Malignant Solid Tumors In Children Research Articles

Hepatomegaly as the first symptom of malignant solid tumors in children

Hepatomegaly as the first symptom of malignant solid tumors in children

Research progress of CfDNA quantitative analysis for malignant solid tumors in children

Circulating free DNA is DNA fragments in the blood, mainly from cell apoptosis, necrosis and release.Its content is significantly different in the bood of healthy human and malignant tumor patients, which is associated with tumor characteristics.This review will summarize the research progress of CfDNA quantitative analysis for malignant solid tumor and prospect the application value for children′s solid tumors. Key words: Circulating free DNA; Malignant solid tumor; Children

Legumain correlates with neuroblastoma differentiation and can be used in prodrug design.

Neuroblastoma (NB) is a highly malignant solid tumor in children. The cysteine endopeptidase legumain is expressed in adult solid tumors, but its expression in NB has not been examined. In this study, we assayed legumain expression in two NB cell lines and in microarrays of tumor tissues collected from 46 children with undifferentiated NB, differentiated NB, and ganglioneuroblastoma. Correlation analyses showed that legumain was expressed in all NB cell lines tested and that expression correlated with the degree of tumor differentiation. The efficacy, specificity, and toxicity of EMC-AANL-DOX, a novel doxorubicin-based legumain-activated prodrug, were then evaluated in mouse model of NB. Compared with DOX, EMC-AANL-DOX showed greater inhibition of tumor growth and a lower toxicity at high doses. Neither leukocyte or platelet counts nor renal function or cardiac anatomy differed significantly between the EMC-AANL-DOX and control groups (p>.05), suggesting that the prodrug caused minimal bone marrow depression and did not induce renal or cardiac damage. The good specificity and efficacy of EMC-AANL-DOX and low toxicity recommend its use in the treatment of NB. Correlation analyses of NB differentiation and legumain expression may reveal a novel anti-tumor-related functions of the drug and a new strategy for the treatment of pediatric solid tumors.

Study progress in early recognition and initial treatment before referral of childhood malignant solid tumors

Childhood malignant solid tumors exhibit a wide variety of vagueness signs and symptoms in the early stage, which are usually nonspecific, therefore the diagnosis of childhood malignant solid tumor can be challenging when the disease is in the early stage.As a result, the delay of diagnosis causes mistreatment, and which makes childhood malignant solid tumors become a leading cause of death in children.Physicians should recognize the early warning signs of childhood cancer, and a good clinical history and careful physical examination can help physicians determine whether the children have cancer and make referrals in time.Some children with possible cancers require immediate initial treatment before referral to be stabilized in order to make the referrals possible and increase the chance of receiving appropriate treatment in time and the possibility of being cured, saving more children with malignant solid tumors to the maximum extent. Key words: Childhood malignant solid tumors; Symptomatology; Early diagnosis; Initial treatment before referral

Detection methods of minimal residual disease in childhood malignant solid tumors

Despite that survival rates have been improved in childhood malignant solid tumors, progression during treatment or relapse after complete remission remain a major cause hindering patients from getting long-time survival.Minimal residual disease(MRD)is closely related to relapse of solid tumors.This review discusses the advance and value of various methods used in MRD detection, aiming to establish a stable and reliable method for MRD detection. Key words: Childhood malignant tumor; Minimal residual disease; Methodology

ピラルビシン(THP)の小児固形がんにおける保険適応外使用に関するアンケート調査の結果

ピラルビシン(THP)の小児固形がんにおける保険適応外使用に関するアンケート調査の結果

Adverse reactions of collection and return infusions of autologous peripheral blood stem cells in children with malignant solid tumors

