Purpose: While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head. Materials and Methods: We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens. Results: A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy. Conclusion Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

Purpose: While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head. Materials and Methods: We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens. Results: A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy. Conclusion Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

Purpose: While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head. Materials and Methods: We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens. Results: A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy. Conclusion Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

Purpose: Local excision (LE) is an alternative initial treatment for clinical T1 rectal cancer, and has avoided potential morbidity. This study aimed to evaluate the clinical outcomes of LE compared with total mesorectal excision (TME) for clinical T1 rectal cancer. Methods: Between January 2000 and December 2011, we retrospectively reviewed from multicenter data in patients with clinically suspected T1 rectal cancer treated with either LE or TME. Of 1,071 patients, 106 were treated with LE and 965 were treated with TME. The data were analyzed using propensity score matching, with each group comprising 91 patients. Results: After propensity score matching, the median follow-up time was 60.8 months (range, 0.6–150.6 months). After adjustment for the necessary variables, patients who underwent LE showed a significantly higher local recurrence rate than did those who underwent TME; however, there were no differences in disease-free survival and overall survival. In the multivariate analysis, age (hazard ratio [HR], 9.620; 95% confidence interval [CI], 3.415–27.098; P<0.001) and angiolymphatic invasion (HR, 3.63; 95% confidence interval, 1.33–9.89; P=0.012) were independently associated with overall survival. However, LE was neither associated with overall survival nor disease-free survival. Conclusion LE for clinical T1 rectal cancer yielded a higher local recurrence rate than did TME. Nevertheless, LE provided comparable overall survival rate and can be proposed as an optional treatment in terms of organ-preserving strategies.

High-risk human papillomaviruses (HPVs) are involved in the development of several human cancers, including oropharyngeal squamous cell carcinomas. However, many studies have demonstrated that HPV alone is not sufficient for the oncogenic transformation of normal human epithelial cells, indicating that additional cofactors are required for the oncogenic conversion of HPV-infected cells. Inasmuch as chronic inflammation is also closely associated with carcinogenesis, we investigated the effect of chronic exposure to tumor necrosis factor α (TNFα), the major proinflammatory cytokine, on oncogenesis in two immortalized oral keratinocyte cell lines, namely, HPV16-immortalized and human telomerase reverse transcriptase (hTERT)-immortalized cells. TNFα treatment led to the acquisition of malignant growth properties in HPV16-immortalized cells, such as (1) calcium resistance, (2) anchorage independence, and (3) increased cell proliferation in vivo. Moreover, TNFα increased the cancer stem cell-like population and stemness phenotype in HPV16-immortalized cells. However, such transforming effects were not observed in hTERT-immortalized cells, suggesting an HPV-specific role in TNFα-promoted oncogenesis. We also generated hTERT-immortalized cells that express HPV16 E6 and E7. Chronic TNFα exposure successfully induced the malignant growth and stemness phenotype in the E6-expressing cells but not in the control and E7-expressing cells. We further demonstrated that HPV16 E6 played a key role in TNFα-induced cancer stemness via suppression of the stemness-inhibiting microRNAs miR-203 and miR-200c. Overexpression of miR-203 and miR-200c suppressed cancer stemness in TNFα-treated HPV16-immortalized cells. Overall, our study suggests that chronic inflammation promotes cancer stemness in HPV-infected cells, thereby promoting HPV-associated oral carcinogenesis.

Poultry red mites (PRMs), Dermanyssus gallinae, are one of the most harmful ectoparasites of laying hens. Because of their public health impact, safe, effective methods to eradicate PRMs are greatly needed. Carbon dioxide (CO2 ) was shown to eradicate phytophagous mites;however, there is no evidence that PRMs can be eradicated by CO2. Thus, the efficacy of CO2, applied by direct-spraying and dry ice-generated exposure, for eradicating PRMs was investigated. Both treatments eradicated > 85% of PRMs within 24 h and 100% of PRMs by 120 h of post-treatment. Therefore, these novel approaches may be useful for eradicating PRMs in clinical settings.

OBJECTIVES: This study aimed to investigate the trajectory of change of diverse attention and working memory in Koreans from 4 to 40 years of age. METHODS: The data of 912 subjects from 4 to 15 years of age obtained from a previous standardization study of the computerized comprehensive attention test were merged with the newly obtained data of 150 subjects aged 16 to 40 years from this study. We evaluated the various kinds of attention, in which each subtest had five indicators. Working memory, with parameters such as number of correct responses and span, was also measured. RESULTS: Our findings indicated that attention developed as age increased, and it decreased or was maintained after a certain age. Selective and sustained attention developed rapidly in children and adolescents, until mid-teens or 20 s when it ceased development. Divided attention, however, developed up to approximately age 20. In addition, working memory developed until mid-teens or 20 s. CONCLUSION: We presented the standardized data on diverse kinds of attention and working memory in children, adolescents, and adults in Korea. We could recognize any patterns of change in attention and working memory with increasing age.
Adolescent ; Adult ; Child ; Humans ; Korea ; Memory, Short-Term ; Neuropsychological Tests

