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Purpose No large-scale, prospective, randomized study has evaluated the effect of thoracic surgery on patients with unresectable stage IIIB–IV epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma who received and responded to EGFR tyrosine kinase inhibitor (TKI) treatment. Therefore, we designed a propensity-score-matched, nationwide, population-based, cohort study to investigate the effects of thoracic surgery on patients with EGFR-mutant lung adenocarcinoma. Patients and Methods We included patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinoma and categorized them into two groups according to their treatment modalities and compared their outcomes: the case group consisted of patients who underwent thoracic surgery for lung tumors after receiving and responding to EGFR-TKI treatment and the comparison group consisted of patients who received EGFR-TKI treatment alone until tumor progression. Patients in both groups were matched at a ratio of 1:4. Results The matching process yielded a final cohort of 1395 patients (279 and 1,116 in the case and comparison groups, respectively) who were eligible for further analysis. According to multivariable Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval [CI]) for thoracic surgery for lung tumors after EGFR-TKI use and tumor response (group 2) compared with EGFR-TKI treatment alone (group 1) was 0.445 (0.351–0.564). Conclusions Thoracic surgery prolonged overall survival in patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinoma who received and responded to EGFR-TKI treatment.

Graphical abstract, MAX dimerization (MXD) protein 3 (MXD3) is a member of the MXD family of basic-helix-loop-helix-leucine-zipper (bHLHZ) transcription factors that plays pivotal roles in cell cycle progression and cell proliferation. However, there is insufficient scientific evidence on the pathogenic roles of MXD3 in various cancers and whether MXD3 plays a role in the immuno-oncology context of the tumor microenvironment, pathogenesis, prognosis, and therapeutic response of different tumors through certain common molecular mechanisms; thus, we saw a need to conduct the present in silico pan-cancer study. Using various computational tools, we interrogated the role of MXD3 in tumor immune infiltration, immune evasion, tumor progression, therapy response, and prognosis of cohorts from various cancer types. Our results indicated that MXD3 was aberrantly expressed in almost all The Cancer Genome Atlas (TCGA) cancer types and subtypes and was associated with the tumor stage, metastasis, and worse prognoses of various cohorts. Our results also suggested that MXD3 is associated with tumor immune evasion via different mechanisms involving T-cell exclusion in different cancer types and by tumor infiltration of immune cells in thymoma (THYM), liver hepatocellular carcinoma (LIHC), and head and neck squamous cell carcinoma (HNSC). Methylation of MXD3 was inversely associated with messenger (m)RNA expression levels and mediated dysfunctional T-cell phenotypes and worse prognoses of cohorts from different cancer types. Finally, we found that genetic alterations and oncogenic features of MXD3 were concomitantly associated with deregulation of the DBN1, RAB24, SLC34A1, PRELID1, LMAN2, F12, GRK6, RGS14, PRR7, and PFN3 genes and were connected to phospholipid transport and ion homeostasis. Our results also suggested that MXD3 expression is associated with immune or chemotherapeutic outcomes in various cancers. In addition, higher MXD3 expression levels were associated with decreased sensitivity of cancer cell lines to several mitogen-activated protein kinase kinase (MEK) inhibitors but led to increased activities of other kinase inhibitors, including Akt inhibitors. Interestingly, MXD3 exhibited higher predictive power for response outcomes and overall survival of immune checkpoint blockade sub-cohorts than three of seven standardized biomarkers. Altogether, our study strongly suggests that MXD3 is an immune-oncogenic molecule and could serve as a biomarker for cancer detection, prognosis, therapeutic design, and follow-up.

BACKGROUND No evidence is currently available to estimate the outcomes of intensity-modulated radiation therapy (IMRT) and surgery for patients with early oral cavity squamous cell carcinoma (E-OCSCC). METHODS We recruited patients from the Taiwan Cancer Registry Database who had received a diagnosis of E-OCSCC. Propensity score matching was performed, and Cox proportional hazards model was used to analyze all-cause mortality. RESULTS In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) for surgery compared with definitive IMRT, T2N0M0 compared with T1N0M0, and male patients compared with female patients were 0.303 (0.245, 0.375), 1.340 (1.077, 1.668), and 2.012 (1.432, 2.826), respectively. The aHRs (95% CIs) for age 61 to 70, 71 to 80, and ≧81 years compared with

Purpose To investigate the outcomes of adjuvant whole breast radiation therapy (WBRT) in patients with invasive ductal carcinoma of the breast (breast IDC) receiving preoperative systemic therapy (PST) and breast-conserving surgery (BCS), and their prognostic factors, considering overall survival (OS), locoregional recurrence (LRR), distant metastasis (DM), and disease-free survival. Patients and methods Patients diagnosed as having breast IDC and receiving PST followed by BCS were recruited and categorized by treatment into non-breast radiation therapy [BRT] (control) and WBRT (case) groups, respectively. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs). Results Multivariate Cox regression analyses indicated that non-BRT, cN3, and pathologic residual tumor (ypT2–4) or nodal (ypN2–3) stages were poor prognostic factors for OS. The adjusted HRs (aHRs; 95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.14 (0.03–0.81), 0.32 (0.16–0.64), 0.43 (0.23–0.79), 0.23 (0.13–0.42), 0.52 (0.20–1.33), and 0.34 (0.13–0.87) in the ypT0, ypT1, ypT2–4, ypN0, ypN1, and ypN2–3 stages, respectively. The aHRs (95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.09 (0.00–4.07), 0.46 (0.26–0.83), 0.18 (0.06–0.51), 0.28 (0.06–1.34), 0.25 (0.10–0.63), 0.47 (0.23–0.88), and 0.32 in the cT0–1, cT2, cT3, cT4, cN0, cN1, and cN2–3 stages, respectively. The WBRT group exhibited significantly better LRR-free and DM-free survival than the non-BRT group, regardless of the clinical T or N stage or pathologic response after PST. Conclusion WBRT might lead to superior OS and LRR-free and DM-free survival compared with the non-BRT group, regardless of the initial clinical TN stage or pathologic response., Highlights • Outcome patterns of adjuvant RT for patients with breast cancer receiving preoperative systemic therapy and breast-conserving surgery. • Non-breast radiation therapy, cN3, pathologic residual tumor (ypT2–4), or nodal (ypN2–3) stages are poor prognostic factors for survival. • The beneficial effects of RT are superior OS and LRR-free and DM-free survival compared with the non-RT group.

Purpose To use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM). Patients and methods We enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis. Results After multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52–0.81, P, Highlights • No large-scale study has estimated detailed outcome patterns of postmastectomy radiation therapy stratified based on postchemotherapy pathologic stages in breast cancer receiving neoadjuvant chemotherapy and total mastectomy. • We used pathologic indicators to determine which patients benefit from PMRT for breast cancer after NACT and TM. • For patients with breast cancer ypT3–4, ypN2–3, or pathologic stages IIIA–IIIC receiving NACT and TM, PMRT should be performed if it is associated with survival benefits, regardless of their clinical stages.

Purpose: To identify novel radiological features and clinical characteristics to improve diagnostic criteria for early detection of small hepatocellular carcinoma (HCC). Patients and Methods: We retrospectively recruited asymptomatic patients with no history of HCC but a high risk of HCC in whom a new, solitary, well-defined, solid nodule between 10 and 20 mm was detected through a screening ultrasound. We retrospectively collected all clinical data, and patients were examined using dynamic contrast-enhanced computed tomography or magnetic resonance imaging; subsequently, fine-needle biopsy was performed. A multivariate analysis of the predictors of small HCCs was performed by fitting a multiple logistic regression model with the stepwise variable selection method. Results: In total, 392 and 347 patients with a small liver nodule received a final pathologic confirmation of HCC and non-HCC, respectively. The estimated odds ratios and 95% confidence intervals of tumor size > 12.45 mm, age > 56.61 years, liver cirrhosis, hepatitis C virus (HCV) carrier status, ln alpha-fetoprotein (AFP) > 1.954, arterial phase enhancement, and portal or venous phase washout appearance without arterial phase enhancement were 2.0735 (1.4746-2.9155), 1.8878 (1.2949-2.7521), 1.6927 (1.1294-2.5369), 1.6186 (1.0347-2.5321), 2.0297 (1.3342-3.0876), 3.7451 (2.3845-5.8821), and 2.0327 (1.3500-3.0608), respectively. The area under the receiver operating characteristic curves for the diagnosis of small HCCs was 0.79 for arterial phase enhancement and 0.75 for portal or venous phase washout appearance without arterial phase enhancement. Conclusion: Clinical and contrast-enhanced image features are valuable in the prediction model for the detection and early diagnosis of small HCCs in patients with a high risk of HCC. In addition to negative portal or venous washout and negative arterial enhancement in images, age > 56.61 years, tumor size > 12.45 mm, HCV carrier status, and ln(AFP) > 1.954, are useful indicators for the early detection of small HCCs.

