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Complement-mediated hemolytic uremic syndrome (CM-HUS) following chemotherapy for pediatric acute lymphoid neoplasms has rarely been reported. We report the case of an 8-year-old boy with T-lymphoblastic lymphoma (T-LBL) who developed CM-HUS with complement factor H (CFH) mutations (S1191L, V1197A) during induction therapy. Safe administration of chemotherapy after CM-HUS recovery was challenging. By closely monitoring hemolytic and renal parameters during the 2-year treatment period, we observed four episodes of microangiopathic hemolytic anemia (MAHA) with hypocomplementemia and low haptoglobin but no renal dysfunction or thrombocytopenia. Here, we describe the MAHA and CM-HUS episodes in the hopes of elucidating the complex pathophysiology of disorders associated with CFH mutation.

Primary malignant mediastinal germ cell tumors (GCTs) are rare pediatric tumors that have a poorer prognosis compared to GCTs occurring elsewhere in the body. The current study aimed to assess the prognostic factors and treatment outcomes of children with primary malignant mediastinal GCT in Taiwan.The authors retrospectively reviewed children 0-18 years old who were newly diagnosed with primary malignant mediastinal GCT between January 1, 2005 and December 31, 2019 and were registered in the Taiwan Pediatric Oncology Group patient registry. The impact of presenting characteristics, including sex, age, tumor stage, histology subtype, surgical treatment, and chemotherapy regimens of the patients were analyzed.This study enrolled 52 children with malignant mediastinal GCT who had a median age of 16.0 (range, 6.0-17.9) years at diagnosis. The most common histological subtypes were mixed GCTs (n = 20) and yolk sac tumors (n = 15). Advanced disease stage and choriocarcinoma histology subtype were associated inferior outcomes. Children who received surgical treatment exhibited better outcomes compared to those who did not (5-year overall survival, 78% vs. 7%, p .001). After comparing patients who received first-line cisplatin- and carboplatin-based chemotherapy, no difference in treatment outcomes was observed. Multivariate analysis showed that surgical management was the only independent predictor for superior OS.Surgical treatment is recommended for mediastinal GCT. Cisplatin-based chemotherapy was not superior to carboplatin-based chemotherapy as first-line treatment and may be avoided due to toxicity concerns.

This study aimed to describe and compare the differences in walking performance between adolescent patients in inpatient wards and outpatient units, and to identify factors that influence walking performance among adolescents receiving cancer treatment. The cross-sectional study with correlational research design recruited 32 adolescents with cancer between February 2015 and March 2017 in two teaching hospitals in Taiwan. Descriptive, bivariate, and multivariate regression analyses were used. Participants’ age, treatment setting, and symptom distress were significantly associated with number of walking steps. All independent variables in the model together accounted for 82.1% of variance. This study addresses a gap in the existing literature to identify associated factors that affected walking performance among adolescents undergoing cancer treatment. Our findings represent a pathway toward generating knowledge to enhance well-being for this unique population.

Silver nanoparticles (AgNPs) are increasingly used in our daily life and have become a potential environmental hazard. However, the toxic effects of AgNPs on the early stages of fish are not fully understood, and little is known about their effects on specific types of ionocytes. Using zebrafish embryos as a model, this study examined the effects (changes in cell number, morphology, NH4+ secretion and gene expression) of sublethal concentrations of AgNPs (0.1, 1, and 3 mg/L) on two major types of ionocytes: H+ pump-rich (HR) ionocytes, and Na+ pump-rich (NaR) ionocytes in the skin of embryos. After exposure to AgNPs for 96 h, the number of HR ionocytes significantly declined by 30% and 41% in the 1 and 3 mg/L AgNP groups, respectively. In addition, the apical opening of HR ionocytes became smaller, suggesting that AgNPs impaired the critical structure for ion transport. NH4+ secretion by HR ionocytes of embryos also declined significantly after AgNP exposure. In contrast, the number of NaR ionocytes increased by 29% and 43% in the 1 and 3 mg/L AgNP groups, respectively, while these cells deformed their shape. AgNPs altered mRNA levels of several ion channel and transporter genes involved in the functions of HR ionocytes and NaR ionocytes, and influenced hormone genes involved in regulating calcium homeostasis. This study shows that AgNPs can cause differential adverse effects on two types of ionocytes and the effects can threaten fish survival.

Background Parosteal osteosarcoma (POS) is a unique low grade osteosarcoma. Two separate oncogenes, MDM2 and CDK4, are specifically amplified in POS. Its clinical behavior is usually indolent. In some occasions, it may progress to high grade and become fatal. Malignant transformation with high grade differentiation is the most reliable indicator to predict its aggressiveness and metastatic potential. This study is to discover the relationship between gene amplification and grading. Methods Retrospective analysis of MDM2/CDK4 expression/amplification using immunostaining, multiplex quantitative polymerase chain reaction (MQPCR) and fluorescence in situ hybridization (FISH) were studied on 14 patients with recurrent POS. Results Forty tumor specimens in formalin-fixed paraffin-embedded blocks from 14 patients of POS were included in this study. Twenty-seven tumors are low-grade, 13 are high-grade. All POS showed increased expression of both MDM2 and CDK4 proteins, but not those from conventional osteosarcoma. Except some tumors were non-informative (poor DNA quality), the rest of POS had a marked increase of MDM2 and CDK4 genes copies by MQPCR, and confirmed by MDM2 FISH. Moreover, the folds of amplification increase as tumors progress. And, the amplification folds in high-grade POS are consistently higher than those of conventional ones. Conclusion FISH and MQPCR are both useful assays for estimating oncogene amplification status in bone tumors. Amplification levels of MDM2 and CDK4 are related to tumor grading and progression. Molecular determination of gene amplification status can be a reliable alternative for predicting clinical behavior of POS at small biopsies.

