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// Pai-Feng Kao 1, 6, * , Ju-Chi Liu 1, 6, * , Yi-Ping Hsu 1 , Li-Chin Sung 1, 6 , Tsung-Yeh Yang 1 , Wen-Rui Hao 1 , Ying-Chin Lin 2, 3 and Szu-Yuan Wu 4, 5, 6, 7 1 Division of Cardiovascular Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan 2 Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, New Taipei, Taiwan 3 Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 4 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 5 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 6 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 7 Department of Biotechnology, Hungkuang University, Taichung, Taiwan * These authors have contributed equally to this work Correspondence to: Szu-Yuan Wu, email: szuyuanwu5399@gmail.com Keywords: influenza vaccination; atrial fibrillation; ischemic stroke Received: June 11, 2017 Accepted: July 26, 2017 Published: November 09, 2017 ABSTRACT Purpose: Atrial fibrillation (AF) is associated with the risk of ischemic stroke, regardless of the administration of appropriate antithrombotic prophylaxis. This study investigated whether influenza vaccination is associated with the risk of ischemic stroke, to determine a solution to reduce this risk in patients with AF. Methods: We used data from the Taiwan National Health Insurance Research Database. The study cohort comprised all patients diagnosed as having AF (n = 14 454) before January 1, 2005; these patients were followed until December 31, 2012. The index date was January 1, 2005. A propensity score was derived using a logistic regression model to estimate the effect of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A Cox proportional hazard model was used to calculate the hazard ratios (HRs) of ischemic stroke in vaccinated and unvaccinated patients with AF. Results: We included 6570 patients (2547 [38.77%] with and 4023 [61.23%] without influenza vaccination). The adjusted HRs (aHRs) of ischemic stroke were lower in the vaccinated patients than in the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs = 0.59, 0.50, and 0.55; P < 0.001, P < 0.001, and P < 0.001, respectively). Conclusions: Influenza vaccination might exert a dose-response effect against ischemic stroke in patients with AF who have risk factors for ischemic stroke by reducing the incidence of ischemic stroke, particularly in those aged 65–74 and ≥75 y.

// Ju-Chi Liu 1, 4, * , Tsung-Yeh Yang 1, * , Yi-Ping Hsu 1 , Wen-Rui Hao 1 , Pai-Feng Kao 1, 4 , Li-Chin Sung 1, 4 , Chun-Chao Chen 1 , Szu-Yuan Wu 2, 3, 4, 5 1 Division of Cardiovascular Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan 2 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 3 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 4 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 5 Department of Biotechnology, Hungkuang University, Taichung, Taiwan * Co-first authors, These authors contributed equally to this work Correspondence to: Szu-Yuan Wu, email: szuyuanwu5399@gmail.com Keywords: statins, COPD, lung cancer Received: March 09, 2016 Accepted: July 09, 2016 Published: August 09, 2016 ABSTRACT Purpose: Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk. We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential. Results: After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37). Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly. By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively). Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use). Materials and Methods: The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan ( n = 116,017) between January 1, 2001 and December 31, 2012. Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not. Patients were followed up to assess lung cancer risk or protective factors. In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use. The index date of statin use was the COPD confirmation date. To examine the dose–response relationship, we categorized statin use into four groups in each cohort: 365 cumulative defined daily doses (cDDDs). Patients receiving < 28 cDDDs were defined as nonstatin users. Conclusions: Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients. Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential.