Objective: We conducted this propensity score (PS)-matched, nationwide, population-based cohort study to estimate the effects of adjuvant oral or intravenous (IV) fluoropyrimidine in patients with high-risk stage II or III colon adenocarcinoma. Design: Using PS matching, we minimized the confounding effects on adjuvant oral or IV fluoropyrimidine outcomes in patients with high-risk stage II or III resectable colon adenocarcinoma. Setting: We selected patients from the Taiwan Cancer Registry database receiving adjuvant fluoropyrimidine monotherapy and divided them into those receiving IV fluoropyrimidine (IV group) and those receiving oral fluoropyrimidine (oral group). Results: In both univariate and multivariate Cox regression analyses, the adjusted hazard ratio (aHR) derived for the oral group was 1.34 (95% CI: 1.19-1.51) compared with the IV group. Moreover, in both univariate and multivariate analyses, aHR derived for significant independent prognostic risk factors for poor overall survival were male sex, age ≥ 60 years old, pathologic stage III, right-sided colon cancer, low income, and high Charlson comorbidity index. However, intergroup differences were not significant among female patients or patients < 60 years old on multivariate analysis, including no difference in overall survival. Conclusions: Adjuvant IV fluoropyrimidine is more suitable than adjuvant oral fluoropyrimidine for patients with stage II colon adenocarcinoma who have high-risk pathologic features or stage III colon adenocarcinoma.

BACKGROUND To date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast intraductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). PATIENTS AND METHODS : We enrolled 294 women with left-breast IDC at clinical stages IA–IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs). RESULTS In the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44–0.94) was a significant independent prognostic factor for all-cause death (P = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24–0.71; P = 0.0017) and 0.37 (0.22–0.63; P = 0.0004), respectively, compared with the no adjuvant WBRT group. The aHR (95% CI) of breast cancer death for adjuvant WBRT was 0.54 (0.44–0.85; P = 0.0201) compared with no adjuvant WBRT group. CONCLUSION Adjuvant WBRT was associated with a decrease in all-cause death, breast cancer death, LRR, and DM in women with left IDC and HFrEF compared with no adjuvant WBRT.

The etiology of sudden sensorineural hearing loss (SSNHL) has been unclear until now. Understanding its potential etiology is crucial for the development of preventive medicine. In this study, we investigated the association between acute upper respiratory tract infections (URIs) and SSNHL risk. We conducted a case-crossover study by using the longitudinal health insurance database derived from the National Health Insurance Research Database in Taiwan. Individual acute URI between the case and control periods was reviewed. Multivariable conditional logistic regression models were used to estimate the adjusted odds ratios (aORs) of SSNHL risk associated with acute URIs after adjustments for potential confounders. In total, 1131 patients with SSNHL between 2010 and 2013 fulfilled our inclusion criteria and were included. The aOR (95% confidence interval [CI]) for SSNHL was 1.57 (1.20–2.05) in relation to acute URIs one month before the index date. Moreover, the aORs (95% CIs) of the female and young to middle-aged (≤65 years) populations were 1.63 (1.13–2.36) and 1.76 (1.29–2.40), respectively. In addition, the association between SSNHL and acute URIs was decreased over time. The aOR for SSNHL was 1.25 (1.01–1.56) in relation to acute URIs three months before the index date. Acute URIs increase SSNHL risk and are a potential risk factor for SSNHL. The establishment of a feasible health policy for the prevention of acute URIs is crucial for SSNHL prevention, particularly in female, and young to middle-aged populations.

Purpose: To investigate whether chronic obstructive pulmonary disease (COPD) and COPD severity (acute exacerbation of COPD (AECOPD)) affect the survival outcomes of patients with colon adenocarcinoma receiving standard treatments. Methods: From the Taiwan Cancer Registry Database, we recruited patients with clinical stage I–III colon adenocarcinoma who had received surgery. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into COPD and non-COPD (Group 1 and 2) groups through propensity score matching. Results: In total, 1512 patients were eligible for further comparative analysis between non-COPD (1008 patients) and COPD (504 patients) cohorts. In the multivariate Cox regression analysis, the adjusted hazard ratio (aHR, 95% confidence interval (CI)) for all-cause mortality for Group 1 compared with Group 2 was 1.17 (1.03, 1.29). In patients with colon adenocarcinoma undergoing curative resection, the aHRs (95% CIs) for all-cause mortality in patients with hospitalization frequencies of ≥1 and ≥2 times for AECOPD within 1 year before adenocarcinoma diagnosis were 1.08 (1.03, 1.51) and 1.55 (1.15, 2.09), respectively, compared with those without AECOPD. Conclusion: In patients with colon adenocarcinoma undergoing curative resection, COPD was associated with worse survival outcomes. Being hospitalized at least once for AECOPD within 1 year before colon adenocarcinoma diagnosis was an independent risk factor for poor overall survival in these patients, and a higher number of hospitalizations for AECOPD within 1 year before diagnosis was associated with poorer survival. Our study highlights the importance of COPD management, particularly the identification of frequent exacerbators and the prevention of AECOPD before standard colon adenocarcinoma treatments are applied.

Purpose: The survival effect of current smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with rectal adenocarcinoma undergoing curative resection. Methods: We recruited patients with clinical stage I–IIIC rectal adenocarcinoma from the Taiwan Cancer Registry Database who had received surgery. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into two groups by using propensity score matching based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD). Results: In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR, 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.25 (1.04–1.51). The aHRs (95% cis) of all-cause mortality for frequency of ≥1 hospitalizations for COPDAE or ≥2 hospitalizations within 1 year before diagnosis were 1.17 (1.05–1.51) and 1.48 (1.03–2.41) compared with no COPDAE in patients with rectal adenocarcinoma undergoing curative resection. Conclusion: In patients with rectal adenocarcinoma undergoing curative resection, being a current smoker with COPD (Group 1) was associated with worse survival outcomes than being a nonsmoker without COPD (Group 2). Being hospitalized at least once for COPDAE within 1 year before the diagnosis of rectal adenocarcinoma is an independent risk factor for poor overall survival in these patients, and a higher number of hospitalizations for COPDAE within 1 year before diagnosis was associated with poorer survival.

BACKGROUNDTo date, no data are available regarding the effect of chronic obstruction pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on survival in patients with lung squamous cell carcinoma (SCC) receiving definitive concurrent chemoradiotherapy (CCRT).PATIENTS AND METHODSCurrent-smoking patients with clinical stage IIIA-IIIB, lung SCC who had received standard definitive CCRT and categorized them into two groups based on their COPD status to compare overall survival outcomes. We also examined the effects of COPD severity (0, 1, or ≥2 hospitalizations for COPDA within 1 year before CCRT). The aHRs (95% CIs) of lung cancer death for 1 and ≥2 hospitalizations for COPDAE within 1 year before CCRT were 1.21 (1.09, 1.39) and 1.63 (1.34, 1.97), respectively, compared with no hospitalization for COPDAE.RESULTSIn the inverse probability of treatment weighting (IPTW)-adjusted model, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) of all-cause death for COPD was 1.06 (1.07, 1.71) compared with the non-COPD group. Moreover, in the IPTW-adjusted model, the aHRs (95% CIs) of 1 and ≥2 hospitalizations for COPDAE within 1 year before CCRT were 1.29 (1.16, 1.43) and 1.77 (1.41, 2.13), respectively, compared with no hospitalization for COPDAE.CONCLUSIONCOPD and its severity are significant independent risk factors for all-cause death in patients with stage IIIA-IIIB lung SCC receiving definitive CCRT. Hospitalization for COPDAE within 1 year before CCRT is the significant independent risk factors for lung cancer death in the patients with stages IIIA-IIIB lung SCC receiving definitive CCRT.

BACKGROUND AND PURPOSE To determine the long-term survival outcomes of and prognostic factors for survival in patients with a ruptured intracranial aneurysm (RIA) who underwent endovascular coil embolization or surgical clipping. METHODS We selected patients who had received a diagnosis of RIA between January 1, 2011 and December 31, 2017. Propensity score matching was performed, and Cox proportional hazards model curves were plotted to analyze all-cause mortality in patients undergoing different treatments. RESULTS The matching process yielded a final cohort of 8102 patients (4051 and 4051 in endovascular coil embolization and surgical clipping groups, respectively) who were eligible for inclusion. In multivariate Cox regression analyses, the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for endovascular coil embolization compared with surgical clipping were 0.87 (95% CI, 0.79-0.97). The aHRs for the ages of 65 to 74, 75 to 84, and ≥85 years compared with the ages of 20 to 64 years were 1.82 (95% CI, 1.60-2.07), 3.35 (95% CI, 2.93-3.84), and 6.99 (95% CI, 5.51-8.86), respectively. Surgical clipping; old age; male sex; treatment during 2011 to 2013; presence of diabetes, congestive heart failure, hypertension, chronic kidney disease, or end-stage renal disease; history of stroke or transient ischemic attack; Charlson Comorbidity Index ≥2; attendance of nonacademic hospitals; and low income were significant independent prognostic factors for poor survival. CONCLUSIONS Compared with surgical clipping, endovascular coil embolization led to more favorable survival outcomes in patients with RIAs.