Background Asian studies on soft tissue sarcoma (STS) incidence, irrespective of the primary site, are scant. Methods STS data were acquired from the population-based 2007–2013 Taiwan Cancer Registry of the Health and Welfare Data Science Center, Taiwan. Histological subtype-, site-, sex-, and age-specific STS incidence rates were analyzed according to the 2013 classification of the World Health Organization. Results In total, 11,393 patients with an age-standardized incidence rate (ASIR) of 5.62 (95% confidence interval, 5.51–5.73) per 100,000 person-years were identified. Overall, a male predominance (sex-standardized incidence rate ratio, 1.2) was noted, and the rate increased with age, peaking at >75 years. Approximately 30% of STSs occurred in connective, subcutaneous, and other soft tissues and 70% in other sites. In addition to connective, subcutaneous, and other soft tissues, the three most common primary sites were the stomach (15.9%), skin (14.3%), and small intestines (10.5%). Gastrointestinal stromal tumor was the most common subtype (29.2%; ASIR, 1.55/100,000 person-years), followed by liposarcoma (11.5%; ASIR, 0.63/100,000 person-years) and leiomyosarcoma (9.7%; ASIR, 0.53/100,000 person-years). Compared with relevant data from Western countries, the incidence rate of angiosarcomas was higher than that in other regions, whereas the incidence rates of leiomyosarcoma and Kaposi sarcoma were lower than those in other regions. Conclusion STS incidence varied by histological subtype, sex, age, and primary site in an Asian population. Our results suggested regional and racial discrepancies in the incidence rates of certain STS subtypes.

BACKGROUND Despite aggressive treatment including surgery, radiotherapy, and adjuvant chemotherapy, the outcome of pediatric high-risk embryonal brain tumors remains poor; especially in young children, in whom early radiotherapy inevitably brings significant long-term morbidities. Single or tandem autologous stem cell transplant has been reported to improve outcomes; but optimal use is not well defined. METHODS Pediatric patients with high-risk embryonal brain tumors who underwent tandem transplant as consolidation from August 2011 to December 2017 were included. We performed a retrospective chart review and analyzed the outcomes to identify possible prognostic factors. RESULTS Eleven pediatric patients with high-risk embryonal brain tumors were enrolled. They received double or triple autologous transplant at complete response in 5 patients and at partial response in 6 for a total of 24 transplants. There were five atypical teratoid rhabdoid tumors, four medulloblastoma, one primitive neuroectodermal tumors, and one pineoblastoma. Median age at diagnosis was 1.8 years (range, 0.6-11.2 years) and at transplant was 2.2 years (range, 1.2-11.9 years). Thiotepa-based regimens were used in 13 cycles of conditioning. All patients achieved successful engraftment. No transplant-related mortality was identified. With a median follow-up of 21.2 months (range, 6.9-51.8 months), seven patients had disease progression. Disease entity and the use of one or more cycles of thiotepa-based regimen during tandem transplant had statistically significant impact on both progression-free survival and overall survival. CONCLUSION With successful engraftment and manageable toxicity, tandem transplant in pediatric patients with high-risk embryonal brain tumor is feasible and safe. Patients receiving tandem transplant with one or more cycles of thiotepa-based regimen might have better outcome than those without. In combination with salvage radiotherapy, a favorable 2-year overall survival could be achieved in the majority of patients.

Pharmaceuticals and personal care products are emerging environmental pollutants. Cisplatin, one of the most widely used platinum-based chemotherapeutic agents, has been found to contaminate aquatic environments. Using zebrafish embryos as a model, cisplatin was previously found to impair skin ionocytes and ion regulation. The purpose of this study was to further investigate how cisplatin damages ionocytes. Zebrafish embryos were exposed to cisplatin (0, 50, and 100 μM) for 96 h (4-100 h post-fertilization) and then stained with fluorescent dyes to reveal mitochondrial activity (rhodamine123), apoptosis (acridine orange), and oxidative stress (CellROX/MitoSOX) in ionocytes of living embryos. Results showed that cisplatin exposure decreased rhodamine 123-labeled ionocytes, induced oxidative stress in ionocytes, and promoted apoptosis in a concentration-dependent manner. Quantitative PCR analysis showed that mRNA levels of antioxidative genes (sod1, sod2, gpx1a, and cat) and an apoptotic gene (caps3a) were induced. In the time-course experiment at 96-98 h post-fertilization, cisplatin increased oxidative stress and apoptosis in ionocytes in a time-dependent manner. In conclusion, this study demonstrates that cisplatin exposure induces oxidative stress, mitochondrial damage, and apoptosis in ionocytes of zebrafish embryos.

Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0–18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996–December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008–2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996–2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1–RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008–2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008–2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008–2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents’ use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.

We herein report the case of a girl with PRETEXT III hepatoblastoma (HB) developing recurrent lung metastases despite multiple chemotherapy regimens, aggressive tumor excision, multiple lung metastasectomies, and autologous peripheral blood stem cell transplantation. High tumor mutation burden (TMB) was identified through targeted next-generation sequencing, and pembrolizumab was administered post-operatively as a last resort. A complete and sustained response to the immune checkpoint inhibitor was achieved for 22 months. Although the majority of HB have a low TMB, immune checkpoint inhibitor therapy may be useful for patients with refractory HBs with a high TMB.

Synovial sarcoma is a rare but aggressive soft-tissue sarcoma associated with translocation t(X, 18). Metastasis occurs in approximately 50% of all patients, and curative outcomes are difficult to achieve in this group. Since the efficacies of current therapeutic approaches for metastatic synovial sarcoma remain limited, new therapeutic agents are urgently needed. Tilapia piscidin 4 (TP4), a marine antimicrobial peptide, is known to exhibit multiple biological functions, including anti-bacterial, wound-healing, immunomodulatory, and anticancer activities. In the present study, we assessed the anticancer activity of TP4 in human synovial sarcoma cells and determined the underlying mechanisms. We first demonstrated that TP4 can induce necrotic cell death in human synovial sarcoma AsKa-SS and SW982 cells lines. In addition, we saw that TP4 initiates reactive oxygen species (ROS) production and downregulates antioxidant proteins, such as uncoupling protein-2, superoxide dismutase (SOD)-1, and SOD-2. Moreover, TP4-induced mitochondrial hyperpolarization is followed by elevation of mitochondrial ROS. Calcium overload is also triggered by TP4, and cell death can be attenuated by a necrosis inhibitor, ROS scavenger or calcium chelator. In our experiments, TP4 displayed strong anticancer activity in human synovial sarcoma cells by disrupting oxidative status, promoting mitochondrial hyperpolarization and causing calcium overload.

Objective To provide strategies for monitoring and treating severe lung involvement in Gaucher disease. Study design We reviewed the chart of a 5-year-old boy who developed rapidly progressive, severe infiltrative lung involvement of Gaucher disease (GD) and improved after allogeneic hematopoietic stem cell transplant (HSCT), along with other case studies reported before December 2019. He was diagnosed with GD (homozygous mutation at c.1448 T > C, p.L483P), and started receiving enzyme replacement therapy (ERT) at 17 months old. He developed respiratory distress symptoms after 45 months of ERT; chest imaging reported diffuse interstitial infiltration of the bilateral lungs and consolidations at the right lungs. Allogeneic HSCT using cells from a matched unrelated donor was performed four months upon progressive respiratory symptoms. Results His respiratory symptoms subsided in one month; chest imaging improvement, pulmonary function test improvement, and normalized activity of β-glucocerebrosidase were reported in three months. Conclusion This is the first report of a patient who received early and regular ERT but developed severe infiltrative lung involvement and recovered after allogeneic HSCT. Based on study results, we suggest regular chest imaging, even for asymptomatic patients. For patients with severe lung involvement, rapid deterioration, and unresponsive to higher ERT dosages, allogeneic HSCT should be considered.

Background Patients with childhood cancer are at increased risk for the development of second cancers. Methods A national multicenter survey of second cancers conducted by the Taiwan Pediatric Oncology Group retrieved retrospective data from the database at the Children Cancer Foundation in Taiwan beginning in 1995. The characteristics of second cancers and associations of patient demographic and clinical characteristics with time to death due to a second cancer were analyzed. Results We examined the records of 8782 patients with a primary cancer diagnosed between January 1, 1995 and December 31, 2013, and a total of 99 patients with a second cancer were identified. The most common type of second cancer was acute myeloid leukemia (n = 35), followed by acute lymphoblastic leukemia (n = 15), central nervous system (CNS) tumors (n = 15), and sarcomas (n = 10). Secondary hematological malignancies occurred earlier than other secondary cancers. The frequencies of second CNS tumors and second bone cancers and sarcomas were notably increased when prior radiation doses increased from zero, low dose to high dose. The overall 5-year survival of patients with a second cancer was poor (33.7%). Multivariate survival analysis revealed that the year of primary diagnosis ≤2002, secondary hematological malignancies, and age at second cancer diagnosis ≤9.3 years or >26.8 years increased the risk of death following second cancer. Conclusion Children who develop a second cancer have an unfavorable outcome. Early detection and improved treatment for second cancers are needed.

