Purpose: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. Materials and Methods: From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. Results: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). Conclusion The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Background: Infants and very young children with malignant brain tumors have a poorer survival and a higher risk for neurologic deficits. The present study evaluated the feasibility and effectiveness of multimodal treatment including tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in minimizing use of radiotherapy (RT) in very young children with non-metastatic malignant brain tumors. Methods: Twenty consecutive patients younger than 3 years were enrolled between 2004 and 2017. Tandem HDCT/auto-SCT was performed after six cycles of induction chemotherapy.Local RT was administered only to patients with post-operative gross residual tumor at older than 3 years. Since September 2015, early post-operative local RT for patients with atypical teratoid/rhabdoid tumor or primitive neuroectodermal tumor was administered. Results: All 20 enrolled patients underwent the first HDCT/auto-SCT, and 18 proceeded to the second. Two patients died from toxicity during the second HDCT/auto-SCT, and four patients experienced relapse/progression (one localized and three metastatic), three of whom remained alive after salvage treatment including RT. A total of 17 patients remained alive at a median 7.8 (range, 2.5−15.7) years from diagnosis. Nine survivors received no RT, six survivors received local RT alone, and two survivors who experienced metastatic relapse after tandem HDCT/auto-SCT received both local and craniospinal RT. The 5-year overall, eventfree, and craniospinal RT-free survival rates were 85.0% ± 8.0%, 70.0% ± 10.2%, and 75.0% ± 9.7%, respectively. Neuroendocrine and neurocognitive functions evaluated 5 years after tandem HDCT/auto-SCT were acceptable. Conclusion Our results suggest that non-metastatic malignant brain tumors in very young children could be treated with multimodal therapy including tandem HDCT/auto-SCT while minimizing RT, particularly craniospinal RT.

BACKGROUND: Neurotrophin-3 (NT-3), a member of the NT family, has only been considered an ancillary compound that provides anti-apoptotic benefits by inactivating tropomyosin receptor kinase C (TrkC)-induced apoptotic signals. However, little is known about the clinical relevance of NT-3 expression itself in neuroblastoma. The purpose of this study was to assess NT-3 expression in patients with neuroblastoma and its relevance to clinicopathologic findings and treatment outcomes. METHODS: In this study, expression of NT-3 and TrkC was analyzed using immunohistochemistry in 240 patients with newly diagnosed neuroblastoma. RESULTS: The results of the study revealed that NT-3 expression was associated with older age at diagnosis, localized tumors, and more differentiated tumors but was not associated with early treatment response (degree of residual tumor volume after three cycles of chemotherapy) and progression-free survival (PFS). However, when analysis was confined to patients with MYCN amplified tumors, NT-3 expression was associated with better early treatment response with borderline significance (P = 0.092) and higher PFS (86.9% vs. 58.2%; P = 0.044). In multivariate analysis in patients with MYCN amplified tumors, NT-3 was independent prognostic factor (hazard ratio, 0.246; 95% confidence interval, 0.061–0.997; P = 0.050). In another subgroup analysis, the early treatment response was better if NT-3 was expressed in patients without TrkC expression (P = 0.053) while it was poorer in patients with TrkC expression (P = 0.023). CONCLUSION: This study suggests that NT-3 expression in neuroblastoma has its own clinical significance independent of TrkC expression, and its prognostic significance differs depending on the status of MYCN amplification and/or TrkC expression.
Diagnosis ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Multivariate Analysis ; Neoplasm, Residual ; Neuroblastoma ; Phosphotransferases ; Tropomyosin

BACKGROUND: To evaluate the value of random urinary vanillylmandelic acid (VMA) as a surrogate marker for monitoring tumor response and predicting outcome in patients with neuroblastoma (NB). METHODS: Medical records of 91 patients newly diagnosed with NB at the Samsung Medical Center between June 2014 and August 2017 were reviewed. Clinical associations and other prognostic factors, including age at diagnosis, stage, pathologic subtype, MYCN amplification, and other cytogenetic aberrations, were analyzed. Furthermore, the significance of random urinary VMA level in predicting outcome and tumor response was also evaluated. RESULTS: The median random urinary VMA level at diagnosis was 27.9 (range: 1.7–600) mg/g creatinine. Abdominal primary site, male sex, advanced stage, less differentiated pathology (poorly differentiated, undifferentiated), 11q deletion, and high-risk tumor were associated with a higher VMA level at diagnosis. The VMA level decreased during chemotherapy (28.4%, 16.9%, and 9.6% of the VMA level at diagnosis after 3, 6, and 9 cycles of chemotherapy, respectively). A higher VMA level at diagnosis tends to be associated with a better overall survival in high-risk patients with borderline significance (58.3±18.6% vs. 76.5±13.4%, P=0.050). However, in the multivariate analysis, the VMA level was not a significant predictor of survival. A slower reduction in VMA level during chemotherapy was not associated with a worse overall survival. However, event free survival was significantly better in the rapid responder group. CONCLUSION: A higher VMA level was associated with high-risk features at diagnosis of NB. Random urinary VMA is a valuable marker for monitoring NB response during chemotherapy.
Biomarkers ; Chromosome Aberrations ; Creatinine ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Humans ; Male ; Medical Records ; Multivariate Analysis ; Neuroblastoma* ; Pathology ; Prognosis ; Vanilmandelic Acid*