Simple Summary No data are available regarding the effect of chronic obstruction pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on survival in patients with lung squamous cell carcinoma (SCC) receiving definitive concurrent chemoradiotherapy (CCRT). This study is the first to examine the survival impact of COPD in patients with lung SCC receiving definitive CCRT. COPD and its severity are significant independent risk factors for all-cause mortality in patients with stage IIIA–IIIB lung SCC receiving definitive CCRT. Hospitalization for COPDAE within 1 year before CCRT is the significant independent risk factor for lung cancer death in the patients with stage IIIA–IIIB lung SCC receiving definitive CCRT. Abstract Background: To date, no data are available regarding the effect of chronic obstruction pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on survival in patients with lung squamous cell carcinoma (SCC) receiving definitive concurrent chemoradiotherapy (CCRT). Patients and methods: We enrolled 3986 patients with clinical stage IIIA–IIIB, unresectable lung SCC, who had received standard definitive CCRT, and categorized them into two groups based on their COPD status to compare overall survival outcomes. We also examined the effects of COPD severity (0, 1, or ≥2 hospitalizations for COPDA within 1 year before CCRT). Results: In the inverse probability of treatment weighting (IPTW)-adjusted model, the adjusted hazard ratio (aHR) (95% confidence interval (CI)) of all-cause death for COPD was 1.04 (1.01, 1.16), compared no COPD in patients with stage IIIA–IIIB lung SCC receiving definitive CCRT. In the IPTW-adjusted model, the aHRs (95% CIs) of 1 and ≥ 2 hospitalizations for COPDAE within 1 year before CCRT were 1.32 (1.19, 1.46) and 1.81 (1.49, 2.19) respectively, compared with no hospitalization for COPDAE. Conclusion: COPD and its severity are significant independent risk factors for all-cause death in patients with stage IIIA–IIIB lung SCC receiving definitive CCRT. Hospitalization for COPDAE within 1 year before CCRT is the significant independent risk factor for lung cancer death in the patients with stage IIIA–IIIB lung SCC receiving definitive CCRT.

Objectives Before launching large clinical trials to confirm the effects of statins in improving outcomes among men with prostate cancer (PC), the most appropriate target patient population and the type of statins need to be clearly identified. Patients and methods A retrospective cohort study was conducted using the Taiwan Cancer Registry of 2008–2014. This study included 5749 men with locally advanced and metastatic PC who received only androgen deprivation therapy (ADT) in the first year after their cancer diagnosis. Statin users were defined as anyone who was prescribed statins for >28 days. An inverse probability of treatment-weighted Cox model was used to estimate the effects of statin use on all-cause mortality and PC-specific mortality (PCSM) while treating the statin status as a time-dependent variable. Results Overall, 2259 patients died, and 1495 of them died of PC during a median follow-up of 3.6 years from 1 year after their diagnosis. Statin use was associated with significant reductions in all-cause mortality (hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.70–0.86) and PCSM (HR = 0.76, 95% CI: 0.68–0.86) for metastatic disease and all-cause mortality (HR = 0.66, 95% CI: 0.54–0.81) for locally advanced disease. Patients who received atorvastatin, pravastatin, rosuvastatin or pitavastatin showed a stronger reduction in mortality than those who received other statins. Benefits of statins were consistently observed in men who received post-diagnostic statins, even in those with high comorbidities or an old age. Conclusions Our results suggest that only atorvastatin, pravastatin and rosuvastatin were associated with improved survival in advanced PC patients receiving ADT.

Background/purpose: Recurrent aphthous stomatitis (RAS) is common and associated with certain comorbidities. The aim of this study was to investigate the prevalence of selected comorbidities in patients with RAUs and to compare the risks of comorbidity between the two cohorts of patients with or without RAUs based on the Taiwanese National Health Insurance Research Database. Methods: This case–control study included patients with recurrent aphthous stomatitis (the RAS cohort) and patients without recurrent aphthous stomatitis using 1:1 matching for year of index date, age, sex, monthly income, geographical location, and urbanization level (the non-RAS cohort). We calculated the prevalence of 31 medical comorbidities based on a modified version of the Elixhauser comorbidity index within 1 year before and after the index date. Conditional logistic regression was conducted to compare the risks of each comorbidity between the two cohorts. Results: Compared with the non-RAS cohort, the RAS cohort had a significantly higher prevalence of 16 comorbidities, with 2% or higher prevalence difference for hyperlipidemia (2.9%), headaches (6.9%), liver diseases (2.8%), and peptic ulcers (5.4%). The adjusted odds ratios were >1.5 for headaches (1.92), migraines (1.62), hypothyroidism (1.50), rheumatoid arthritis (1.92), ankylosing spondylitis (1.94), systemic lupus erythematosus (1.82), liver diseases (1.51), peptic ulcers (1.69), hepatitis (1.62), depression (1.76), and psychoses (1.50). Conclusion: Patients with recurrent aphthous stomatitis were associated with increased risk of specific comorbidities. Physicians should screen for these comorbidities for early detection and treatment. Keywords: Recurrent aphthous stomatitis, Comorbidities, Case–control cohort, Prevalence, Risk

Hsin-Hsien Yu,1,2 Yutaka Yonemura,3,4 Mao-Chih Hsieh,2,5 Chang-Yun Lu,2 Szu-Yuan Wu,6,7 Yan-Shen Shan1,8 1Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Peritoneal Dissemination Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan; 4Department of Surgery, Kusatsu General Hospital, Kusatsu, Shiga, Japan; 5Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 7Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan Objectives: The prognosis of ovarian teratoma with malignant transformation and peritoneal dissemination (PD) is poor. This condition is rare but associated with a high recurrence rate even after aggressive debulking surgery and adjuvant chemotherapy. In the present paper, we describe our experience of using cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for this condition. Methods: The data of ten female patients having ovarian teratoma with malignant transformation and PD between June 2007 and June 2017 were collected and reviewed retrospectively. CRS-HIPEC was performed according to the standard protocol. Patient characteristics, pathological reports, tumor markers, perioperative operative parameters, postoperative events, and disease status during the follow-up period were recorded. Results: The primary ovarian neoplasms were pure mature cystic teratoma with malignant transformation (n=6, including 5 of mucinous adenocarcinoma), mixed germ cell tumor with mature cystic teratoma and yolk sac tumor (YST) (n=1), pure immature teratoma (n=1), immature teratoma with growing teratoma syndrome (GTS) (n=1), and immature teratoma mixed YST with GTS (n=1). The mean levels of tumor markers, including carcinoembryonic antigen, cancer antigen 19-9 (CA19-9), and CA125, were markedly elevated. The recurrence rate was 10%. The median and mean disease-free survival (DFS) after CRS-HIPEC were 22.3 and 36.2 months, respectively, and the 5-year DFS rate is 88%. Conclusion: CRS-HIPEC is a safe therapeutic option for reducing the recurrence rate in selected patients with PD originating from ovarian teratoma with malignant transformation. Keywords: ovarian teratoma, malignant transformation, peritoneal dissemination, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy

Hsin-Hsien Yu,1–3 Mao-Chih Hsieh,2,3 Szu-Yuan Wu,4,5 Edgar D Sy,6 Yan-Shen Shan1,6 1Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 5Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan Background: Duodenal–jejunal bypass (DJB) is an important component of many types of current bariatric surgery including Roux-en-Y gastric bypass, mini-gastric bypass, biliopancreatic diversion, duodenal switch, and DJB plus sleeve gastrectomy. Surgery is often observed to ameliorate nonalcoholic steatohepatitis (NASH), but without a clearly delineated mechanism. In this study, we investigated the effects of DJB in diet-induced obese rats with NASH. Materials and methods: Male Wistar rats were divided into four groups and fed the following diets over 6 months: A) normal chow (NC group, n=6); B) methionine–choline-deficient (MCD)–high-fat (HF) diet (HF group, n=6); C) MCD–HF diet for 3 months followed by DJB and MCD–HF diet for subsequent 3 months (DJB group, n=6); and D) MCD–HF diet for 3 months followed by treatment with pioglitazone (PGZ) with MCD–HF diet for subsequent 3 months (PGZ group, n=6). Body weight, glucose tolerance, the homeostatic model assessment-insulin resistance index, and lipid profiles were compared. Liver and visceral adipose tissue histology, inflammatory marker and hepatic stellate cell (HSC) activity, and hepatocyte autophagy were assessed. Results: Compared with the HF group, the DJB group showed improved body weight, insulin sensitivity, lipid metabolism, and steatosis severity. The DJB group exhibited a significantly lower nonalcoholic fatty liver disease activity score than the HF and PGZ group (P

