PURPOSE

Wilms tumor (WT) management has evolved into a multimodality paradigm that includes radiotherapy (RT), usually as an adjuvant or consolidative modality. Protocols are refined to maximize cure and compliance while minimizing acute toxicity and long-term effects. RT technique and timing are two factors that could improve these outcomes. We reviewed the evidence on survival and toxicity outcomes among WT patients with conventional versus advanced RT techniques and early versus delayed RT to inform a Department of Health (DOH) commissioned guideline.

MATERIALS AND METHODS

We systematically searched PubMed, EuropePMC, EBSCOHost, HERDIN, systematic review and clinical trial registries and official websites of scientific societies for relevant publications and grey literature. Eligibility screening, risk-of-bias assessment and data extraction were performed using a single-reviewer approach. Given the study and data heterogeneity, only a qualitative synthesis was performed. Certainty of evidence assessment was done using the GRADE approach.

RESULTS

We screened 314 studies and included seven in the review, including a phase 1/2 trial and six retrospective studies, all from first-world countries (US, France, Netherlands), except one from a newly industrialized country (Brazil). The certainty of evidence on the survival and toxicity outcomes with advanced RT techniques was very low. Moderate-certainty evidence supports that giving RT >14 days after surgery leads to increased mortality.

CONCLUSION

Current evidence does not support the routine use of advanced RT techniques; proper contextualization is necessary. Tertiary centers managing WT should strive to administer RT within 14 days after surgery whenever possible.

Wilms Tumor ; Nephroblastoma ; Radiotherapy ; Radiotherapy, Intensity-modulated ; Survival ; Toxicity

Chromosome Deletion ; Humans ; Kidney Neoplasms ; WAGR Syndrome/genetics* ; Wilms Tumor

Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome is caused by deletion of chromosome 11p13, including the Wilms' tumor (WT1) and aniridia gene (PAX6) loci. Here, we report the first case of WAGR syndrome in Korea; the patient was a 2-year-old girl with bilateral aniridia from birth who presented with abdominal distention and mental retardation. Cytogenetically, she had deletion of chromosome 11p11.2-13. Bilateral Wilms' tumors were successfully treated by chemotherapy and surgery. She has been tumor-free for 19 months off chemotherapy with preserved renal function.
Aniridia ; Humans ; Intellectual Disability ; Korea ; Parturition ; Preschool Child ; WAGR Syndrome ; Wilms Tumor

Congenital aniridia is a rare ocular malformation that presents with severe hypoplasia of the iris and various ocular manifestations. Most cases of congenital aniridia are known to be related to mutations in the paired box gene-6 (PAX6), which is an essential gene in eye development. Herein, we report a familial case of autosomal dominant congenital aniridia with four affected members in 3 consecutive generations and describe the detailed ophthalmologic findings for one of these members. As expected, mutational analysis revealed a nonsense mutation (p.Ser122*) in the PAX6 gene. Thus, our findings reiterate the importance of PAX6 mutations in congenital aniridia.
Aniridia* ; Codon, Nonsense ; Family Characteristics ; Genes, Essential ; Humans ; Iris ; WAGR Syndrome ; Wilms Tumor

WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome is a rare contiguous gene deletion syndrome caused by deleting genes including WT1 and PAX6 genes in 11p13 region, which is characterized by Wilms tumor, aniridia, genitourinary abnormalities, and intellectual disability. We report the clinical and cytogenetic characteristics of one Korean patient with WAGR syndrome. The patient shows bilateral sporadic aniridia and genital anomalies at 2 months of age. A heterozygous 14.5 Mb interstitial deletion of 11p14.3p12 region was detected by array comparative genomic hybridization. At 2 years and 10 months of age, Wilms tumor is found through regularly abdominal ultrasonography and treated by chemotherapy, radiation therapy and surgery.
Aniridia ; Comparative Genomic Hybridization ; Cytogenetics ; Drug Therapy ; Gene Deletion ; Humans ; Intellectual Disability ; Ultrasonography ; Urogenital Abnormalities ; WAGR Syndrome* ; Wilms Tumor*

Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, Pair 11 ; Humans ; Magnetic Resonance Imaging ; Male ; WAGR Syndrome ; diagnosis ; genetics ; pathology ; Wilms Tumor ; genetics ; pathology ; surgery

Drash syndrome, which was first reported by Denys et al. in 1967 is a complex disorder which associates a nephropathy, Wilms' tumor, and male pseudohermaphroditism. The common denominator is a nephropathy. The nephropathy may be associated with either genital abnormalities or Wilms' tumor, and these associations are called incomplete form of Drash syndrome. This syndrome appears early in life and the first sign usually is genital ambiguity. The nephropathy presents with proteinuria, hematuria and hypertension, and eventually progresses to end stage renal failure. Renal biopsy may reveal a variety of glomerular and interstitial changes. Wilms' tumor may appear as s mass on ultrasound or it may not be recognized until nephrectomy or even autopsy. We report on a boy with nephropathy and genital abnormalities. A nephrotic syndrome with hypertension was present when first seen at 15 days of age. The karyotype was 46, XY and external genitalia was ambiguous. The nephrotic syndrome and signs of renal insufficiency persisted and he died at the age of 40 days. Histopathologic findings of kidney at autopsy revealed those of diffuse mesangial sclerosis. The case was presented with brief review of literatures.
46, XY Disorders of Sex Development ; Autopsy ; Biopsy ; Denys-Drash Syndrome* ; Disorders of Sex Development ; Genitalia ; Hematuria ; Humans ; Hypertension ; Karyotype ; Kidney ; Male ; Nephrectomy ; Nephrotic Syndrome ; Proteinuria ; Renal Insufficiency ; Sclerosis ; Ultrasonography ; Wilms Tumor

OBJECTIVETo study the clinical and pathological features of Denys-Drash syndrome (DDS).