BACKGROUND: By estimating the survival rates and exploring prognostic factors in pediatric patients with relapsed or progressed solid tumors, our purpose was to generate background data for future studies. METHODS: We reviewed the medical records of 258 patients with solid tumors who experienced relapse/progression and received subsequent salvage treatment between 1996 and 2016. RESULTS: A total of 60 patients remained progression-free during first-line salvage treatment, while the remaining 198 patients experienced relapse/progression again; 149 underwent second-line salvage treatment. A total of 76 patients underwent high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), and 44 patients received allogeneic SCT. The 10-year progression-free survival (PFS) and overall survival (OS) from relapse/progression were 18.4% ± 2.7% and 24.5% ± 3.0%, respectively. Survival rates were relatively higher in patients with anaplastic ependymoma, initially non-high-risk neuroblastoma, osteosarcoma, Wilms tumor and retinoblastoma. A multivariate analysis showed that relapse/progression during initial treatment, metastatic relapse/progression, and impossible debulking surgery were independent poor prognostic factors for both PFS and OS. Patients who exhibited a complete response or partial response during conventional salvage treatment showed significantly higher survival after SCT than those with stable disease or progressive disease (10-year OS: 54.8% ± 7.0% vs. 7.0% ± 3.5%, P < 0.001). CONCLUSION: The prognosis of relapsed/progressed pediatric solid tumors still remains unsatisfactory. New, effective treatment strategies are needed to overcome limitations of current approaches. Hopefully, the background data generated herein will be used in future clinical trials involving patients with relapsed/progressed solid tumors.
Adolescent* ; Child* ; Disease-Free Survival ; Drug Therapy ; Ependymoma ; Humans ; Medical Records ; Multivariate Analysis ; Neuroblastoma ; Osteosarcoma ; Prognosis ; Recurrence ; Retinoblastoma ; Salvage Therapy ; Stem Cell Transplantation ; Survival Rate ; Wilms Tumor

The voltage-gated Na channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.
Animals ; Antibodies, Monoclonal ; therapeutic use ; Biotin ; metabolism ; Cells, Cultured ; Disease Models, Animal ; Female ; Ganglia, Spinal ; cytology ; HEK293 Cells ; Humans ; Hybridomas ; chemistry ; Hyperalgesia ; drug therapy ; Male ; Mice ; Mice, Inbred C57BL ; NAV1.5 Voltage-Gated Sodium Channel ; metabolism ; NAV1.7 Voltage-Gated Sodium Channel ; chemistry ; immunology ; metabolism ; Neuralgia ; drug therapy ; metabolism ; Protein Binding ; drug effects ; Recombinant Proteins ; biosynthesis ; therapeutic use ; Sensory Receptor Cells ; drug effects ; physiology

OBJECTIVES: We conducted a systematic review and meta-analysis to summarize current evidence regarding the association of parity and duration of breastfeeding with the risk of epithelial ovarian cancer (EOC). METHODS: A systematic search of relevant studies published by December 31, 2015 was performed in PubMed and EMBASE. A random-effect model was used to obtain the summary relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Thirty-two studies had parity categories of 1, 2, and ≥3. The summary RRs for EOC were 0.72 (95% CI, 0.65 to 0.79), 0.57 (95% CI, 0.49 to 0.65), and 0.46 (95% CI, 0.41 to 0.52), respectively. Small to moderate heterogeneity was observed for one birth (p<0.01; Q=59.46; I²=47.9%). Fifteen studies had breastfeeding categories of <6 months, 6-12 months, and >13 months. The summary RRs were 0.79 (95% CI, 0.72 to 0.87), 0.72 (95% CI, 0.64 to 0.81), and 0.67 (95% CI, 0.56 to 0.79), respectively. Only small heterogeneity was observed for <6 months of breastfeeding (p=0.17; Q=18.79, I²=25.5%). Compared to nulliparous women with no history of breastfeeding, the joint effects of two births and <6 months of breastfeeding resulted in a 0.5-fold reduced risk for EOC. CONCLUSIONS: The first birth and breastfeeding for <6 months were associated with significant reductions in EOC risk.
Birth Order ; Breast Feeding* ; Female ; Humans ; Joints ; Ovarian Neoplasms* ; Parity* ; Parturition ; Population Characteristics ; Reproduction ; Risk Factors

Neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood and is characterized by a wide range of clinical behaviors. Amplification of MYCN is a well-known poor prognostic factor in NB patients. As the MYCN amplification status is usually tested using tumor specimens, lengthy and invasive procedures are unavoidable. To evaluate the possibility of detecting MYCN amplification without invasive procedure, we performed conventional polymerase chain reaction (PCR) analysis to identify MYCN amplification using the preserved serum DNA. PCR of serum DNA was done in 105 NB patients whose MYCN status had been confirmed by fluorescence in situ hybridization. MYCN amplification was evaluated as the ratio of signal intensities between MYCN and NAGK (M/N ratio). When regarding the tissue FISH results as a reference, 10 patients had MYCN-amplified (MNA) NB, and 95 had non-MNA NB. The M/N ratio of the MNA group (median 2.56, range 1.01-3.58) was significantly higher than that of the non-MNA group (median 0.97, range 0.67-5.18) (P < 0.001). In the receiver operating characteristic curve analysis, the area under the curve was 0.957 (95% confidence interval 0.898-1.000; P < 0.001), and it showed 90.9% sensitivity and 97.9% specificity with the selected cut-off value set as 1.6. The detection of MYCN amplification using conventional PCR analysis of serum samples seems to be a simple and promising method to evaluate the MYCN status of NB patients. Further study with a larger set of patients is needed to confirm the accuracy of this result.
DNA* ; Fluorescence ; Humans ; In Situ Hybridization ; Methods ; Neuroblastoma ; Polymerase Chain Reaction* ; ROC Curve ; Sensitivity and Specificity

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