Purpose: To estimate long-term medical resource consumption in patients with subarachnoid aneurysmal hemorrhage (SAH) receiving surgical clipping or endovascular coiling. Patients and methods: From Taiwan’s National Health Insurance Research Database, we enrolled patients with aneurysmal SAH who received clipping or coiling. After propensity score matching and adjustment for confounders, a generalized linear mixed model was used to determine significant differences in the accumulative hospital stay (days), intensive care unit (ICU) stay, and total medical cost for aneurysmal SAH, as well as possible subsequent surgical complications and recurrence. Results: The matching process yielded a final cohort of 8102 patients (4051 and 4051 in endovascular coil embolization and surgical clipping, respectively) who were eligible for further analysis. The mean accumulative hospital stay significantly differed between coiling (31.2 days) and clipping (46.8 days, p &lt, 0.0001). After the generalized linear model adjustment of gamma distribution with a log link, compared with the surgical clipping procedure, the adjusted odds ratios (aOR, 95% confidence interval [CI]) of the medical cost of accumulative hospital stay for the endovascular coil embolization procedure was 0.63 (0.60, 0.66, 0·0001). The mean accumulative ICU stay significantly differed between the coiling and clipping groups (9.4 vs. 14.9 days, 0.0001). The aORs (95% CI) of the medical cost of accumulative ICU stay in the endovascular coil embolization group was 0.61 (0.58, 0.64, 0.0001). The aOR (95% CI) of the total medical cost of index hospitalization in the endovascular coil embolization group was 0·85 (0.82, 0.87, 0.0001). Conclusions: Medical resource consumption in the coiling group was lower than that in the clipping group.

Purpose: To estimate the oncologic outcomes of radical prostatectomy (RP) and high-dose intensity-modulated radiotherapy (IMRT) with short-term androgen-deprivation therapy (ADT) in relatively young men with unfavorable intermediate-risk prostate cancer, as defined by the National Comprehensive Cancer Network (NCCN-UIR-PC). Patients and Methods: We enrolled relatively young men (≤65 years) from the Taiwan Cancer Registry who had been diagnosed as having NCCN-UIR-PC and who had received RP or high-dose IMRT (at least ≥72 Gy) with short-term ADT (4–6 months). After propensity score matching of the confounders, Cox proportional regression was used to model the time from the index date (i.e., date of diagnosis) to all-cause death, biochemical failure (BF), locoregional recurrence (LRR), and distant metastasis (DM). Results: The corresponding adjusted hazard ratios (95% confidence intervals) of the risk of all-cause death, BF, LRR, and DM were 2.76 (1.36–5.60, p = 0.0050), 2.74 (1.72–4.84, p &lt, 0.0001), 1.28 (1.09–1.90, p = 0.0324), and 2.11 (1.40–4.88, p = 0.0052), respectively. Conclusions: RP is superior to high-dose IMRT with short-term ADT in terms of oncologic outcomes for relatively young men with UIR-PC.

Alopecia areata (AA) is an autoimmune disease that causes sudden hair loss. Although few studies have reported the association between AA and attention-deficit/hyperactivity disorder (ADHD), the impact of methylphenidate (MPH) on AA has not been examined. This study examined whether AA risk is higher in children with ADHD than in those without ADHD as well as the impact of MPH use on AA risk in children with ADHD. From the Taiwan Maternal and Child Health Database, we enrolled all 1,750,456 newborns from 2004 to 2017 in Taiwan. Of them, 90,016 children received a diagnosis of ADHD whereas the remaining 1,660,440 did not. To compare AA risk in ADHD and the impact of MPH treatment on it, multiple Cox regression with adjustments for covariates (i.e., age, sex, and psychiatric comorbidities) was performed. The results indicated that 88 (0.098%) children with ADHD and 1191 (0.072%) children without ADHD had AA. Nevertheless, after adjustment for the covariates, AA risk was higher in children with ADHD than in those without ADHD (adjusted hazard ratio [aHR]: 1.30, 95% confidence interval [CI]: 1.04–1.64). Our data indicated a considerable reduction in AA risk (aHR: 0.64) among children with ADHD who received MPH than among those who did not receive MPH, however, this difference was nonsignificant, indicated by a wide 95% CI (0.32–1.25). In conclusion, ADHD and AA may share some underlying mechanisms.

Purpose: To estimate the rates of positive surgical margin (PSM) and biochemical failure&ndash, free survival (BFS) among patients with prostate cancer (PC) receiving open, laparoscopic, or robotic radical prostatectomy (RP). Patients and Methods: The patients were men enrolled in the Taiwan Cancer Registry diagnosed as having PC without distant metastasis who received RP. After adjustment for confounders, logistic regression was used to model the risk of PSM following RP. After adjustment for confounders, Cox proportional regression was used to model the time from the index (i.e., surgical) date to biochemical recurrence. Results: The adjusted odds ratios (95% CIs) of PSM risk after propensity score adjustment for laparoscopic versus open, robotic versus open, and robotic versus laparoscopic RP 95% CIs were 1.25 (0.88 to 1.77, p = 0.2064), 1.16 (0.88 to 1.53, p = 0.2847), and 0.93 (0.70 to 1.24, p = 0.6185), respectively. The corresponding adjusted hazard ratios (95% CIs) of risk of biochemical failure after propensity score adjustment were 1.16 (0.93 to 1.47, p = 0.1940), 1.10 (0.83 to 1.47, p = 0.5085), and 0.95 (0.74 to 1.21, p = 0.6582). Conclusions: No significant differences in PSM or BFS were observed among patients receiving open, laparoscopic, or robotic RP.

PURPOSE: To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in patients with breast invasive ductal carcinoma (IDC) receiving neoadjuvant chemotherapy (NACT) followed by breast-conserving surgery (BCS), we obtained pathologic response rates (PRRs) for combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) from clinical and pathologic reports, and we used these as predictors.PATIENTS AND METHODS: We enrolled patients with IDC who had received NACT followed by BCS. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) for the patients’ PRRs; other independent predictors were controlled for or stratified in the analysis.RESULTS: We analyzed 1047 patients with IDC (611, 260, and 176 patients in clinical stages IIB, IIIA, and IIIB-C, respectively) receiving NACT and BCS. After multivariate Cox regression analyses, the adjusted HRs (aHRs; 95% CI) in patients with pathologic complete response (ypT0N0) were 0.26 (0.13–0.56), 0.36 (0.15–0.85), and 0.15 (0.08–0.31) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with downstaging of AJCC stages were 0.55 (0.35–0.89), 0.91 (0.62–0.96), and 0.63 (0.43–0.91) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with upstaging of AJCC stages were 1.77 (1.06–2.24), 1.08 (1.03–1.82), and 1.19 (1.07–2.01) for all-cause mortality, LRR, and DM, respectively.CONCLUSION: The impacts of AJCC-stage PRRs are useful predictive tools and strong predictors for OS, LRR, and DM in patients with breast IDC receiving NACT followed by BCS.

Purpose To assess the feasibility and short-term outcomes of neoadjuvant chemoradiotherapy (CCRT) followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery (TaTME-SPLS) for low-lying rectal adenocarcinoma. Methods and materials A total of 23 patients with clinical stage II-III low-lying (from anal verge 0-8 cm) rectal adenocarcinoma who underwent neoadjuvant CCRT followed by TaTME-SPLS consecutively from December 2015 to December 2018, were enrolled into our study. Chi-squared testing and Student’s t testing were used to make parametric comparisons, and Fisher’s exact test or the Mann–Whitney U test were used to make nonparametric comparisons. Results Conversion rate in patients who underwent neoadjuvant CCRT followed by TaTME-SPLS was only 4%. The mean operation time was 366 min and the inter-sphincter resection (ISR) was done for 14 patients (60%). The mean number of lymph nodes harvested was 15. There was no surgical mortality, but the 30-day morbidity rate was 21% (5 patients were Clavien-Dindo I-II). Pathological complete response was 21.74% with 100% organ preservation and 100% clear distal margin after neoadjuvant CCRT followed by TaTME-SPLS. Conclusion TaTME-SPLS would be highly successful in lymph node negative and low T stage of low-lying rectal cancer patients who had pathological complete remission or high percentage of partial remission after neoadjuvant CCRT.