Objective To study the adverse reactions of collection and return infusions of autologous periphe-ral blood stem cells (APBSC) in children with malignant solid tumors. Methods Thirty-eight cases' clinical data diagnosed as advanced malignant solid tumors in children by pathological examination were collected from September 2005 to November 2011 in Beijing Tongren Hospital (27 male patients and 11 female patients). All cases were given high-dose chemotherapy and APBSC transplantation(APBSCT). According to world health organization(WHO) stan-dard of the adverse reactions of chemotherapy and radiotherapy and the Bearman standard of the adverse reactions of APBSCT, cli-nical data of these cases were analyzed.The adverse reactions of collection and return infusions of APBSC were summarized. Results (1)Mononuclear cell (MNC) count of 38 cases was (5.6±2.2)×108/kg, and CD34+ cell counts was (3.8±2.6)×106/kg.MNC count or CD34+ cell count of 31 cases was conformed to the standards.The coincidence rate was 81.6% (31/38 cases). (2)On (12.3±3.1) days, 38 cases obtained bone marrow reconstruction after return infusions of APBSC.The correlation coefficient of CD34+ cells count and bone marrow reconstruction was rs=-0.634, and that was negatively correlated(P=0.001). (3)Adverse reactions during APBSC collection and return infusions; the most adverse reactions during APBSC collection were arrhythmia, hypotension, gastrointestinal reaction and thrombocytopenia, et al.The main adverse reactions during APBSC return infusions were hemoglobinuria, hypertension and gastrointestinal reaction.The occurring rate of hemoglobinuria was 100%, but urine color gradually returned to normal after they were given the hydration and alkalization.(4) Adverse reactions during bone marrow suppression after return infusions: 38 patients with high-dose chemotherapy on + 3 to + 14 d were presented with toxic side effects those including 19 cases in grade Ⅰ, 11 cases in grade Ⅱ, 5 cases in grade Ⅲ, and 3 cases in grade Ⅳ(but 1 case died in the 3 cases). On + 15 to + 22 d, 37 patients with high-dose chemotherapy, 33 cases showed no adverse reactions, and 2 cases in grade Ⅰ, 2 cases in grade Ⅱ.On + 23 to + 40 d, the adverse reactions of 37 cases with high-dose chemotherapy were corrected. Conclusion The adverse reactions of APBSC were transient and no organ damage was observed, which was safe and reliable. Key words: Solid tumor; Autologous peripheral blood stem cell transplantation; Chemotherapy; Adverse reactions; Child

COMPLEX RADIOLOGICAL DIAGNOSIS OF COMPLICATED WILMS' TUMOR

Wilms' tumor is the most common primary malignant renal tumor. It is paradigm for comprehensive treatment of malignant solid tumors in children. Typically, children with this disorder are initially seen with abdominal distention, palpable masses or due to fever of unknown origin. Atypical tumor symptoms can be caused by complications, making it difficult to diagnose the disease. We present three clinical cases of Wilms' tumor in young children. Emergency multidetector computed tomography and magnetic resonance imaging provided the surgeon with sufficient information to perform an urgent radical resection.

Significance of miR-885-5p in neuroblastoma outcome

Neuroblastoma is the most common extracranial malignant solid tumor in children. This disease displays a remarkable heterogeneity in clinical behavior, ranging from spontaneous regression to rapid progression and resistance to therapy. Recent evidence has shown that microRNAs are often involved in regulation of tumor development and progression. MiR-885-5p has a tumor suppressive role in neuroblastoma, interfe­ring with cell cycle progression and cell survival. MiR-885-5p leads to the accumulation of p53 protein and activates p53-mediated pathway of cell cycle arrest, resulting in upregulation of its targets. We have analyzed association of miR-885-5p expression in 58 neuroblastoma tumors with different clinical characteristics and disease outcome. In tumor samples of patients with unfavorable clinical characteristics lower miR-885-5p expression levels were observed. Event-free survival analysis showed that low miR-885-5p expression was tightly associated with a significantly poorer outcome than in those with high expression of miR-885-5p. In this study, evidence is presented on miR-885-5p dysregulation in neuroblastoma. As follows, along with other clinical features, it can be used as an independent prognostic and possibly therapeutic approach for optimization of neuroblastoma treatment.

Trends in incidence of childhood malignant solid tumors in Japan: Estimation based on hospital-based registration

Background/PurposeIn Japan, an increase in hepatoblastoma with low birth weight has become evident since the 1990s, and there is concern about a possible increase in unfavorable neuroblastomas after the cessation of mass screening in 2004. MethodsThe trends in incidence of malignant solid tumors in children younger than 15years of age were inferred by evaluating registration incidence in the registry of the Japanese Society of Pediatric Surgeons. ResultsA significant trend toward an increase in the registration incidence for hepatoblastoma was observed (p<0.001). Hepatoblastomas with low birth weight (<1500g) represented as many as 16% of hepatoblastomas. In hepatocellular carcinoma, there was a significant trend toward a decrease (p=0.042). The registration incidence of nonmass screening-detected neuroblastoma remained unchanged until 2003, but the registration incidence in the period from 2004 to 2012 was significantly higher than that in the period from 1996 to 2003 (p=0.021). There was an increase in the relative incidence of favorable stages after the cessation of mass screening. ConclusionsThe notable increase in hepatoblastoma during the last three decades is partly attributed to an increase in hepatoblastoma in children of low birth weight, but this alone is not sufficient to explain the increase in hepatoblastoma. The increase in neuroblastoma after the halt of mass screening is so minimal that it is not recommended to consider reimplementation of mass screening.