Ammonia (including NH3 and NH4+) is a major pollutant of freshwater environments. However, the toxic effects of ammonia on the early stages of fish are not fully understood, and little is known about the effects on the sensory system. In this study, we hypothesized that ammonia exposure can cause adverse effects on embryonic development and impair the lateral line system of fish. Zebrafish embryos were exposed to high-ammonia water (10, 15, 20, 25, and 30 mM NH4Cl; pH 7.0) for 96 h (0–96 h post-fertilization). The body length, heart rate, and otic vesicle size had significantly decreased with ≥15 mM NH4Cl, while the number and function of lateral-line hair cells had decreased with ≥10 mM NH4Cl. The mechanoelectrical transduction (MET) channel-mediated Ca2+ influx was measured with a scanning ion-selective microelectrode technique to reveal the function of hair cells. We found that NH4+ (≥5 mM NH4Cl) entered hair cells and suppressed the Ca2+ influx of hair cells. Neomycin and La3+ (MET channel blockers) suppressed NH4+ influx, suggesting that NH4+ enters hair cells via MET channels in hair bundles. In conclusion, this study showed that ammonia exposure (≥10 mM NH4Cl) can cause adverse effects in zebrafish embryos, and lateral-line hair cells are sensitive to ammonia exposure.

Background The incidence of immune thrombocytopenia (ITP) is not well known in Asians. The aims of this study were to survey incidences and clinical features of ITP in Taiwan. Study design and methods This study identified 4855 incident ITP cases from the population-based National Health Insurance Research Database from mid-2006 to mid-2013, and compared incidences, patient characteristics, and clinical manifestations of ITP by age. Results Respective ITP incidence rates among those aged 15 years. Conclusion Incidence estimates of ITP in Taiwan were close to those of Western countries, with age-specific variations in sex ratio, comorbidity, splenectomy, secondary causes, and incidence trends. The results suggest no racial variations in ITP incidences, but a geographical difference in causes of secondary ITP.

Cancer during adolescence increases the risk for bone mass deficiency later in life. Adolescents with cancer must learn to improve their bone health to avoid osteoporosis. In the present cross-sectional study, we developed and tested scales to assess the bone health self-efficacy and beliefs of adolescents with cancer in Taiwan. Test development followed three stages: item generation and scale formatting, examination of content validity, and validation of psychometric properties with a sample of 100 adolescents with cancer. Through the validation process, this research generated the seven-item Bone Health Self-Efficacy Scale and the 13-item Bone Health Belief Scale. Multiple indices demonstrated construct validity. Cronbach's alphas (0.809 and 0.705) demonstrated internal consistency. No items caused a drop in Cronbach's alpha of 10%, all inter-item correlations were

Acidification of freshwater ecosystems is recognized as a global environmental problem. However, the influence of acidic water on the early stages of freshwater fish is still unclear. This study focused on the sublethal effects of acidic water on the lateral line system of zebrafish embryos. Zebrafish embryos were exposed to water at different pH values (pH 4, 5, 7, 9, and 10) for 96 (0–96 h post-fertilization (hpf)) and 48 h (48∼96 hpf). The survival rate, body length, and heart rate significantly decreased in pH 4-exposed embryos during the 96-h incubation. The number of lateral-line neuromasts and the size of otic vesicles/otoliths also decreased in pH 4-exposed embryos subjected to 96- and 48-h incubations. The number of neuromasts decreased in pH 5-exposed embryos during the 96-h incubation. Alkaline water (pH 9 and 10) did not influence embryonic development but suppressed the hatching process. The mechanotransducer channel-mediated Ca2+ influx was measured to reveal the function of lateral line hair cells. The Ca2+ influx of hair cells decreased in pH 5-exposed embryos subjected to the 48-h incubation, and both the number and Ca2+ influx of hair cells had decreased in pH 5-exposed embryos after 96 h of incubation. In addition, the number and function of hair cells were suppressed in H+-ATPase- or GCM2-knockdown embryos, which partially lost the ability to secrete acid into the ambient water. In conclusion, this study suggests that lateral line hair cells are sensitive to an acidic environment, and freshwater acidification could be a threat to the early stages of fishes.

BACKGROUND Enumerating hematopoietic progenitor cells (HPCs) by using an automated hematology analyzer is a rapid, inexpensive, and simple method for predicting a successful harvest compared with enumerating circulating CD34+ cells. However, the optimal HPC cutoff count and the indicating factors to be considered for improved predicting have not yet been determined. STUDY DESIGN AND METHODS Between 2007 and 2012, a total of 189 consecutive patients who proceeded to peripheral blood stem cell (PBSC) harvesting were retrospectively recruited. Baseline characteristics were analyzed to identify the risk factors for a failed harvest, which were defined as less than 2 × 106 CD34+ cells/kg. Variables identified by multivariate logistic regression and correlation analysis for predicting a successful harvest were subjected to classification and regression tree (CART) analysis. RESULTS PBSCs were successfully harvested in 154 (81.5%) patients. An age of at least 60 years, a diagnosis of a solid tumor, at least five prior chemotherapy cycles, prior radiotherapy, and mobilization with granulocyte–colony-stimulating factor alone or high-dose cyclophosphamide were independent baseline predictors of poor mobilization. In CART analysis, patients with zero to two host risk factors and either higher HPC (≥28 × 106/L) or mononuclear cell (MNC; ≥3.5 × 109/L) counts were categorized as good mobilizers and their harvest success rate was 92.3%. By contrast, 30.3% of harvests were adequate in the patients with three to five host risk factors and lower HPC and MNC counts. CONCLUSION A CART algorithm incorporating host predictors and HPC and MNC counts improves predictions in a successful harvest and might reduce the necessity of monitoring peripheral CD34+ cells.