Although patients aged70 years are subject to early oral cavity squamous cell carcinoma (E-OCSCC), evidence is currently lacking regarding the probable outcomes of definitive radiotherapy (RT) compared to surgery in this population.We recruited patients aged ≥70 years with a diagnosis of E-OCSCC from the Taiwan Cancer Registry Database. Propensity score matching was performed, and Cox proportional-hazards model curves were used to analyze all-cause mortality of patients at different age intervals undergoing different treatments.The matching process yielded a final cohort of 604 patients in the definitive RT and surgery cohorts who were eligible for further analysis. These patients were classified as old (70-80 years) and very old (80 years). In the multivariate Cox regression analysis, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) for surgery compared with definitive RT was 0.465 (0.354-0.610, P 0.001). The aHR (95% CI) for age80 years compared with age 70-80 years was 2.370 (1.720, 3.265, P 0.001). The aHR (95% CI) for T2N0M0 compared with T1N0M0 was 1.752 (1.321-2.32, P 0.001). The aHR (95% CI) for Charlson Comorbidity Index (CCI) ≥ 2 compared with CCI = 0 was 1.264 (1.137-1.738, P = 0.011). After stratified analysis, the aHRs for surgery compared with definitive RT were 0.484 (0.352-0.665, P 0.001) and 0.411 (0.232-0.728, P = 0.002) among old and very old patients with E-OCSCC, respectively.Surgery may be more beneficial than definitive RT in selected elderly patients with E-OCSCC.

There is currently no system to predict 90-day morality among patients with locally advanced head and neck squamous cell carcinoma (HNSCC) after the completion of concurrent chemoradiotherapy (CCRT).To validate the accuracy of a predictive scoring system for 90-day mortality among patients with locally advanced HNSCC who have completed CCRT.This prognostic study included 16 029 patients with HNSCC who completed CCRT between January 2006 and December 2015. Data were extracted from the Taiwan Cancer Registry Database. A risk scoring system was developed based on significant risk factors and corresponding risk coefficients. Data analysis was conducted from June 2018 to February 2019.Mortality within 90 days of completion of definitive CCRT.The 90-day mortality rate after completion of CCRT and the accuracy of the scoring system, based on a comparison of mortality rates between training and test data sets.Among 16 029 patients with locally advanced HNSCC, 1068 (6.66%; 1016 [95.1%] men; mean [SD] age, 55.11 [11.45] years) died before reaching the 90-day threshold, and 14 961 (93.4%; 14 080 [94.1%] men; mean [SD] age, 52.07 [9.99] years) survived. Multivariable analysis revealed that being aged 50 years or older (adjusted hazard ratio [aHR], 1.263; 95% CI, 1.104-1.445; P .001), being aged 70 years or older (aHR, 2.183; 95% CI, 1.801-2.645; P .001), having pneumonia (aHR, 1.946; 95% CI, 1.636-2.314; P .001), having sepsis (aHR, 3.005; 95% CI, 2.503-3.607; P .001), having hemiplegia (aHR, 1.430; 95% CI, 1.085-1.884; P = .01), having moderate or severe renal disease (aHR, 2.054; 95% CI, 1.643-2.568; P .001), having leukemia (aHR, 4.541; 95% CI, 1.132-8.207; P = .03), and having non-HNSCC metastatic solid cancers (aHR, 1.457; 95% CI, 1.292-1.644; P .001) were significant risk factors for 90-day mortality. Risk scores were categorized as very low risk (score of 0), low risk (score 1-3), moderate risk (score 4-6), and high risk (score ≥7), with 90-day mortality rates of 3.37%, 5.00% to 10.98%, 16.15% to 29.13%, and 33.93% to 37.50%, respectively. Mortality rates for patients with the same risk score in the training and test data sets were similar (score of 0, 3.27% vs 3.66%; score of 6, 27.42% vs 25.00%).In this prognostic study, a 90-day mortality scoring system accurately predicted 90-day mortality among patients with locally advanced HNSCC who completed CCRT.

Purpose: The effects of influenza vaccines are unclear for elderly individuals with disabilities. We use a population-based cohort study to estimate the effects of influenza vaccines in elderly individuals with and without disabilities. Methods: Data were taken from the National Health Insurance Research Database and Disabled Population Profile of Taiwan. A total of 2,741,403 adults aged 65 or older were identified and 394,490 were people with a disability. These two groups were further divided into those who had or had not received an influenza vaccine. Generalized estimating equations (GEE) were used to compare the relative risks (RRs) of death and hospitalization across the four groups. Results: 30.78% elderly individuals without a disability and 34.59% elderly individuals with a disability had vaccinated for influenza. Compared to the unvaccinated elderly without a disability, the vaccinated elderly without a disability had significantly lower risks in all-cause mortality (RR = 0.64) and hospitalization for any of the influenza-related diseases (RR = 0.91). Both the unvaccinated and vaccinated elderly with a disability had significantly higher risks in all-cause mortality (RR = 1.81 and 1.18, respectively) and hospitalization for any of the influenza-related diseases (RR = 1.73 and 1.59, respectively). Conclusions: The elderly with a disability had higher risks in mortality and hospitalization than those without a disability, however, receiving influenza vaccinations could still generate more protection to the disabled elderly.

Predicting the number of new suspected or confirmed cases of novel coronavirus disease 2019 (COVID-19) is crucial in the prevention and control of the COVID-19 outbreak. Social media search indexes (SMSI) for dry cough, fever, chest distress, coronavirus, and pneumonia were collected from 31 December 2019 to 9 February 2020. The new suspected cases of COVID-19 data were collected from 20 January 2020 to 9 February 2020. We used the lagged series of SMSI to predict new suspected COVID-19 case numbers during this period. To avoid overfitting, five methods, namely subset selection, forward selection, lasso regression, ridge regression, and elastic net, were used to estimate coefficients. We selected the optimal method to predict new suspected COVID-19 case numbers from 20 January 2020 to 9 February 2020. We further validated the optimal method for new confirmed cases of COVID-19 from 31 December 2019 to 17 February 2020. The new suspected COVID-19 case numbers correlated significantly with the lagged series of SMSI. SMSI could be detected 6&ndash, 9 days earlier than new suspected cases of COVID-19. The optimal method was the subset selection method, which had the lowest estimation error and a moderate number of predictors. The subset selection method also significantly correlated with the new confirmed COVID-19 cases after validation. SMSI findings on lag day 10 were significantly correlated with new confirmed COVID-19 cases. SMSI could be a significant predictor of the number of COVID-19 infections. SMSI could be an effective early predictor, which would enable governments&rsquo, health departments to locate potential and high-risk outbreak areas.

Objectives: To analyze the association of the use of different doses of angiotensin II receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) independently with lung cancer risk and to evaluate the lung cancer type that may be related to ARB or ACEI use. Patients and Methods: A nationwide population-based nested case–control study was conducted using Taiwan National Health Insurance Research Database linked to the Taiwan Cancer Registry database between January 1, 2000, and December 31, 2016. The cumulative defined daily dose (DDD) was estimated. We divided all users of ACEI or ARB into three categories based on the DDD of ACEI or ARB: low dose, middle dose, and high dose. Results: We identified 16,091 patients with newly diagnosed lung cancer, and 80,455 controls with hypertension were selected. Univariate and multivariate conditional logistic regressions showed that the independent risk factor for lung cancer was high-dose (≥1095 DDD) ARB use (adjusted odds ratio [OR]: 1.069, 95% confidence interval [CI]: 1.02–1.12, P = 0.003). An increase in lung adenocarcinoma (ADC) risk was associated with middle-dose (adjusted OR: 1.073, 95% CI: 1.01–1.14, P = 0.025) to high-dose (adjusted OR: 1.106, 95% CI: 1.05–1.17, P < 0.001) ARB use and high-dose ACEI use (adjusted OR: 1.095, 95% CI: 1.01–1.19, P = 0.033). No association was observed between different ARB or ACEI dose levels and the risk of lung squamous cell carcinoma and small-cell lung carcinoma. Conclusions: Our results suggest that the use of both ACEI and ARB at a high cumulative dose is associated with the risk of lung ADC. Funding Statement: Taipei Medical University and Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital (Funding Number 10908 & 10909). Declaration of Interests: The authors have no potential conflicts of interest to declare. Ethics Approval Statement: Our protocols were reviewed and approved by the Institutional Review Board of Taipei Medical University (TMU-JIRB No. 201712019).

Purpose: To estimate the survival effects of contemporary external beam radiotherapy (EBRT) boost modalities (intensity-modulated radiation therapy or volumetric modulated arc therapy) and high dose-rate brachytherapy (HDR-BT) boost in patients with cervical cancer (CC). Patients and Methods: Patients who had been diagnosed as having CC were recruited from the Taiwan Cancer Registry Database. Propensity score matching was performed, and Cox proportional-hazards model curves were used to analyze the all-cause mortality of patients who received standard whole-pelvis irradiation with different boost modalities. Results: The matching process yielded a final cohort of 1,630 patients (815 in the EBRT boost and HDR-BT boost groups, respectively) eligible for further analysis. The multivariate Cox regression analyses indicated that the adjusted hazard ratio (95% confidence intervals) for EBRT boost compared with HDR-BT boost was 1.62 (1.43–1.84). Multivariable analysis revealed that the independent poor prognostic factors of all-cause mortality among patients with CC were adenocarcinoma, no chemotherapy, EBRT boost, Charlson comorbidity index score ≥ 1, age ≥ 60 years, and advanced International Federation of Gynecology and Obstetrics stage. Conclusions: HDR-BT boost may be more beneficial than contemporary EBRT boost in selected patients with CC. Funding Statement: Lo-Hsu Medical Foundation, LotungPoh-Ai Hospital, supports Szu- Yuan Wu’s work (Funding Number: 10908 and 10909). Declaration of Interests: The authors have no potential conflicts of interest to declare. Ethics Approval Statement: Our protocols were reviewed and approved by the Institutional Review Board of Taipei Medical University (TMU-JIRB No. 201702019).