Application of nuclear medicine to achieve less invasive surgery for malignant solid tumors in children.

The use of nuclear medicine for the management of malignant tumor, such as radioguided surgery and sentinel lymph node biopsy (SLNB), has been widely accepted in the adult practice. However, there are very few studies to apply those techniques for pediatric diseases. The aim of this study was to investigate the feasibility of application of nuclear medicine in surgery for neuroblastoma (NB) or rhabdomyosarcoma (RMS) in children. Radioguided surgery using (123) I-metaiodobenzylguanidine was performed on six children with NB. SLNB using technetium-labeled tin or sulfur colloid was performed on two children with perineal RMS. Histological evaluation of resected specimens was performed to determine the accuracy of intraoperative detection and SLNB. All patients were evaluated for overall survival and complications. Intraoperative tumor localization using hand-held gamma probe was helpful in 85.7% of NB patients. Sensitivity and specificity of this technique were 81.8% and 93.3%, respectively. There were no postoperative complications, and four out of five patients with high-risk NB experienced disease-free survival (median follow up, 57 months). Sentinel lymph nodes were easily detected in patients with perineal RMS, and histological assessment revealed complete consistency with regional lymph node status. Nuclear medicine may have a potential application in the use of less invasive surgery for advanced NB or perineal RMS, the two most challenging pediatric malignancies.

Rhabdomyosarcoma in adolescent and young adult patients: current perspectives.

Rhabdomyosarcoma (RMS), a malignant tumor of mesenchymal origin, is the third most common extracranial malignant solid tumor in children and adolescents. However, in adults, RMS represents <1% of all solid tumor malignancies. The embryonal and alveolar histologic variants are more commonly seen in pediatric patients, while the pleomorphic variant is rare in children and seen more often in adults. Advances in the research of the embryonal and alveolar variants have improved our understanding of certain genes and biologic pathways that are involved in RMS, but much less is known for the other variants. Multimodality therapy that includes surgery and chemotherapy with or without radiation therapy is the mainstay of treatment for RMS. Improvements in the risk stratification of the pediatric patients based on presurgical (primary tumor site, tumor size, regional lymph node involvement, presence of metastasis) and postsurgical parameters (completeness of resection or presence of residual disease or metastasis) has allowed for the treatment assignment of patients in different studies and therapeutic trials, leading to increases in 5-year survival from 25%–70% over the past 40 years. However, for adult patients, in great part due to rarity of the disease and the lack of consensus on optimal treatment, clinical outcome is still poor. Many factors have been implicated for the differing outcomes between pediatric RMS versus adult RMS, such as the lack of standardized treatment protocols for adult RMS patients and the increased prevalence of advanced presentations. Now that there are increased numbers of survivors, we can appreciate the sequelae from therapy in these patients, such as bone growth abnormalities, endocrinopathies, and infertility. Improvements in risk stratification have led to clinical trials using lower doses of chemotherapy or radiation therapy with the intention of decreasing the incidence of side effects without compromising survival outcome.

Dynamic MRI Findings and Clinical Features of Benign Hypervascular Hepatic Nodules in Childhood-Cancer Survivors

The purpose of this study is to investigate the dynamic MRI findings and clinical features of benign hypervascular hepatic nodules in childhood-cancer survivors. We reviewed dynamic MRI findings and clinical features in 15 patients who had been treated for childhood malignant solid tumors and in whom hypervascular hepatic nodules were later found on surveillance imaging by either CT or ultrasound (or both). The benign nature of the lesion was based on histologic examination or clinical and radiologic follow-up (or both). Time between initial diagnosis of malignancy and detection of the hepatic nodule ranged from 4.5 to 13.5 years with the majority of the malignancies being neuroblastoma treated by high-dose chemotherapy and hematopoietic stem cell transplantation. A total of 43 nodules were detected, often multiple and small. Most of the lesions were isointense or slightly hyperintense on T2-weighted imaging and isointense or slightly hypointense on T1-weighted imaging. All nodules had intense enhancement on the arterial phase and were isointense or slightly hyperintense on the delayed phase. A central scar was seen in four. Additionally, hepatic hemosiderosis was noted in four patients, in whom all the lesions were hyperintense on both T1- and T2-weighted imaging. Benign hypervascular hepatic nodules in survivors of childhood malignancy occur years after high-dose chemotherapy and hematopoietic stem cell transplantation. Dynamic MRI findings including intense arterial enhancement and absence of washout in the delayed phase are of great value in the differential diagnosis of these hepatic nodules.

