarely haematuria can be a presenting feature. The pathophysiology and clinical aspects of both tumours including associated risk factors and pathologies are discussed. Oncogenetics and chromosomal abnormalities are increasingly recognised as important prognostic indicators and their impact on initial management is considered. Imaging plays a pivotal role in terms of diagnosis and recent imaging advances mean that radiology has an increasingly crucial role in the management pathway. The use of image defined risk factors in neuroblastoma has begun to dramatically change how this tumour is characterised pre-operatively. The National Wilms Tumour Study Group have comprehensively staged Wilms tumours and this is reviewed as it impacts significantly on management. The use of contrast-enhanced MRI and diffusion-weighted sequences have further served to augment the information available to the clinical team during initial assessment of both neuroblastomas and Wilms tumours. The differences in management strategies are outlined. This paper therefore aims to provide a comprehensive update on these two common paediatric tumours with a particular emphasis on the current crucial role played by imaging.
Topics: Child; Diffusion Magnetic Resonance Imaging; Humans; Kidney Neoplasms; Magnetic Resonance Imaging; Neoplasm Invasiveness; Neoplasm Staging; Neuroblastoma; Radiography; Risk Factors; Wilms Tumor
PubMed: 25889326
DOI: 10.1186/s40644-015-0040-6 -
Journal of B.U.ON. : Official Journal... 2020This study aimed to explore the expression changes of microRNA (miR)-140-5p and miR-370 in nephroblastoma and its effect on the proliferative ability of nephroblastoma...
PURPOSE
This study aimed to explore the expression changes of microRNA (miR)-140-5p and miR-370 in nephroblastoma and its effect on the proliferative ability of nephroblastoma WT_CLS1 and SK-NEP-1 cells.
METHODS
The expression levels of miR-140-5p and miR-370 was detected by quantitative real-time PCR (qRT-PCR) in cancer tissues and normal adjacent tissues which were collected from 60 patients with nephroblastoma. Expression vectors of miR-140-5p and miR-370 were constructed, and transient transfection of human nephroblastoma cell lines WT_CLS1 and SK-NEP-1 was carried out in vitro. There were three groups of the two genes: Blank cell group (blank group); Gene transfection group (miR-490-5p group, miR-370 group); and No-load transfection group (NLTF group). The proliferative ability of WT_CLS1 and SK-NEP-1 cells was detected by MTT assay.
RESULTS
The results of miR-140-5p and miR-370 detected by qRT-PCR showed that in cancer tissues the expression level of miR-140-5p was significantly lower than that in adjacent tissues, and the level of miR-370 was significantly higher than that in adjacent tissues, and the difference was statistically significant (p<0.001). The proliferation of WT_CLS1 and SK-NEP-1 cells in miR-140-5p group was significantly lower than that in NLTF group (p<0.05), while the proliferation of WT_CLS1 and SK-NEP-1 cells in miR-370 group was significantly higher than that in NLTF group (p<0.05).
CONCLUSION
miR-140-5p is lowly expressed and miR-370 is highly expressed in nephroblastoma tissues; miR-370 can promote the proliferation of WT-CLS1 cells in nephroblastoma, and miR-140-5p can inhibit their proliferation and it may become a new target for the treatment of nephroblastoma in the future.
Topics: Adolescent; Adult; Cell Proliferation; Child; Child, Preschool; Female; Humans; Infant; Kidney Neoplasms; Male; MicroRNAs; Transfection; Wilms Tumor; Young Adult
PubMed: 33099960
DOI: No ID Found -
JCO Global Oncology Jul 2022Nephroblastoma is a highly curable pediatric cancer that requires multidisciplinary care. Few reports have assessed long-term treatment outcomes in low-resource settings...
PURPOSE
Nephroblastoma is a highly curable pediatric cancer that requires multidisciplinary care. Few reports have assessed long-term treatment outcomes in low-resource settings using a task-shifting model of care. We report outcomes of a large cohort and factors associated with survival.
METHODS
We performed a retrospective chart review of all patients with nephroblastoma presenting to the Butaro Cancer Center of Excellence in Rwanda between July 2012 and June 2018.
RESULTS
In total, 136 patients were identified and treated according to International Society of Pediatric Oncology guidelines for low-income settings. Median age at diagnosis was 39.7 months (interquartile range, 25.3-61.8 months); 56.6% were female. Sixty-one (44.9%) patients presented with stage I-III disease, 35 (25.7%) with stage IV disease, and 6 (4.4%) with stage V disease; the remainder were unstaged (n = 34; 25.0%). Most patients completed surgery (n = 97; 71.3%) and postoperative chemotherapy (n = 82; 60.2%); 17 patients received radiotherapy. With a median follow-up time of 18.1 months, 44.9% of patients were alive, 41.9% had died, 8.8% were lost to follow-up, and 4.4% were referred for palliative care or declined further care at the end of the study. Three-year overall survival was 57.5% (95% CI, 48.1 to 65.8) for the entire cohort, and 80.1% (95% CI, 66.8 to 88.5) and 44.0% (95% CI, 26.8 to 60.0) for stages I-III and IV-V, respectively.
CONCLUSION
We demonstrate that patients with nephroblastoma can be successfully treated in a low-resource setting. Survival remains lower than in high-income countries, in part due to early deaths, contributing to approximately 30% of patients not being medically able to receive surgical intervention. Next steps include the development of strategies that focus on earlier diagnosis, supportive care during the early phases of therapy, and efficient and timely transitions between specialties for multimodal care.