PURPOSE: To estimate the outcomes of definitive concurrent chemoradiotherapy (CCRT) for bulky or advanced-stage cervical squamous cell carcinoma (SCC) and adenocarcinoma (ADC). PATIENTS AND METHODS: We enrolled patients who had been diagnosed as having cervical SCC or ADC and received definitive CCRT between January 1, 2007, and December 31, 2015. A Cox regression analysis was performed to determine the hazard ratio (HR) and 95% confidence intervals (95% CI); independent predictors were stratified or controlled for in the analysis, and the endpoint was all-cause mortality among patients with cervical SCC and ADC who received CCRT. Propensity score matching was performed to create well-balanced groups. RESULTS: We enrolled 3258 patients who had International Federation of Gynecology and Obstetrics (FIGO) stage IB2–IVA cervical cancer without distant metastasis. Among them, 2927 patients with cervical SCC and 331 patients with cervical ADC received definitive CCRT. The results of multivariate Cox regression analysis indicated that ADC, advanced FIGO stage, no intracavitary brachytherapy, old age, earlier year of diagnosis, and higher comorbidity scores were significant independent poor prognostic factors of all-cause mortality in patients with cervical cancer who received definitive CCRT. Patients with cervical ADC who received definitive CCRT had higher all-cause mortality, locoregional recurrence (LRR), and distant metastasis (DM) (adjusted HR [95% CI]: 2.10 [1.79–2.46], 1.79 [1.35–2.37], and 1.97 [1.54–2.53] for all-cause mortality, LRR, and DM, respectively) compared with patients with cervical SCC who received CCRT. CONCLUSION: Definitive CCRT in patients with cervical ADC resulted in lower overall survival, higher LRR, and higher DM rate compared with patients with cervical SCC. Funding Statement: Lo-Hsu Medical Foundation, LotungPoh-Ai Hospital, supports SzuYuan Wu’s work (Funding Number: 10908 and 10909). Declaration of Interests: The authors have no potential conflicts of interest to declare. Ethics Approval Statement: Our protocols were reviewed and approved by the Institutional Review Board of Taipei Medical University (TMU-JIRB No. 201712019).

Background: To estimate the predictive factors in anesthesiologists be infected of COVID-19 from endotracheal intubation for COVID-19 confirmed patients br br

Purpose: To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in breast invasive ductal carcinoma (IDC) patients receiving neoadjuvant chemotherapy (NACT) and total mastectomy (TM), we used the degree of pathologic response (DPR) of primary breast diseases (T stages), nodal diseases (N stages), and combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) based on existing clinical and pathologic reports as predictors. Patients and Methods: We enrolled patients with IDC who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) of DPR; other independent predictors were controlled for or stratified in the analysis. Results: We analyzed 3654 IDC patients (1031, 1215, 1003, and 405 patients with clinical stages IIB, IIIA, IIIB, and IIIC, respectively) receiving NACT and TM. After multivariate Cox regression analyses, the adjusted HRs (aHRs) (95% CI) for all-cause mortality, LRR, and DM were noted to be 0.21 (0.13–0.34), 0.19 (0.08–0.48), and 0.33 (0.23–0.47), respectively, for pCR; 0.56 (0.48–0.65), 0.67 (0.51–0.89), and 0.61 (0.52–0.70), respectively, for AJCC downstaging; and 1.85 (1.56–2.18), 1.17 (0.84–1.62), and 1.61 (1.36–1.90), respectively, for AJCC upstaging. Conclusion: The DPR parameters used in the study are easily applied because they are based on existing staging records, and they can strongly predict OS, LRR, and DM in IDC patients receiving NACT and TM, regardless of clinical stage. The results can be used to guide adjuvant treatment. Funding Statement: Lo-Hsu Medical Foundation, LotungPoh-Ai Hospital, supports SzuYuan Wu’s work (Funding Number: 10908 and 10909). Declaration of Interests: The authors have no potential conflicts of interest to declare. Ethics Approval Statement: Our protocols were reviewed and approved by the Institutional Review Board of Taipei Medical University (TMU-JIRB No. 201712019).

Purpose Large-scale, prospective, randomized studies of the efficacy of thoracic radiotherapy (RT) in patients with unresectable stage IIIB–IV epidermal growth factor receptor (EGFR)-mutant lung adenocarcinomas who received and responded to EGFR tyrosine kinase inhibitor (TKI) treatment are not currently available. Therefore, we designed a propensity score-matched, nationwide, population-based, cohort study for estimating the effects of thoracic RT on patients with EGFR-mutant lung adenocarcinomas. Patients and methods We analyzed patients with unresectable stage IIIB–IV EGFR mutant lung adenocarcinomas and categorized them into two groups according to treatment modality and compared their outcomes; groups 1 and 2 consisted of patients who received EGFR TKI treatment alone until tumor progression and those who received and responded to EGFR TKI treatment and subsequently received thoracic RT for lung tumors, respectively. The patients in groups 2 and 1 were matched at a ratio of 1:4. Results The matching process yielded a final cohort of 1475 patients (1180 and 295 patients in groups 1 and 2, respectively) who were eligible for further analysis. According to both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) derived for thoracic RT for lung tumor after EGFR TKI use and tumor response (group 2) compared with EGFR TKI treatment alone (group 1) was 0.72 (0.60–0.85). Conclusions Thoracic RT might be associated with overall survival in patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinomas who received and responded to EGFR TKI treatment.

Background No large-scale, head-to-head, phase III, randomized, controlled trial with an adequate sample size has investigated the effect of concurrent low-dose (LD) or high-dose (HD) cisplatin with radiotherapy on nasopharyngeal cancer (NPC). Thus, we conducted a propensity-score-matched, nationwide, population-based cohort study in Taiwan to investigate the outcomes of LD-concurrent chemoradiotherapy (CCRT) or HD-CCRT with intensity-modulated radiotherapy (IMRT) in patients with advanced NPC. Methods In this study, patients were categorized into 2 groups according to their chemotherapy regimen: HD-CCRT and LD-CCRT groups. Results We enrolled 1968 patients (328 and 1640 in the LD-CCRT and HD-CCRT groups, respectively) who had received CCRT with IMRT. According to both univariate and multivariate Cox regression analyses, a hazard ratio (95% confidence interval) of 0.75 (0.54–1.06, P = .103) was derived for the HD-CCRT group. Conclusion LD-CCRT or HD-CCRT with IMRT can be a standard treatment that can prolong the survival of patients with advanced NPC.

Background Recurrent aphthous stomatitis (RAS) is considered a prophase symptom in patients with specific cancers. This study assessed the association between RAS and subsequent onset of cancer based on a nationwide population‐based database in Taiwan. Materials and Methods We selected study participants from the National Health Insurance Research Database from January 2000 to December 2008. Patients in the non‐RAS cohort were matched to case study patients at a 1:1 ratio through frequency matching. All participants were followed up for at least 5 years, and those who received cancer diagnoses during follow‐up were identified. Results Among 52 307 patients with and 52 304 patients without RAS, the combined hazard ratio (HR) of all subsequent cancer cases was 1.3 (95% confidence interval [CI]: 1.25‐1.35, P = 0). RAS diagnosis was associated with risk for cancers of the head and neck (aHR = 2, 95% CI: 1.8‐2.3), colon (aHR = 1.2, 95% CI: 1.1‐1.4), liver (aHR = 1.1, 95% CI: 1‐1.3), pancreas (aHR = 1.4, 95% CI: 1.1‐1.7), skin (aHR = 1.4, 95% CI: 1.2‐1.7), breast (aHR = 1.2, 95% CI: 1.1‐1.4), and prostate (aHR = 1.5, 95% CI: 1.3‐1.8), as well as hematologic cancers (aHR = 1.6, 95% CI: 1.3‐1.9). A higher risk was observed for male patients (aHR = 1.35, 95% CI: 1.28‐1.42) than for female patients (aHR = 1.25, 95% CI: 1.18‐1.31) with RAS. Conclusions RAS was associated with specific cancers. Susceptible RAS patients should be screened for specific cancers.