Juvenile myelomonocytic leukemia (JMML) is a rare hematologic malignancy in children. Its presentations include anemia, thrombocytopenia, monocytosis, skin rash, marked hepatomegaly, and/or splenomegaly. Fever and respiratory involvement are common. Here, we report a case of a premature neonate with initial symptoms of respiratory distress. She gradually developed clinical manifestations of JMML that mimicked neonatal sepsis. Three weeks after birth, JMML was diagnosed. This is the first reported case of JMML presenting in a premature infant in Taiwan.

This study aimed to describe cancer incidence rates and trends specifically for adolescents aged 15-19 years during 1995-2009 in Taiwan. The incidence counts and census data were obtained from the population-based Taiwan Cancer Registry. During the 15-year study period, 4122 adolescents were diagnosed with cancer. The overall incidence rate was 155.2 per million person-years. Other epithelial tumors were the most frequently diagnosed cancer group (23.7%), followed by leukemias (18.0%) and lymphomas (13.9%). When compared to rates in Western countries, a significantly low rate of lymphomas was found. Moreover, rates of the subtypes of melanomas and nasopharyngeal carcinomas being 1/10- and 4-times rates in Western countries were the most striking variations. During 1995-2009, the overall rate of adolescent cancer did not significantly change. However, the most significant upward and declining trends in incidence rates were found for male germ cell neoplasms (annual percent change, APC, 6.4%) and hepatic tumors (APC, -11.1%), respectively. Further investigation and enhancement of the public discourse of possible lifestyle and environmental risk factors associated with increasing trends of certain adolescent cancers should be carried out in Taiwan.

Objective: This article reviews the current standard of care for osteosarcoma and the experience of Taipei Veterans General Hospital. Data Sources and Study Selection: We searched PubMed using the keyword “osteosarcoma” and article type “Clinical Trial.” Prospective, randomized, Phase II/III clinical trials which resulted in practice change were enrolled. In addition, retrospective studies from Taipei Veterans General Hospital were also included. Results: For localized conventional osteosarcoma, combined perioperative chemotherapy with surgical resection dramatically improved long-term outcomes. Combination chemotherapy with methotrexate, Adriamycin, and cisplatin (MAP) is currently widely accepted to be the optimal regimen. The efficacy of chemotherapy has increased the likelihood of a limb-salvage approach, which has become the mainstay of surgery. In Taipei Veterans General Hospital, MAP plus ifosfamide was used and could achieve a 5-year overall survival (OS) rate of 77% and progression-free survival (PFS) rate of 70% for all patients. For nonmetastatic osteosarcoma, the 5-year OS and PFS rates reached 90% and 83%, respectively. For recurrent/metastatic disease, there is currently no satisfactory systemic therapy. Removal of all tumors should be attempted if clinically feasible, because one-third of patients may survive for 5 years or more if the tumors are completely resected. Conclusion: Perioperative chemotherapy is associated with excellent OS, PFS, and limb salvage rates and is the current standard of care for osteosarcoma.

Environmental contamination by anticancer pharmaceuticals has been widely reported. These drugs are not readily biodegradable, and their parent compounds and/or metabolites have been detected in surface waters and groundwater throughout the world. Adverse effects of anticancer drugs occur frequently in cancer patients, and a large body of clinical knowledge has accumulated. However, the effects of these drugs on aquatic organisms have not been thoroughly studied. This study aimed to investigate the effects of acute exposure to a common anticancer drug, vincristine (VCR), on zebrafish embryonic development and skin function. After 96 h of VCR exposure (0, 1, 10, 15, and 25 mg/L), significant teratogenic effects were observed, including growth retardation, pericardial edema, spine, tail, and yolk sac malformations (VCR ≥ 15 mg/L), a decreased heart rate, and ocular malformations (VCR ≥ 10 mg/L). The value of the half lethal concentration for zebrafish embryos was 20.6 mg/L. At ≥10 mg/L VCR, systemic ion contents and acid secretion in the skin over the yolk-sac decreased, and these findings were associated with decreases in skin ionocytes (H+-ATPase-rich cells and Na+-K+-ATPase-rich cells). Also, the microridge-structure of skin keratinocytes was significantly damaged. The number of lateral line hair cells was reduced when VCR was ≥10 mg/L, and functional impairment was detected when VCR was as low as 1 mg/L. Results of this in vivo study in zebrafish embryos indicate that acute exposure to VCR can lead to developmental defects, impairment of skin functions, and even fish death.