Topics: Child; Female; Humans; Male; Kidney Neoplasms; Poverty; Retrospective Studies; Treatment Outcome; Wilms Tumor; Child, Preschool
PubMed: 35820081
DOI: 10.1200/GO.22.00036 -
Advanced Science (Weinheim,... Jul 2023A nephrogenic progenitor cell (NP) with cancer stem cell characteristics driving Wilms tumor (WT) using spatial transcriptomics, bulk and single cell RNA sequencing, and...
A nephrogenic progenitor cell (NP) with cancer stem cell characteristics driving Wilms tumor (WT) using spatial transcriptomics, bulk and single cell RNA sequencing, and complementary in vitro and transplantation experiments is identified and characterized. NP from WT samples with NP from the developing human kidney is compared. Cells expressing SIX2 and CITED1 fulfill cancer stem cell criteria by reliably recapitulating WT in transplantation studies. It is shown that self-renewal versus differentiation in SIX2+CITED1+ cells is regulated by the interplay between integrins ITGβ1 and ITGβ4. The spatial transcriptomic analysis defines gene expression maps of SIX2+CITED1+ cells in WT samples and identifies the interactive gene networks involved in WT development. These studies define SIX2+CITED1+ cells as the nephrogenic-like cancer stem cells of WT and points to the renal developmental transcriptome changes as a possible driver in regulating WT formation and progression.
Topics: Humans; Transcription Factors; Wilms Tumor; Kidney; Neoplastic Stem Cells; Kidney Neoplasms
PubMed: 37114795
DOI: 10.1002/advs.202206787 -
European Review For Medical and... Oct 2017To investigate the correlation of regulator of G-protein signaling 4 (RGS4) and P16 expressions with pediatric nephroblastoma and its significance on prognosis.
OBJECTIVE
To investigate the correlation of regulator of G-protein signaling 4 (RGS4) and P16 expressions with pediatric nephroblastoma and its significance on prognosis.
PATIENTS AND METHODS
A total of 80 children with primary nephroblastoma who underwent surgical resection in our hospital from March 2009 to March 2012 were selected as objects of study. The expressions of RGS4 and P16 in cancer and cancer-adjacent tissues of patients were detected by reverse transcription-polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry. All patients were followed up for 5 years. The relationship of RGS4 and P16 to nephroblastoma staging and patients' prognosis was analyzed.
RESULTS
The results of RT-PCR and Western blot displayed that the expressions of RGS4, P16 mRNA and protein in cancer tissue, were significantly lower than those in cancer-adjacent tissue (p < 0.05). Immunohistochemistry result revealed that the positive rates of RGS4 and P16 in cancer tissue were distinctly lower than those in cancer-adjacent tissue (76.54% vs. 34.32%, p < 0.05). RGS4 and P16 protein expressions were not associated with tumor, node metastasis (TNM) and pathological typing of nephroblastoma, but they were lowly expressed in patients with high metastasis (p < 0.05). The expressions of RGS4 and P16 were absent in pediatric nephroblastoma, and overall survival (OS) was significantly reduced (p < 0.05).
CONCLUSIONS
The absence of RGS4 and P16 in pediatric nephroblastoma tissue is correlated with poor prognosis of patients. RGS4 and P16 are of significance for the prognosis of pediatric nephroblastoma.
Topics: Child, Preschool; Cyclin-Dependent Kinase Inhibitor p16; Female; Humans; Immunohistochemistry; Kidney; Kidney Neoplasms; Male; Neoplasm Staging; Prognosis; RGS Proteins; Survival Rate; Wilms Tumor
PubMed: 29131258
DOI: No ID Found -
Advances in Pediatrics 2012Significant improvement has been made in the treatment of children with Wilms tumor. New protocols are in place designed to maintain a high rate of cure for these... (Review)
Review
Significant improvement has been made in the treatment of children with Wilms tumor. New protocols are in place designed to maintain a high rate of cure for these patients while minimizing toxicity, based on refinement of the risk-stratification system.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Humans; Kidney Neoplasms; Neoplasm Staging; Survival Rate; Wilms Tumor
PubMed: 22789581
DOI: 10.1016/j.yapd.2012.04.001 -
Pediatric Blood & Cancer May 2023Outcomes are excellent for the majority of patients with Wilms tumors (WT). However, there remain WT subgroups for which the survival rate is approximately 50% or lower.... (Review)
Review
Outcomes are excellent for the majority of patients with Wilms tumors (WT). However, there remain WT subgroups for which the survival rate is approximately 50% or lower. Acknowledging that the composition of this high-risk group has changed over time reflecting improvements in therapy, we introduce the authors' view of the historical and current approach to the classification and treatment of high-risk WT. For this review, we consider high-risk WT to include patients with newly diagnosed metastatic blastemal-type or diffuse anaplastic histology, those who relapse after having been initially treated with three or more different chemotherapeutics, or those who relapse more than once. In certain low- or low middle-income settings, socio-economic factors expand the definition of what constitutes a high-risk WT. As conventional therapies are inadequate to cure the majority of high-risk WT patients, advancement of laboratory and early-phase clinical investigations to identify active agents is urgently needed.
Topics: Humans; Kidney Neoplasms; Neoplasm Staging; Wilms Tumor; Prognosis; Recurrence
PubMed: 37096797
DOI: 10.1002/pbc.30342