In the era of intensity modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of adjuvant therapies such as adjuvant concurrent chemoradiotherapy (CCRT), adjuvant sequential chemotherapy and radiotherapy (CT‐RT), and adjuvant CT alone in resectable pancreatic adenocarcinoma (PA). Through propensity score matching, we designed a nationwide, population‐based, head‐to‐head cohort study to determine the effects of dissimilar adjuvant treatments on resectable PA. We minimized the confounding of various adjuvant treatment outcomes among the following resectable PA groups of patients from the Taiwan Cancer Registry database: group 1, adjuvant CCRT; group 2, adjuvant sequential CT‐RT; and group 3, adjuvant CT alone. All the studied techniques are IMRTs. The matching process yielded a final cohort of 588 patients (196, 196, and 196 patients in groups 1, 2, and 3, respectively). In both univariate and multivariate Cox regression analyses, adjusted hazard ratios (aHRs; 95% confidence interval [CI]) of death derived for the adjuvant CCRT and adjuvant sequential CT‐RT cohorts compared with the adjuvant CT alone cohort were 0.398 (0.314–0.504) and 0.307 (0.235–0.402), respectively. A combination of adjuvant IMRT and CT for resectable PA treatment improves survival to a greater extent than does adjuvant CT alone.

Background and Objectives: To evaluate the predictive factor for and patterns of distant metastasis in patients with rectal adenocarcinoma receiving total mesorectal excision (TME). Methods: We enrolled 217 consecutive patients who had histologically confirmed rectal adenocarcinoma and underwent surgery at Taipei Medical University- Wanfang Hospital between January 2000 and December 2014. TME was performed in all patients undergoing a sphincter-sparing procedure or abdominal perineal resection of rectal cancer. We performed univariate and multivariate Cox regression analyses of the distant metastasis rate in all patients to evaluate predictive factors. Overall survival (OS) rates were calculated using the Kaplan-Meier method, and Kaplan-Meier survival curves were compared using the log-rank test. Results: A multivariate Cox regression analysis of the distant metastasis rate in patients with rectal adenocarcinoma identified tumor locations and American Joint Committee on Cancer (AJCC) stages as prognostic risk factors. The adjusted hazard ratios (aHRs) of distant metastasis for the upper-third, middle-third, and AJCC stage I-II cancers were 0.08 (95% CI, 0.01-0.69; p = 0.021), 0.41 (95% CI, 0.15-0.99; p = 0.047), and 0.20 (95% CI, 0.10-0.66; p = 0.008), respectively. The 5-year lung metastasis rates among patients with upper-, middle-, and lower-third rectal cancers were 0%, 3.37%, and 13.33%, respectively (log-rank, p = 0.001), and the 5-year liver metastasis rates among patients with upper-, middle-, and lower-third rectal cancers were 2.12%, 9.10%, and 11.76%, respectively (log-rank, p = 0.096). The 5-year OS rates also differed with different rectal adenocarcinoma locations. The 5-year OS rates for upper, middle, and lower rectal cancers were 96%, 86%, and 64%, respectively (log-rank, p < 0.001). Conclusion: A poor OS rate and high lung or liver metastasis rate were observed in distal rectal adenocarcinoma. Longer intensive surveillance of the chest, abdomen, and pelvis after TME in distal rectal adenocarcinoma could be necessary.

Simple Summary That the definitive optimal treatments for relatively young men (aged ≤ 65 years) with high- or very high-risk localized prostate cancer (HR/VHR-LPC) are radical prostatectomy (RP) or radiation plus antiandrogen therapy (RT-ADT) is controversial. To the best of our knowledge, our study is the first and largest to examine biochemical failure (BF), all-cause death, locoregional recurrence, and distant metastasis in relatively young men with HR/VHR-LPC as defined by National Comprehensive Cancer Network risk strata. After head-to-head propensity score matching was used to balance the potential confounders, a multivariable Cox proportional hazards regression model was used to analyze oncologic outcomes. In relatively young men with HR/VHR-LPC, RP and RT-ADT yielded similar oncologic outcomes and RP reduced the risk of BF compared with RT-ADT. Abstract That intensity-modulated radiotherapy (IMRT) plus antiandrogen therapy (IMRT-ADT) and radical prostatectomy (RP) are the definitive optimal treatments for relatively young patients (aged ≤ 65 years) with high- or very high-risk localized prostate cancer (HR/VHR-LPC), but remains controversial. We conducted a national population-based cohort study by using propensity score matching (PSM) to evaluate the clinical outcomes of RP and IMRT-ADT in relatively young patients with HR/VHR-LPC. Methods: We used the Taiwan Cancer Registry database to evaluate clinical outcomes in relatively young (aged ≤ 65 years) patients with HR/VHR-LPC, as defined by the National Comprehensive Cancer Network risk strata. The patients had received RP or IMRT-ADT (high-dose, ≥72 Gy plus long-term, 1.5–3 years, ADT). Head-to-head PSM was used to balance potential confounders. A Cox proportional hazards regression model was used to analyze oncologic outcomes. Results: High-dose IMRT-ADT had a higher risk of biochemical failure (adjusted hazard ratio [aHR] = 2.03, 95% confidence interval [CI] 1.56–2.65, p < 0.0001) compared with RP; IMRT-ADT did not have an increased risk of all-cause death (aHR = 1.2, 95% CI 0.65–2.24, p = 0.564), locoregional recurrence (aHR = 0.88, 95% CI 0.67–1.06, p = 0.3524), or distant metastasis (aHR = 1.03, 95% CI 0.56–1.9, p = 0.9176) compared with RP. Conclusion: In relatively young patients with HR/VHR-LPC, RP and IMRT-ADT yielded similar oncologic outcomes and RP reduced the risk of biochemical failure compared with IMRT-ADT.

Scarce evidence is available in Asia for estimating the long-term risk and prognostic factors of major complications such as re-rupture, vasospasm, or re-stroke for patients with aneurysmal subarachnoid hemorrhage (SAH) undergoing endovascular coil embolization or surgical clipping. This is the first head-to-head propensity score-matched study in an Asian population to demonstrate that endovascular coil embolization for aneurysmal SAH treatment is riskier than surgical clipping in terms of re-rupture, vasospasm, or re-stroke. In addition, the independent poor prognostic factors of vasospasm or re-stroke were endovascular coil embolization, male sex, older age (≥65 years, the risk of vasospasm increases with age), hypertension, congestive heart failure, diabetes, previous transient ischemic attack, or stroke in aneurysmal SAH treatment. Background: To estimate the long-term complications and prognostic factors of endovascular coil embolization or surgical clipping for patients with ruptured aneurysmal subarachnoid hemorrhage (SAH). Methods: We selected patients diagnosed with aneurysmal SAH between 1 January 2011 and 31 December 2017. Propensity score matching was performed, and Cox proportional hazards model curves were used to analyze the risk of re-rupture, vasospasm, and re-stroke in patients undergoing the different treatments. Findings: Multivariate Cox regression analysis revealed that the adjusted hazard ratio (aHR) of re-rupture for endovascular coil embolization compared with surgical clipping was 1.36 (95% confidence interval [CI]: 1.17–1.57, p &lt, 0.0001). The aHRs of the secondary endpoints of vasospasm and re-stroke (delayed cerebral ischemia) for endovascular coil embolization compared with surgical clipping were 1.14 (1.02–1.27, p = 0.0214) and 2.04 (1.83–2.29, 0.0001), respectively. The independent poor prognostic factors for vasospasm and re-stroke were endovascular coil embolization, male sex, older age (≥65 years, risk increases with age), hypertension, congestive heart failure, diabetes, and previous transient ischemic attack or stroke. Interpretation: Endovascular coil embolization for aneurysmal SAH carries a higher risk than surgical clipping of both short- and long-term complications including re-rupture, vasospasm, and re-stroke.

Purpose We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving breast conservative surgery (BCS) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints. Patients and methods Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.67 (0.46–0.99) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3–4, pathological nodal (pN) stage 2–3, and Her-2 positivity were 1.87 (1.03–3.42), 2.31 (1.20–4.44), 1.67 (1.09–2.56), 2.43 (1.18–4.97), 1.17 (1.03–1.19), 1.28 (1.13–2.24), 1.20 (1.05–2.22), and 1.59 (1.01–2.51), respectively, compared with those for differentiation grade I, clinical stage I, pT1, pN0, and HER-2 negativity. The aHR of LRR for adjuvant radiotherapy was 0.60 (0.38–0.97) compared with that for no adjuvant radiotherapy. Conclusion PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with INHA-GA without propofol.