METHODThree DDS cases who were treated in our department from December 2009 to June 2011 were subjected to this study by reviewing of literature.

RESULTBoth case 1 and case 2 were female, with karyotype 46, XX. Case 3 was male with bilateral cryptorchidism. The ages of nephropathy onset of the three cases were 1 year and 9 months, 2 years and 8 moths, and 3 months respectively. Proteinuria in case 2 and case 3 were evidenced to be resistant to steroid. Case 1 was partially responsive to tacrolimus, plasma albumin and cholesterol were improved, although proteinuria was persistent after Tacrolimus was administered. Remission was achieved in case 2 after administration of cyclosporine A and later tacrolimus, and her renal function remains normal till present (4 years and 9 months). Residue renal histology revealed diffused mesangial sclerosis (DMS) in all three patients. All of the three patients had developed right unilateral Wilms tumor. A novel WT1 missense mutation exon 9 c.1213C > G was detected in case 1. WT1 exon 9 c.1168C > T nonsense mutation and exon 8 c.1130A > T missense mutation were detected in case 2 and case 3, respectively.

CONCLUSIONThe clinical manifestation of nephropathy in DDS is variable. The majority present with early onset nephropathy and reach renal failure before the age of 4 years. But in a few patients, nephropathy can also be present much later and progress slowly. Proteinuria in DDS is resistant to steroid but is responsive to calcineurin inhibitors, including Cyclosporine A. The effectiveness of tacrolimus was also observed in this study. DDS is evidently caused by WT1 mutation. DMS is the characteristic renal pathological change in DDS.

Cyclosporine ; therapeutic use ; Denys-Drash Syndrome ; drug therapy ; genetics ; pathology ; Fatal Outcome ; Female ; Genes, Wilms Tumor ; Heterozygote ; Humans ; Infant ; Male ; Mutation ; Nephrotic Syndrome ; drug therapy ; genetics ; pathology ; Proteinuria ; drug therapy ; Sclerosis ; drug therapy ; genetics ; pathology ; Tacrolimus ; therapeutic use ; Treatment Outcome ; WT1 Proteins ; genetics ; Wilms Tumor ; drug therapy ; genetics ; pathology

Twelve cases of Wilms tumor proved by histological examination are recorded and the literature is reviewed because of the paucity of the reports on this neoplasm occurring in Koreans. The average age incidence was 4.2 years; the youngest patient was 9 months of age and the oldest one was 23 years of age. Three fourths of the patients were children under three years of age. Seven were males and five were females. The incidence of Wilms tumor among all renal cancers was 57 per cent and this is much higher than that reported in the foreign literature. This high incidence may be attributed to a much higher incidence of this neoplasm among Korean infants and children. The most prominent clinical finding was abdominal swelling and a palpable mass, but fever, hypertension, irritability, hematuria and cough were other common symptoms. Hypertension was encountered in 89 per cent of the cases. The common laboratory findings were anemia, leukocytosis, increased erythrocyte sedimentation rate and proteinuria. Gross and microscopic findings are described. All specimens were much 1arger than the normal kidney. The largest specimen, kidney plus tumor, weighed 1,800 gm. The tumors were composed of well formed tubules. solid islands of dark staining undifferentiated cells presumably of mesoblastic origin and various elements of stromal cells. The proportion of each element varied markedly from case to case and also in different parts of the same tumor. Nests of squamous cells, some of them forming pearls, and cystic structures identical with epidermal cysts were observed in three of our 12 cases, but unequivocal striated muscle cells as well as bone or cartilage were found in none of our cases. Some nests of squamous cells observed in tubules suggested that they were derived from metaplasia of the lining epithelium.
Adolescent ; Adult ; Child ; Child, Preschool ; Human ; Korea ; Middle Aged ; Nephrectomy ; Nephroblastoma/*epidemiology/pathology ; Urography

OBJECTIVE: To investigate the role of NOV/CCN3 in regulating the proliferation of mesenchymal stem cells (MSCs) and its regulatory mechanism and assess the value of CCN3 as a proliferative factor in bone tissue engineering. METHODS: Mouse embryonic fibroblasts (MEFs) were used as the MSC model, in which CCN3 expression was up-regulated and downregulated by transfection with the recombinant adenovirus vectors Ad-CCN3 and Ad-siCCN3, respectively. Flow cytometry was used to analyze the changes in cell cycle and apoptosis of the transfected cells. Western blotting was used to detect the expression levels of the proliferation indicators (PCNA, cyclin E, and cyclin B1) and the apoptosis indicators (Bax and Bcl-2) to assess the effect of modulation of CCN3 expression on MEF proliferation and apoptosis. CCN3 protein secretion by the cells was detected using ELISA. RT-qPCR and Western blotting were employed to analyze the changes in the expressions of Notch1, ligand DLL1, the downstream key proteins or genes (Hey1, P300, H3K9) and MAPK pathway-related proteins ERK1+2 and p-ERK1+2. RESULTS: Flow cytometry showed that compared with the control cells, MEFs transfected with Ad-CCN3 exhibited significantly increased cell proliferation index ( CONCLUSIONS CCN3 over-expression promotes the proliferation and inhibits apoptosis of MEFs possibly by inhibiting the classical Notch signaling pathway and activating the MAPK pathway
Animals ; Apoptosis ; Cell Cycle ; Cell Proliferation ; Fibroblasts ; Mice ; Nephroblastoma Overexpressed Protein