Giun Yi Hung

Long-term results of Taiwan Pediatric Oncology Group studies 1997 and 2002 for childhood acute lymphoblastic leukemia

The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between 1997 and 2007, is reported. The event-free survival improved significantly (P=0.0004) over this period, 69.3±1.9% in 1997–2001 to 77.4±1.7% in 2002–2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997–2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy >50 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy >50, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.

Cancer incidence patterns among children and adolescents in Taiwan from 1995 to 2009: A population-based study

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.

Changing incidence patterns of hepatocellular carcinoma among age groups in Taiwan

BACKGROUND & AIMS This study examined and compared the incidence patterns of hepatocellular carcinoma among age groups in Taiwan, 30 years 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.

Geographic Variation in Cancer Incidence among Children and Adolescents in Taiwan (1995–2009)

Background Evidence from our recent study suggested that the overall trend for cancer incidence in children and adolescents has been increasing in Taiwan. Methods To analyze geographic variations in this trend, cancer frequencies and incidence rates of disease groups were quantified according to geographic areas among 12,633 patients aged <20 years during 1995–2009 by using the population-based Taiwan Cancer Registry. Three geographic levels were defined, namely county or city, region (Northern, Central, Southern, and Eastern Taiwan), and local administrative area (special municipality, provincial city, county-administered city, township, and aboriginal area). Results Of the regions, Northern Taiwan had the highest incidence rate at 139.6 per million person-years, followed by Central (132.8), Southern (131.8), and Eastern (128.4) Taiwan. Significantly higher standardized rate ratios (SRRs) were observed in Northern Taiwan (SRR = 1.06, 95% confidence interval [CI] = 1.02–1.10) and at the township level (SRR = 1.07, 95% CI = 1.03–1.11). Of the cities or counties, New Taipei City yielded the highest SRR (1.08), followed by Taipei City (SRR = 1.07). A comparison of the rates in the four regions and the remainder of Taiwan according to cancer type revealed that only the rate of neuroblastomas in Eastern Taiwan was significantly low. Trend analysis showed that the most significant increase in incidence rate was observed at the township level, with an annual percent change of 1.8% during the 15-year study period. Conclusions The high rate of childhood cancer in Northern Taiwan and at the township level deserves further attention. The potential impacts of environmental factors on the upward trend of childhood cancer incidence rate in townships warrant further investigation.

Extracellular Ca2+ and Mg2+ modulate aminoglycoside blockade of mechanotransducer channel-mediated Ca2+ entry in zebrafish hair cells: an in vivo study with the SIET

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 Ca(2+)-selective microelectrode to deflect hair bundles and simultaneously record the Ca(2+) flux, the inward Ca(2+) flux was detected at stereocilia of hair cells in 2- to ~4-day postfertilization embryos. Ca(2+) influx was blocked by MET channel blockers (BAPTA, La(3+), Gd(3+), and curare). In addition, 10 μM aminoglycoside antibiotics (neomycin and gentamicin) were found to effectively block Ca(2+) influx within 10 min. Elevating the external Ca(2+) level (0.2-2 mM) neutralized the effects of neomycin and gentamicin. However, elevating the Mg(2+) level up to 5 mM neutralized blockade by gentamicin but not by neomycin. This study demonstrated MET channel-mediated Ca(2+) entry at hair cells and showed that the SIET to be a sensitive approach for functionally assaying MET channels in zebrafish.

Treatment for childhood acute lymphoblastic leukemia in Taiwan: Taiwan Pediatric Oncology Group ALL-2002 study emphasizing optimal reinduction therapy and central nervous system preventive therapy without cranial radiation

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.

Outcomes Following Discontinuation of E. coli l-Asparaginase Upon Severe Allergic Reactions in Children With Acute Lymphoblastic Leukemia

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.

Incidences of Primary Soft Tissue Sarcoma Diagnosed on Extremities and Trunk Wall: A Population-Based Study in Taiwan

AbstractMost epidemiological studies of soft tissue sarcoma (STS) were performed in the Western countries, and only limited data highlighting that in the Asian population. The aim of this study is to conduct a comprehensive analysis for the incidence rates of STS in Taiwan.This was a population-based study analyzing the incidence rates and trends of the primary STS over extremities and trunk wall during 2003 to 2011 by using the nationwide Taiwan Cancer Registry. More specific analyses were conducted for subtypes. Incidence rates of overall STS by cities and counties were also investigated.A total of 3843 cases were diagnosed with STS during the study period, giving an age-standardized rate (ASR) of 1.63 per 100,000 person-years. Liposarcoma was the most frequent subtype, followed by undifferentiated pleomorphic sarcoma and leiomyosarcoma. STS was more frequently diagnosed in males and angiosarcoma was the most prominent sex-specific type. ASR increased with age in most of the STS subtypes and varied by histologic subtype. The incidence of peripheral primitive neuroectodermal tumor was highest in children, whereas rhabdomyosarcoma revealed a bimodal age distribution. Annual percent change (APC) of STS was 2.2%, and significant change in trend was only in males (APC, 3.5%, P < 0.05). Geographical variations indicated that New Taipei City had a significantly higher rate compared with the rest areas. Significantly lower rates were observed in 1 major offshore island.Incidence variations of STS by sexes, ages, histologic subtypes, and geographic regions were observed in Taiwanese population. The emerging factors associated STS incidence rates deserve further studies to verify.

Pediatric acute lymphoblastic leukemia with t(1;19)/TCF3-PBX1 in Taiwan

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.

Anion exchanger 1b in stereocilia is required for the functioning of mechanotransducer channels in lateral-line hair cells of zebrafish

The anion exchanger (AE) plays critical roles in physiological processes including CO2 transport and volume regulation in erythrocytes and acid-base regulation in renal tubules. Although expression of the AE in inner-ear hair cells was reported, its specific localization and function are still unclear. Using in situ hybridization, we found that the AE1b transcript is expressed in lateral-line hair cells of zebrafish larvae. An immunohistochemical analysis with a zebrafish-specific antibody localized AE1b to stereocilia of hair cells, and the expression was eliminated by morpholino knockdown of AE1b. A non-invasive, scanning ion-selective electrode technique was applied to analyze mechanotransducer (MET) channel-mediated Ca2+ influx at stereocilia of hair cells of intact fish. Ca2+ influx was effectively suppressed by AE1b morpholino knockdown and inhibitor (DIDS) treatment. Elevating external Ca2+ (0.2 to 2 mM) neutralized the inhibition of DIDS. Taken together, this study provides solid evidence to show that AE1b in stereocilia is required for the proper functioning of MET channels.