Educational Achievement, Employment, Smoking, Marital, and Insurance Statuses in Long-term Survivors of Childhood Malignant Solid Tumors

Survivors of childhood cancer experience many social adaptation problems. We aimed to identify social, educational, and occupational issues of this growing population. Survivors treated for childhood malignant solid tumors who were older than 18 years and in remission for at least 3 years were surveyed. The educational achievement, employment, type of habitation, marital status, parenthood, social insurance, and smoking status of the patients were inquired and recorded. Two hundred one patients (126 male patients/75 female patients) were included in the study between 2007 and 2009. The median ages at the time of diagnosis and at the time of study were 10 years (range, 0 to 19 y) and 23 years (range, 18 to 39 y), respectively. The median follow-up duration was 13.5 years (range, 3 to 31 y). Nearly half of the participants were lymphoma survivors. One hundred eleven (55.5%) survivors were high school graduates and 47 (23%) were university graduates. Unemployment rate was 36.8%. Public social insurance rate was 90.5%. Fifty-three (26.4%) survivors had independent habitation. Thirty percent of survivors were married and 7.5% had at least 1 child. Marriage rates were significantly higher in survivors who were older than 23 years, had a follow-up duration of >13 years, had a job, and lived independently (for each parameter P=0.001). University degree was significantly lower in survivors who were treated for central nervous system tumors. Our results have drawn a more marked picture with lower educational achievement and marital rates when compared with the results of large survivorship studies conducted in developed countries. However, they can be interpreted as intriguing when limited resources are taken into account.

Rare coexistence of metastatic neuroblastoma of liver and solid pseudo papillary tumor of pancreas: Case report and literature review

Neuroblastoma is the second most common malignant solid tumor in children, and often metastasizes to liver, most notably in patients with stage 4S tumors. Solid pseudopapillary tumor of the pancreas (SPT) is a pancreatic borderline tumor with low malignant potential. Coexistence of these two tumors in one patient has never been reported before. Hereby, we present a case of an 8-month-old infant with coexisting tumors of SPT and metastatic neuroblastoma of liver. Dysdifferentiation of neural crest might be responsible for histogenesis of the coexisting tumors.

Spindle cell rhabdomyosarcoma displaying cd34 positivity: a potential diagnostic pitfall; report of two pediatric cases

Spindle cell rhabdomyosarcoma is a rare subtype of rhabdomyosarcoma mainly seen in children. Occasional aberrant staining with a variety of immunohistochemical markers has been noted. The aberrantly expressed markers include alpha-smooth muscle actin, cytokeratin, S100, neurofilaments, CD20, immunoglobins, and CD117. We report herein two pediatric cases displaying strong CD34 positivity and one with additional focal CD117 positivity, causing considerable difficulty in distinction from solitary fibrous tumor and extra-gastrointestinal stromal tumor. To our knowledge, CD34 staining has been merely reported in rhabdomyosarcoma. Spindle cell rhabdomyosarcoma has to be considered in the differential diagnosis of childhood spindle cell tumors. Post-chemotherapy specimens should be evaluated in caution, since chemotherapy can cause considerable changes in tumor antigen expression. Since CD117 and CD34 are stem cell markers, their positivity in pediatric tumors should be interpreted with caution. Even if the morphology is not supportive, a wide immunohistochemical panel should be applied in childhood malignant solid tumors.