The objective of this study was to examine whether physical activity self-efficacy mediated the adverse effect of symptom distress on exercise involvement among adolescents undergoing cancer treatment. A secondary data analysis approach was used to analyse a pooled sample of 97 adolescents who were undergoing cancer treatment in paediatric oncology/haematology wards and ambulatory settings in northern Taiwan. Mediation analysis was performed to examine the mediation relationship among physical activity self-efficacy, symptom distress and exercise involvement. The total effect (path c) (p < 0.001), the indirect effect (paths a and b) (p < 0.05 and p < 0.01) and the direct effect (path c') (p < 0.001) were significant. The bootstrapping test was significant (95% CI: -0.356 to -0.016), indicating that physical activity self-efficacy partially mediated the adverse effect of symptom distress on exercise involvement after adjusting for age, gender and cancer diagnosis. Physical activity self-efficacy partially mediates the relationship between symptom distress and exercise involvement for adolescents undergoing cancer treatment. There is an imperative need for healthcare professionals to design interventions to enhance these adolescents' physical activity self-efficacy, increase their exercise involvement and thus improve their quality of life.

This study aimed to assess the sublethal effects of a platinum-based compound, cisplatin, using a zebrafish model. Zebrafish embryos were incubated in different concentrations of cisplatin at 0–96 h post-fertilization. Using a non-invasive, scanning ion-selective electrode technique (SIET), we measured the functions of hair cells (Ca2+ influx) and ionocytes ([H+] gradients). The survival rate, hatching rate, phenotype, body length, whole-body ion (Na+, Cl−, and Ca2+) and Pt contents were also determined. The effects of cisplatin on zebrafish embryos were demonstrated as first impairing hair cell function (at 1 μM of cisplatin), the hair cell number, and body ion content of Cl− (at 10 μM of cisplatin), then decreasing ionocyte acid secretion and overall body ion contents of Na+ and Ca2+ (at 50 μM of cisplatin). The body length and ionocyte density decreased at 100 μM of cisplatin, and survival decreased at 500 μM of cisplatin. As the cisplatin concentration increased, the accumulation of Pt in fish embryos also increased. These results revealed that hair cells are significantly more susceptible to cisplatin toxicity than ionocytes. By determining the lowest observed effective concentration of cisplatin that caused in vivo functional alterations of zebrafish hair cells and skin ionocytes, this model demonstrated 500-fold greater sensitivity than by detecting changes in survival, for early assessment of the effects of platinum-based chemotherapeutic drugs on fish.

A 2-year-old Asian girl presented to our facility for the evaluation of thrombocytopenia. She was treated with intravenous immunoglobulin under the impression of immune thrombocytopenia. However, her body temperature spiked and progressive pancytopenia, hepatosplenomegaly, abnormal liver function, coagulopathy, and pulmonary infiltration developed. The final diagnosis was systemic Epstein-Barr virus (EBV)-positive T-cell lymphoma of childhood with hemophagocytic syndrome. This type of cancer is extremely rare but occurs more commonly in Asians. Its prognosis is generally poor, and a treatment strategy is yet to be established. Double staining for EBV-encoded RNA and CD3 or CD8 is crucial for diagnosis. This type of lymphoma must be diagnosed differentially from acute EBV-associated hemophagocytic lymphohistiocytosis, which is considered nonmalignant. This case report highlights the importance of awareness of this type of rare cancer, a comprehensive diagnostic approach, and close communication between primary care physicians and pathologists.

Background Discontinuation of E. coli l-asparaginase in patients with acute lymphoblastic leukemia (ALL) is unavoidable upon severe allergic reaction. We sought to examine outcomes following E. coli l-asparaginase discontinuation due to severe allergic reactions. Procedure We evaluated the outcome of children enrolled in Taiwan Pediatric Oncology Group-2002-ALL protocol between 2002 and 2012, who had E. coli l-asparaginase discontinued due to severe allergic reactions, and compared the outcomes of those who continued with Erwinia l-asparaginase (Erwinase) with those who did not. Results Among 700 patients enrolled in this study, 33 patients had E. coli l-asparaginase treatment discontinued due to severe allergic reactions. Five-year overall survival did not differ significantly among the 648 patients without discontinuation (81 ± 1.6%, mean ± SE), compared to 17 patients with allergic reactions and treated with Erwinase (88 ± 7.8%) and 16 patients with allergic reactions but not treated with Erwinase (87 ± 8.6%). Among 16 patients who did not receive Erwinase, all 10 who received ≥50% of the scheduled doses of E. coli l-asparaginase before discontinuation survived without events. Conclusions Erwinase treatment may not be needed for some ALL patients with severe allergy to E. coli l-asparaginase if ≥50% of prescribed doses were received and/or therapy is augmented with other agents.

Background & Aims This study examined and compared the incidence patterns of hepatocellular carcinoma among age groups in Taiwan, 30years after a universal hepatitis B virus immunization program was launched. Methods Data for hepatocellular carcinoma diagnosed in 2003–2011 were collected from the population-based Taiwan Cancer Registry. Age-standardized incidence rates were calculated to analyze and compare the changes in incidence rates and trends. More specific analyses were performed on four age groups separated by sex. Results A total of 82,856 patients were diagnosed with hepatocellular carcinoma in 2003–2011 in Taiwan, yielding an age-standardized incidence rate of 32.97 per 100,000 person-years. Hepatocellular carcinoma was predominantly diagnosed in middle-aged adults (50.1%) and elderly people (49.1%), in contrast to the low incidences in children (0.04%) and adolescents and young adults (0.8%). Striking variations in trends were found for children (annual percent change: −16.6%, 2003–2010) and adolescents and young adults (annual percent change: −7.9%, 2003–2011). The incidence rate of hepatocellular carcinoma in children decreased to zero in 2011; only a slight decline in trends occurred for the middle-aged group (annual percent change: −2%, 2003–2011), and a slight upward trend was observed for elderly people (1.3%), specifically in women (1.7%). Conclusions In Taiwan, hepatitis B virus-related hepatocellular carcinoma was nearly eradicated in children in 2011. The findings on age-specific incidence patterns and trends of hepatocellular carcinoma suggest that different control strategies for treating this devastating disease in the future be made according to age.