OBJECTIVES: This study was conducted in order to develop a computerized test to measure the level of mathematic achievement and related cognitive functions in children and adolescents in South Korea. METHODS: The computerized Comprehensive Learning Test-Mathematic (CLT-M) consists of the whole number computation test, enumeration of dot group test, number line estimation test, numeral comparing test (magnitude/distance), rapid automatized naming test, digit span test, and working memory test. To obtain the necessary data and to investigate the reliability and validity of this test, 399 children and adolescents from kindergarten to middle school were recruited. RESULTS: The internal consistency reliability of the CLT-M was high (Cronbach's alpha=0.76). Four factors explained 66.4% of the cumulative variances. In addition, the data for all of the CLT-M subtests were obtained. CONCLUSION: The computerized CLT-M can be used as a reliable and valid tool to evaluate the level of mathematical achievement and associated cognitive functions in Korean children and adolescents. This test can also be helpful to detect mathematical learning disabilities, including specific learning disorder with impairment in mathematics, in Korea.
Adolescent* ; Child* ; Cognition ; Dyscalculia ; Humans ; Korea ; Learning ; Learning Disorders ; Mathematics* ; Memory, Short-Term ; Reproducibility of Results ; Specific Learning Disorder

PURPOSE: The high mobility group box 1 (HMGB1) protein has roles in apoptosis and immune responses by acting as a ligand for receptor for advanced glycation end products (RAGE), Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 1. In particular, HMGB1/RAGE is involved in tumor metastasis by inducing matrix metalloproteinase 2 (MMP2) and MMP9 expression. We investigated the associations between genetic variations in HMGB1-related genes and disease-free survival (DFS) and overall survival (OS) in Korean female breast cancer patients. METHODS: A total of 2,027 patients in the Seoul Breast Cancer Study were included in the analysis. One hundred sixteen single nucleotide polymorphisms (SNPs) were extracted from eight genes. A multivariate Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) of each SNP. The effects of the SNPs on breast cancer prognosis were assessed at cumulative levels with polygenic risk scores. RESULTS: The SNPs significantly associated with DFS were rs243867 (hazard ratio, 1.26; 95% CI, 1.05–1.50) and rs243842 (hazard ratio, 1.24; 95% CI, 1.03–1.50); both SNPs were in MMP2. The SNPs significantly associated with OS were rs243842 in MMP2 (hazard ratio, 1.33; 95% CI 1.03–1.71), rs4145277 in HMGB1 (hazard ratio, 1.29; 95% CI, 1.00–1.66), rs7656411 in TLR2 (hazard ratio, 0.76; 95% CI, 0.60–0.98), and rs7045953 in TLR4 (hazard ratio, 0.50; 95% CI, 0.29–0.84). The polygenic risk score results for the DFS and OS patients showed third tertile hazard ratios of 1.72 (95% CI, 1.27–2.34) and 2.75 (95% CI, 1.79–4.23), respectively, over their first tertile references. CONCLUSION: The results of the present study indicate that genetic polymorphisms in HMGB1-related genes are related to breast cancer prognosis in Korean women.
Advanced Glycosylation End Product-Specific Receptor ; Apoptosis ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Female ; Genetic Predisposition to Disease* ; Genetic Variation ; HMGB1 Protein ; Humans ; Matrix Metalloproteinase 2 ; Myeloid Cells ; Neoplasm Metastasis ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Prognosis* ; Proportional Hazards Models ; Seoul ; Toll-Like Receptors

OBJECTIVES: The aim of this study was to develop the computerized Comprehensive Learning Test-Reading (CLT-R) to evaluate the cognitive processes and achievements related to their basic reading ability and identify dyslexia in children and adolescents in South Korea. We also obtained the normative data and evaluated the reliability and validity of the test. METHODS: We developed the CLT-R, including the word attack/nonword decoding, paragraph reading, sound blending, nonword repetition, rapid automatized naming, letter-sound matching, visual attention, orthography awareness, and digit span tests, for the purpose of diagnosing dyslexia. We investigated the reliability and validity of the tests and gathered the normative data from 399 subjects (male 48.9%), aged 5-14 years, from the last grade in kindergarten to middle school, dwelling in Seoul and Gyeonggi Province, South Korea. RESULTS: No statistical differences were observed between the means of the tests and retests of the CAT. The mean of the correlation coefficient of the test-retest scores was 0.85. According to the construct validity test calculated by principal constant analysis using the oblique rotation method, 4 factors explained 70.0% of the cumulative variances. In addition, the normative data were obtained for all of the CLT-R subtests. CONCLUSION: The computerized CLT-R can be used as a reliable and valid tool to evaluate the reading achievement and reading related cognitive process in Korean children and adolescents in schools, clinics, and research institutes.
Academies and Institutes ; Adolescent* ; Animals ; Cats ; Child* ; Diagnosis* ; Dyslexia* ; Gyeonggi-do ; Humans ; Korea ; Learning* ; Methods ; Reading ; Reproducibility of Results ; Seoul