// Ju-Chi Liu 1, 4, * , Wen-Rui Hao 1, * , Yi-Ping Hsu 1 , Li-Chin Sung 1, 4 , Pai-Feng Kao 1, 4 , Chao-Feng Lin 1 , Alexander T.H. Wu 6 , Kevin Sheng-Po Yuan 7 , Szu-Yuan Wu 2, 3, 4, 5 1 Division of Cardiovascular Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan 2 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 3 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 4 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 5 Department of Biotechnology, Hungkuang University, Taichung, Taiwan 6 Ph.D. Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan 7 Department of Otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Szu-Yuan Wu, email: szuyuanwu5399@gmail.com Keywords: statins, chronic obstructive pulmonary disease, colon cancer Received: March 22, 2016 Accepted: June 27, 2016 Published: August 12, 2016 ABSTRACT Purpose: We evaluated the chemopreventive effect of statins on colon cancer in patients with chronic obstructive pulmonary disease (COPD) and identified the statin exerting the strongest chemopreventive effect. Methods: Using the National Health Insurance Research Database, we identified patients who received a COPD diagnosis in Taiwan between January 1, 2001, and December 31, 2012, and included them in the study cohort. Each patient was followed to assess the colon cancer risk and protective factors. A propensity score was derived using a logistic regression model to estimate the effect of statins by accounting for covariates predicted during the intervention (statins). To examine the dose–response relationship, we categorized statin doses into four groups in each cohort [ 365 cumulative defined daily dose]. Results: Compared with the statin nonusers, the adjusted hazard ratio (aHR) for colon cancer decreased in the statin users (aHR = 0.52, 95% confidence interval = 0.44, 0.62). Hydrophilic statins exerted a stronger preventive effect against colon cancer. Regarding the statin type, lovastatin, pravastatin, and fluvastatin nonsignificantly reduced the colon cancer risk in the patients with COPD. Compared with the statin nonusers, the aHRs for colon cancer decreased in the individual statin users (rosuvastatin, simvastatin, and atorvastatin: aHRs = 0.28, 0.64, and 0.65, respectively). In the sensitivity analysis, statins dose-dependently reduced the colon cancer risk. Conclusions: Statins dose-dependently exert significant chemopreventive effects on colon cancer in patients with COPD, with rosuvastatin exerting the largest chemopreventive effect.

// Szu-Yuan Wu 1, 2, 3, 4 , Alexander T.H. Wu 5 , Shing-Hwa Liu 1, 6, 7 1 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 2 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 3 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 4 Department of Biotechnology, Hungkuang University, Taichung, Taiwan 5 The Ph.D. Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan 6 Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan 7 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan Correspondence to: Shing-Hwa Liu, email: shinghwaliu@ntu.edu.tw Keywords: miR-17-5p, OC3 cells, p53, radiation, apoptosis Received: February 27, 2016 Accepted: May 26, 2016 Published: June 06, 2016 ABSTRACT Betel nut chewing is associated with oral cavity cancer. Radiotherapy is one of the therapeutic approaches. Here, we used miR-17-5p antisense oligonucleotides (AS-ODNs) and human apoptosis protein array to clarify which apoptosis-related proteins are increased or decreased by miR-17-5p in betel nut chewing- oral squamous cell carcinoma OC3 cells. Furthermore, miR-17-5p AS-ODN was used to evaluate the radio-sensitization effects both in vitro and in vivo . An OC3 xenograft tumor model in severe combined immunodeficiency mice was used to determine the effect of miR-17-5p AS ODN on tumor irradiation. We simultaneously detected the relative expressions of 35 apoptosis-related proteins in irradiated OC3 cells that were treated with miR-17-5p AS-ODN or a control ODN. Several proteins, including p21, p53, TNF RI, FADD, cIAP-1, HIF-1α, and TRAIL R1, were found to be up- or downregulated by miR-17-5p in OC3 cells; their expression patterns were also confirmed by Western blotting. We further clarified the role of p53 in irradiated OC3 cells, using a p53 overexpression strategy. The results revealed that the enhancement of p53 expression significantly enhanced radiation-induced G2/M arrest of the OC3 cells. In the in vivo study, treatment of miR-17-5p AS-ODN before irradiation significantly enhanced p53 expression and reduced tumor growth. These results suggest that miR-17-5p increases or decreases apoptosis-related proteins in irradiated OC3 cells; its effect on p53 protein expression contributes to the modulation of the radiosensitivity of the OC3 cells.