The incidence of immune thrombocytopenia (ITP) is not well known in Asians. The aims of this study were to survey incidences and clinical features of ITP in Taiwan.This study identified 4855 incident ITP cases from the population-based National Health Insurance Research Database from mid-2006 to mid-2013, and compared incidences, patient characteristics, and clinical manifestations of ITP by age.Respective ITP incidence rates among those aged15, 15 to 59, and ≥60 years were 4.0, 2.0, and 5.4 per 100,000 person-years. A male predominance was noted in children, and a female predominance was found in adults. The most common causes of secondary ITP were systemic lupus erythematosus (21.8%), viral hepatitis C (16.9%), and viral hepatitis B (13.4%). The rate of secondary ITP in children was less than one fifth that in adults (4.2% vs. 23.8%). Rates of central nervous system (1.1%) and gastrointestinal tract bleeding (3.3%) were rare, with variations by age. The rate of splenectomies in children (0.4%) was only one tenth that in adults (4.1%). The disease in 25% of children and 30% of adults became persistent or chronic. A decreasing trend in the ITP incidence was found (annual percentage change, -4.9%), and it was confined to those aged15 years.Incidence estimates of ITP in Taiwan were close to those of Western countries, with age-specific variations in sex ratio, comorbidity, splenectomy, secondary causes, and incidence trends. The results suggest no racial variations in ITP incidences, but a geographical difference in causes of secondary ITP.

Cancer during adolescence increases the risk for bone mass deficiency later in life. Adolescents with cancer must learn to improve their bone health to avoid osteoporosis. In the present cross-sectional study, we developed and tested scales to assess the bone health self-efficacy and beliefs of adolescents with cancer in Taiwan. Test development followed three stages: item generation and scale formatting, examination of content validity, and validation of psychometric properties with a sample of 100 adolescents with cancer. Through the validation process, this research generated the seven-item Bone Health Self-Efficacy Scale and the 13-item Bone Health Belief Scale. Multiple indices demonstrated construct validity. Cronbach's alphas (0.809 and 0.705) demonstrated internal consistency. No items caused a drop in Cronbach's alpha of 10%, all inter-item correlations were0.800, and the factor loadings for all items reached 0.400, demonstrating item appropriateness. The present study provides initial evidence of the scales' accessibility and feasibility for adolescents with cancer who speak Mandarin. These scales might also help clinical nurses evaluate the effectiveness of bone health education provided to adolescents with cancer.

BACKGROUND Currently, little information is available on childhood cancer incidence rates in Eastern Asia. The objective of this study was to report the first population-based cancer surveillance of children and adolescents in Taiwan. METHODS Data from the Taiwan Cancer Registry were examined for cancer frequencies and incidence rates among individuals ages birth to 19 years from 1995 to 2009. Types of cancers were grouped according to the International Classification of Childhood Cancer. Rates were compared by sex and age. For further comparisons with other countries, rates were age standardized to the 2000 world standard population in 5-year age groups. Trends in incidence rates also were evaluated. RESULTS In total, 12,315 individuals were diagnosed with childhood cancers, for an age-standardized incidence rate (ASR) of 132.1 per million person-years from 1995 to 2009. The male-to-female incidence rate ratio was 1.19. Overall, leukemias were the most common cancer (ASR, 39.1 per million person-years), followed by central nervous system neoplasms (15.8 per million person-years), and lymphomas (15.3 per million person-years). During the 15-year study period, the incidence rates increased by 1% annually. Compared with other countries, the rate of hepatic tumors was 2 times greater in Taiwan. The rate of germ cell neoplasms in Taiwan was similar to that in the United States and was 1.3 to 1.9 times greater compared with Canada, Brazil, Israel, and Japan. CONCLUSIONS Based on the current data, the observed increase in overall incidence rates was attributable only marginally to improvements in case ascertainment and diagnostic procedures. The high rates of malignant hepatic tumors and germ cell neoplasms in Taiwan suggest variations in the background risk factors. Cancer 2014;120:3545–3553. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. The authors examine cancer incidence patterns in children and adolescents based on a national, population-based cancer registry of 12,315 individuals in Taiwan from 1995 to 2009. The high rates of malignant hepatic tumors and germ cell neoplasms in Taiwan suggest variations in background risk factors.