MYCN gene monitoring in children's malignant solid tumors

Although the incidence of malignant solid tumors in children is not high,it is one of the major death causes in children.MYCN gene amplification is an independent poor prognosis factor of neuroblastoma.MYCN gene involves in neuroblastoma tumorgenesis and is the major evidence of treatment.MYCN gene amplification could be detected in other children's solid tumor.It is associated with unfavorable medulloblastoma pathology,poor outcome of Wilms' tumor and alveolar rhabdomyosarcomas.This review compares different MYCN gene detection methods,makes a summary about the clinical relationship between MYCN gene and children's solid tumor and investigates the possibility of increasing cure rate of malignant solid tumors through molecular specificity treatment. Key words: MYCN gene; Solid tumors; Neuroblastoma

Impact of N-myc Amplification on Median Survival in Children With Neuroblastoma

Background: Neuroblastoma is the most common extracranial malignant solid tumor in children under 5 years, and it is characterized by wide clinical and biological heterogeneity. N-myc oncogene amplification is considered to be one of the most important prognostic factors used to evaluate survival in these patients. Objectives: The aim of our study was to determine amplification of the N-myc oncogene using real-time quantitative polymerase chain reaction (PCR) and to show the influence of N-myc amplified tumors on the overall survival rate. Patients and Methods: This study is an analytical historical cohort study of forty children with neuroblastoma admitted to the Shafa Hospital, Iran from 1999 to 2010. Paraffined blocks of tumoral tissue were analyzed for N-myc amplification by a PCR. The degree of N-myc amplification was derived from the ratio of the N-myc oncogene and the single copy reference gene, NAGK. In the statistical analysis, a Kaplan-Meier survival analysis was used. Results: We found a variable degree of N-myc amplification, from 3 to 2 200, in 32 of the 40 neuroblastomas (80%). NMYC amplification was seen more frequently in patients older than 2.5 years (71.9%), stage 4 (65.6%) and female (53.1%). Median survival time in the males was significantly longer than in the females (P = 0.03). The overall median survival for N-myc amplified tumor patients was 20 months, and 30 months for the non amplified tumors. Conclusions: The N-myc amplified tumors may increase the probability of more aggressive behavior and rapid tumor progression, especially in advanced stages of neuroblastoma. This study confirmed the importance of obtaining correct measurements of oncogene amplification in the early evaluation of neuroblastomas in order to target more aggressive therapies in patients with a higher risk of cancer progression.

Impact of N-myc Amplification on Median Survival in Children With Neuroblastoma

Background: Neuroblastoma is the most common extracranial malignant solid tumor in children under 5 years, and it is characterized by wide clinical and biological heterogeneity. N-myc oncogene amplification is considered to be one of the most important prognostic factors used to evaluate survival in these patients. Objectives: The aim of our study was to determine amplification of the N-myc oncogene using real-time quantitative polymerase chain reaction (PCR) and to show the influence of N-myc amplified tumors on the overall survival rate. Patients and Methods: This study is an analytical historical cohort study of forty children with neuroblastoma admitted to the Shafa Hospital, Iran from 1999 to 2010. Paraffined blocks of tumoral tissue were analyzed for N-myc amplification by a PCR. The degree of N-myc amplification was derived from the ratio of the N-myc oncogene and the single copy reference gene, NAGK. In the statistical analysis, a Kaplan-Meier survival analysis was used. Results: We found a variable degree of N-myc amplification, from 3 to 2 200, in 32 of the 40 neuroblastomas (80%). NMYC amplification was seen more frequently in patients older than 2.5 years (71.9%), stage 4 (65.6%) and female (53.1%). Median survival time in the males was significantly longer than in the females (P = 0.03). The overall median survival for N-myc amplified tumor patients was 20 months, and 30 months for the non amplified tumors. Conclusions: The N-myc amplified tumors may increase the probability of more aggressive behavior and rapid tumor progression, especially in advanced stages of neuroblastoma. This study confirmed the importance of obtaining correct measurements of oncogene amplification in the early evaluation of neuroblastomas in order to target more aggressive therapies in patients with a higher risk of cancer progression.

The role of neoadjuvant chemotherapy in children with malignant solid tumors

Pediatric surgeons play a critical role in diagnosing, staging, and treating malignant solid tumors in children. Over the years, the surgical management of the primary tumor site has evolved from an aggressive en-bloc resection at diagnosis to a more tailored surgical approach, often affecting definitive local control after the delivery of neoadjuvant therapy, as currently directed by many solid tumor protocols. In fact, inappropriate upfront resection can lead to unnecessary short- and long-term morbidity, an incomplete resection, and may be associated with a delay in the initiation of the systemic chemotherapy that is critical to the treatment of gross or occult metastatic disease. Therefore, it is important for the pediatric surgeon, as a member of the multidisciplinary team involved in the care of these children, to understand the indications for and implications of neoadjuvant therapy in the treatment of pediatric solid tumors. Here we review the current management of childhood solid tumors focusing on the role of neoadjuvant therapy.