// Shih-Chiung Lai 1, * ,Wei-Chun Lin 2, * , Chien-Hsin Chen 3 , Szu-Yuan Wu 4, 5, 6, 7 1 Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan 2 Department of Cancer Research Center, Wan Fang Hospital, Taipei Medical University, Taiwan 3 Department of Colorectal Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 4 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 5 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 6 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 7 Department of Biotechnology, Hungkuang University, Taichung, Taiwan * These authors contributed equally to this work and are joint first authors Correspondence to: Szu-Yuan Wu, email: szuyuanwu5399@gmail.com Keywords: cancer-related fatigue questionnaire, reliability, validity Received: October 17, 2016 Accepted: February 06, 2017 Published: March 16, 2017 ABSTRACT Purpose: We prospectively designed a Taiwan cancer-related fatigue cognition questionnaire, version 1.0 (TCRFCQ-V1.0), for Taiwanese patients with cancer and investigated the reliability and validity of this questionnaire. Results: The completion rate of the TCRFCQ-V1.0 was high (97% of the patients completed all items), and the rate of missing data was low (0.2%–1.1% for each item). Moreover, the Cronbach alpha value was 0.889. We eliminated 5 items because their respective Cronbach alpha values were higher than the total mean value of Cronbach’s alpha. Overall, the TCRFCQ-V1.0 had adequate Cronbach alpha coefficients (range, from 0.882 to 0.889). In addition, the results of Bartlett’s test were significant (chi-squared, 2390.11; p 1, and the scree plot indicated no flattening factors. Overall, 28 items achieved a factor loading of ≥ 0.55. Materials and Methods: We enrolled patients with cancer who were aged > 18 years, had received a pathological diagnosis of cancer, and had undergone cancer treatments such as surgery, chemotherapy, radiotherapy, or concurrent chemoradiotherapy at a single institute in Taiwan. Of the identified 167 eligible patients, 161 (96.4%) were approached. Of these patients, 6 (7.2%) declined to participate and 155 (92.8%) were interviewed. The initial 43 items in the TCRFCQ-V1.0 were assessed for ceiling and floor effects. Conclusions: The TCRFCQ-V1.0 is a reliable and valid instrument for measuring CRF cognition in Taiwanese patients with cancer.

// Yen-Kuang Lin 1 , Han-Lin Hsu 2,3 , Wei-Cheng Lin 4 , Jer-Hwa Chang 2,3 , Yw-Chun Chang 4 , Chia-Lun Chang 5 , Kevin Sheng-Po Yuan 6 , Alexander T.H. Wu 7 and Szu-Yuan Wu 8,9,10,11* 1 Biostatistics Center and School of Public Health, Taipei Medical University, Taipei, Taiwan 2 Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 3 School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan 4 Division of Thoracic Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 5 Department of Hemato-Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 6 Department of Otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 7 Ph.D. Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan 8 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 9 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 10 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 11 Department of Biotechnology, Hungkuang University, Taichung, Taiwan Correspondence to: Szu-Yuan Wu, email: // Keywords : lung cancer, pN2, survival, adjuvant radiotherapy Received : August 26, 2016 Accepted : October 28, 2016 Published : November 09, 2016 Abstract Purpose: Few large, prospective, randomized studies have compared the effects of postoperative radiotherapy (PORT) in pathological N2 (pN2) with those of surgical resection alone. in terms of long-term survival in lung adenocarcinoma (adenoCA; wild-type [WT] epidermal growth factor receptor [EGFR]) and squamous cell carcinoma (squCA) settings. This nationwide cohort study clarifies the role of PORT in the survival of pN2 lung adenoCA (WT EGFR) and squCA patients Patients and Methods: We analyzed data of patients with adenoCA (WT EGFR) and squCA collected from the Taiwan Cancer Registry database. The patients were categorized into five groups according to the treatment modality: Group 1 (surgery alone), Group 2 (adjuvant chemotherapy [CT] alone), Group 3 (adjuvant radiotherapy [RT] alone), Group 4 (adjuvant concurrent chemoradiotherapy [CCRT]), and Group 5 (adjuvant sequential CT and intensity-modulated RT [IMRT]). Results: We enrolled 588 lung adenoCA (WT EGFR) and squCA patients without distant metastasis. After adjustments for age at surgery, surgical years, and Charlson comorbidity index scores, the multivariate Cox regression analysis demonstrated that adjusted HRs (aHRs; 95% confidence intervals [CIs]) for the overall mortality of female lung adenoCA (WT EGFR) patients were 0.257 (0.111-0.594), 0.530 (0.226-1.243), 0.192 (0.069-0.534), and 0.399 (0.172-0.928) in Groups 2, 3, 4, and 5, respectively. For male lung squCA patients, the aHRs (95% CIs) for overall mortality were 0.269 (0.160-0.451), 0.802 (0.458-1.327), 0.597 (0.358-0.998), and 0.456 (0.265-0.783) in Groups 2, 3, 4, and 5, respectively. Conclusions: Adjuvant CCRT or sequential CT and IMRT at ≥5000 cGy significantly reduced the mortality rate of female lung adenoCA (WT EGFR) and male squCA pN2 patients.