Zebrafish lateral-line hair cells are an in vivo model for studying hair cell development, function, and ototoxicity. However, the molecular identification and properties of the mechanotransducer (MET) channel in hair cells are still controversial. In this study, a noninvasive electrophysiological method, the scanning ion-electrode technique (SIET), was applied for the first time to investigate properties of MET channels in intact zebrafish embryos. With the use of a Ca2+-selective microelectrode to deflect hair bundles and simultaneously record the Ca2+flux, the inward Ca2+flux was detected at stereocilia of hair cells in 2- to ∼4-day postfertilization embryos. Ca2+influx was blocked by MET channel blockers (BAPTA, La3+, Gd3+, and curare). In addition, 10 μM aminoglycoside antibiotics (neomycin and gentamicin) were found to effectively block Ca2+influx within 10 min. Elevating the external Ca2+level (0.2–2 mM) neutralized the effects of neomycin and gentamicin. However, elevating the Mg2+level up to 5 mM neutralized blockade by gentamicin but not by neomycin. This study demonstrated MET channel-mediated Ca2+entry at hair cells and showed that the SIET to be a sensitive approach for functionally assaying MET channels in zebrafish.

In childhood acute lymphoblastic leukemia (ALL), t(1;19)(q23;p13.3) with TCF3-PBX1 fusion is one of the most frequent translocations. Historically, it has been associated with poor prognosis. Intensive treatment, however, has improved its outcome. We determined the outcome of children with this genotype treated with contemporary intensive chemotherapy in Taiwan.In Taiwan Pediatric Oncology Group 2002 ALL studies, genotypes were determined by cytogenetic analysis and/or reverse transcriptase polymerase chain reaction assay. Based on presenting features, immunophenotype and genotype, patients were assigned to one of the three risk groups: standard risk (SR), high risk (HR), or very high risk (VHR). The patients with t(1;19)/TCF3-PBX1 were treated in the HR arm receiving more intensive chemotherapy. The outcomes of patients with t(1;19)/TCF3-PBX1 were compared to that of patients with other subtypes of B-precursor ALL (B-ALL).Of the 1,129 patients with B-ALL, 64 (5.7%) had t(1;19)/TCF3-PBX1; 51 of whom were treated in the HR arm, but 11 were treated in the VHR and 2 in the SR arm because of physician's preference. As a group, 64 patients with t(1;19)/TCF3-PBX1 had similar 5-year event-free survival (83.3 ± 4.8%) as those with TEL-AML1 (85.2 ± 3.4%, P = 0.984) or those with hyperdiploidy50 (84.0 ± 3.1%, P = 0.748). The cumulative risk of any (isolated plus combined) central nervous system relapse among patients with t(1;19)/TCF3-PBX1 (8.7 ± 3.8%) tended to be higher than that of patients with TEL-AML1 (5.8 ± 2.3%, P = 0.749) or those with hyperdiploidy (4.1 ± 1.8%, P = 0.135), albeit the differences did not reach statistical significance.With contemporary intensive chemotherapy, children with t(1;19)/TCF3-PBX1 fared as well as those with favorable genotypes (TEL-AML1 or hyperdiploidy).

To identify the prognostic factors and long-term outcome of the Ewing sarcoma family of tumors (ESFT), data on 50 patients with ESFT treated at Taipei Veterans General Hospital between February 1991 and March 2014 were retrospectively considered. The influence of patient demographics, tumor features, and clinical and therapeutic parameters on overall survival (OS) and progression-free survival (PFS) rates were assessed. The results revealed that 21 of the 50 patients (42%) were metastatic at diagnosis. The median follow-up time was 1.8 years. The 5-year OS and PFS for patients who were nonmetastatic were 61.6% and 55.5%, respectively, and 18.8% and 15.4% for patients who were metastatic, respectively. The key adverse prognostic factor was metastasis at diagnosis. Radiotherapy for local control was associated with improved PFS. The high rate of primary metastasis and poorer outcomes of nonmetastatic ESFT compared with results from Western studies, along with previously reported low rates of ESFT in Taiwanese people, suggest that genetic factors play a role in the pathogenesis of ESFT and chemotherapy pharmacokinetics and pharmacodynamics. Radiotherapy in local treatment should be considered more aggressively in Taiwanese patients with ESFT.

Background Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard-risk (SR, or “low-risk” in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy. Procedure From 2002 to 2012, all newly diagnosed children with ALL in Taiwan were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol. SR patients were randomized to receive single or double reinduction courses. The patients enrolled before 2009 received CrRT, while those enrolled later did not. The Kaplan–Meier method was used to estimate survival rates and the difference between two groups was compared by the two-sided log-rank test. Results In 1,366 eligible patients, the 5-year overall survival (OS) was 81.6 ± 1.1% (standard error) and 5-year event-free survival (EFS) was 74.3 ± 1.2%. In SR patients, the 5-year OS for one and two reinduction courses was 91.6 ± 2.1% and 93.7 ± 1.8%, respectively, and the 5-year EFS was 85.2 ± 2.7% and 89.8 ± 2.3%, respectively. There were no significant differences in survival between these two groups. Patients with MLL or BCR-ABL1 had the worst outcomes: 5-year EFS was 23.4 and 31.8% and 5-year OS was 28.6 and 44.7%, respectively. There was no significant difference in CNS relapse or survival between the era with or without CrRT. Conclusions For SR patients, one-course reinduction was adequate. Triple intrathecal therapy alone successfully prevented CNS relapse.