// Jer-Hwa Chang 1,2 , Chia-Che Wu 3 , Kevin Sheng-Po Yuan 3 , Alexander T.H. Wu 4 and Szu-Yuan Wu 5,6,7 1 Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 2 School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan 3 Department of Otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 4 The Ph.D. Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan 5 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 6 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 7 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Correspondence to: Szu-Yuan Wu, email: // Keywords : head and neck cancer; recurrence; incidence; survival; prognostic factors Received : June 09, 2016 Accepted : February 15, 2017 Published : March 17, 2017 Abstract Purpose: For locoregionally recurrent head and neck squamous cell carcinoma (HNSCC), appropriate therapeutic decisions remain unclear. We examined the treatment outcomes of a national cohort to determine suitable treatments for and prognostic factors in patients with locoregionally recurrent HNSCCs at different stages and sites. Patients and methods: We analyzed data of >20-year-old patients with HNSCC at American Joint Committee on Cancer clinical stages I–IV without metastasis from Taiwan National Health Insurance and cancer registry databases. The index date was the date of recurrent HNSCC diagnosis. Recurrent HNSCC was defined as the annotation of locoregional recurrence with tissue proof in cancer registry databases. The enrolled patients were categorized into three groups: Group 1 comprised those undergoing chemotherapy (CT) alone; Group 2 comprised those receiving reirradiation (re-RT) alone (total radiation dose ≥ 60 Gy through intensity modulation radiation therapy [IMRT]); Group 3 comprised those receiving concurrent chemoradiotherapy (CCRT) alone (irradiation total dose ≥60 Gy through IMRT); and Group 4 comprised those receiving salvage surgery with or without RT or CT. Results: We enrolled 4,839 and 28,664 HNSCC patients with and without locoregional recurrence, respectively (median follow-up, 3.25 years). Locoregional recurrence rate and incidence were 14.44% and 40.73 per 1,000 person-years, respectively. Age ≥ 65 years, Charlson comorbidity index (CCI) score > 6, advanced clinical stage at first diagnosis, and recurrence-free interval < 1 year were significant independent prognostic risk factors for overall survival as per univariate and multivariate Cox regression analyses. After adjusting for age, sex, CCI scores, clinical stage at first diagnosis, and recurrence-free interval, adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for overall mortality in recurrent clinical stages I and II were 0.63 (0.45–0.89, p = 0.009), 0.65 (0.52–0.83, p < 0.001), and 0.32 (0.26–0.40, p < 0.001) in Groups 2, 3, and 4, respectively, whereas they were 1.23 (0.99–1.52, p = 0.062), 0.69 (0.60–0.79, p < 0.001), and 0.39 (0.34–0.44, p < 0.001) for Groups 2, 3, and 4, respectively, for overall mortality in recurrent clinical stage III and IV. Conclusions: Age, CCI score, clinical stage at first diagnosis, and recurrence-free interval are significant independent prognostic factors for overall survival of recurrent HNSCC patients. Regardless of recurrence stage or site, salvage surgery is the recommended first recurrent HNSCC treatment choice. Re-RT alone and CCRT are more suitable for inoperable recurrent early-stage oral and nonoral cavity recurrent HNSCCs, respectively.