PURPOSE: The survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on patients with muscle-invasive bladder urothelial carcinoma (MIBUC) receiving concurrent chemoradiotherapy (CCRT) for bladder preservation is unclear. METHODS: We recruited patients with MIBUC, clinical stages IIA–IVB, who had received maximal transurethral resection of bladder tumor (TURBT) followed by CCRT from the Taiwan Cancer Registry Database. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into two groups by using propensity score matching based on the preexisting COPD status (within 1 year before CCRT) to compare overall survival outcomes: Group 1 (never smokers without COPD) and Group 2 (current smokers with COPD). RESULTS: In multivariate Cox regression analyses, the adjusted hazard ratio (aHR, 95% confidence interval (CI)) of all-cause mortality in Group 2 compared with Group 1 was 1.89 (1.12–3.18), p = 0.017. The aHRs (95% CIs) of all-cause mortality for ≥1 and ≥2 hospitalizations for COPDAE within 1 year before CCRT for bladder preservation were 3.26 (1.95–5.46) and 6.33 (3.55–11.281) compared with non-COPDAE patients with MIBUC undergoing CCRT for bladder preservation. CONCLUSIONS: Among patients with MIBUC undergoing TURBT followed by CCRT for bladder preservation, current smokers with smoking-related COPD had worse survival outcomes than did nonsmokers without COPD. Condensed Abstract: This was the first study to estimate the survival impact of smoking-related chronic obstructive pulmonary disease (COPD) on patients with muscle-invasive bladder urothelial carcinoma (MIBUC) receiving maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy (CCRT) for bladder preservation. Smoking-related COPD was a significant independent risk factor for all-cause mortality in patients with clinical stages IIA–IVB receiving TURBT followed by CCRT. Hospitalization frequency for COPD with at least one acute exacerbation within 1 year before CCRT was highly associated with high mortality for patients with MIBUC receiving CCRT for bladder preservation. Not only all-cause death but also bladder cancer death and COPD death were significantly higher in the current-smoking COPD group than in the never-smoking non-COPD group.

Importance Few studies have evaluated long-term surgical complications in patients with prostate cancer (PC) who receive open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP), or robot-assisted radical prostatectomy (RARP). Objective To examine the perioperative and postoperative surgical complications among patients with PC who underwent ORP, LRP, or RARP. Design, Setting, and Participants This cohort study included patients who received a diagnosis of resectable PC and underwent RP between January 1 and December 31, 2015. Participants were enrolled in the Taiwan Cancer Registry. The index date was the date of surgery, and the follow-up duration was the period from the index date to December 31, 2018. Data analysis was performed in September 2020. Exposures ORP, LRP, or RARP. Main Outcomes and Measures Two multivariate mixed models accounting for hospital clusters were fitted to ascertain the association of RARP with treatment outcomes (ie, hospital stay, blood transfusion, postoperative pain, erectile dysfunction, urinary incontinence, and hernia); general linear regression models were used for continuous outcomes, the amount of blood transfused, and hospital stay, and logistic regression models were used for analyzing postoperative outcomes and surgical complications. Results Of the 1407 patients included in this study, 315 (22.4%) received ORP (mean [SD] age, 66.4 [6.8] years), 276 (19.6%) received LRP (mean [SD] age, 66.8 [6.4] years), and 816 (58.0%) received RARP (mean [SD] age, 66.1 [6.7] years). Mean (SD) follow-up in the full cohort was 36.7 (4.6) months. No statistically significant differences were observed in age, clinical tumor stage, pathological tumor stage, Gleason score, Gleason grade group, preoperative prostate-specific antigen concentration, D'Amico risk classification, and hospital level. A shorter hospital stay was observed for patients undergoing RARP vs those undergoing ORP (mean [SE] difference, -1.64 [0.22] days; P

Purpose: the survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with invasive ductal carcinoma (IDC) receiving standard treatments. Methods: we recruited women with clinical stage I–III IDC from the Taiwan Cancer Registry Database who had received standard treatments between 1 January 2009 and 31 December 2018. The time-dependent Cox proportional hazards model was used to analyze all-cause mortality. To reduce the effects of potential confounders when all-cause mortality between Groups 1 and 2 were compared, 1:2 propensity score matching (PSM) was performed. We categorized the patients into two groups based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD group). Results: PSM yielded 2319 patients with stage I–III IDC (773 and 1546 in Groups 1 and 2, respectively) eligible for further analysis. In the multivariate time-dependent Cox regression analyses, the adjusted hazard ratio (aHR, 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.04 (0.83–1.22). The aHRs (95% CIs) of all-cause mortality for ≥1 hospitalization for COPDAE within one year before breast surgery was 1.51 (1.18–2.36) compared with no COPDAE. Conclusion: smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I–III IDC receiving standard treatments. Being hospitalized at least once for COPDAE within one year before breast surgery is highly associated with high mortality for women with IDC receiving standard treatments. The severity of smoking-related COPD before treatments for breast cancer might be an important prognostic factor of survival. Thus, the information of the severity of COPD before treatment for breast cancer might be valuable for increasing the survival rate in treatment of breast cancer, especially in the prevention of progress from COPD to COPDAE.

Accumulating evidence has shown a significant correlation between periodontal diseases and systemic diseases. In this study, we investigated the association between the frequency of tooth scaling and acute myocardial infarction (AMI). Here, a group of 7164 participants who underwent tooth scaling was compared with another group of 7164 participants without tooth scaling through propensity score matching to assess AMI risk by Cox’s proportional hazard regression. The results show that the hazard ratio of AMI from the tooth scaling group was 0.543 (0.441, 0.670) and the average expenses of AMI in the follow up period was USD 265.76, while the average expenses of AMI in follow up period for control group was USD 292.47. The tooth scaling group was further divided into two subgroups, namely A and B, to check the influence of tooth scaling frequency on AMI risk. We observed that (1) the incidence rate of AMI in the group without any tooth scaling was 3.5%, which is significantly higher than the incidence of 1.9% in the group with tooth scaling, (2) the tooth scaling group had lower total medical expenditures than those of the other group because of the high medical expenditure associated with AMI, and (3) participants who underwent tooth scaling had a lower AMI risk than those who never underwent tooth scaling had. Therefore, the results of this study demonstrate the importance of preventive medicine.

// 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.

BACKGROUND Few large, prospective, randomized studies have investigated the value and optimal application of neoadjuvant chemoradiotherapy followed by surgery (trimodality therapy) or definitive concurrent chemoradiotherapy (CCRT) for patients with thoracic esophageal squamous cell carcinoma (TESCC). METHODS The authors analyzed data from patients with TESCC in the Taiwan Cancer Registry database. To compare their outcomes, patients with TESCC were enrolled and categorized into the following groups according to treatment modality: group 1, those who underwent surgery alone; group 2, those who received trimodality therapy; and group 3, those who received definitive CCRT. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS In total, 3522 patients who had TESCC without distant metastasis were enrolled. Multivariate Cox regression analysis indicated that a Charlson comorbidity index score ≥3, American Joint Committee on Cancer stage ≥IIA, earlier year of diagnosis, alcohol consumption, cigarette smoking, and definitive CCRT were significant, independent predictors of a poor prognosis. After adjustment for confounders, adjusted hazard ratios and 95% confidence intervals (CIs) for overall mortality in patients with clinical stage I, IIA, IIB, IIIA, IIIB, and IIIC TESCC were 2.01 (95% CI, 0.44-6.18), 1.65 (95% CI, 0.99-2.70), 1.48 (95% CI, 0.91-2.42), 0.66 (95% CI, 1.08-1.14), 0.39 (95% CI, 0.26-0.57), and 0.44 (95% CI, 0.24-0.83), respectively, in group 2; and 2.06 (95% CI, 1.18-3.59), 2.65 (95% CI, 1.76-4.00), 2.25 (95% CI, 1.49-3.39), 1.34 (95% CI, 0.79-2.28), 0.82 (95% CI, 0.57-1.17), and 0.93 (95% CI, 0.51-1.71), respectively, in group 3. CONCLUSIONS Trimodality therapy may be beneficial for the survival of patients with advanced-stage (IIIA-IIIC) TESCC, and CCRT might be an alternative to surgery alone in these patients. Cancer 2017;123:3904-15. © 2017 American Cancer Society.

BACKGROUND Few large, prospective, randomized studies have investigated the effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma (TESCC) who receive definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through modern, intensity modulated-RT (IMRT) techniques. The therapeutic effects of esophagectomy in patients with TESCC were evaluated using modern clinical staging and RT techniques and suitable RT doses. METHODS The authors analyzed data from patients with TESCC from the Taiwan Cancer Registry database. Patients were categorized into the following groups on the basis of treatment modality to compare their outcomes: group 1 received definitive CCRT, group 2 received neoadjuvant RT followed by esophagectomy (total IMRT dose, ≥50 grays [Gy]), and group 3 receiving neoadjuvant CCRT followed by esophagectomy (total IMRT dose, ≥ 50 Gy). The median total RT dose and fraction size were 50.4 Gy and 1.8 Gy per fraction, respectively. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS In total, 3123 patients who had TESCC without distant metastasis were enrolled. Patient ages 65 years and older, Charlson comorbidity index scores ≥3, advanced clinical stages (IIA-IIIC), alcohol consumption, and cigarette smoking were identified as significant, independent poor prognostic risk factors for overall survival in multivariate Cox regression analyses. In group 3, after adjustment for confounders, the adjusted hazard ratios (95% confidence intervals [CIs]) for overall mortality were 0.62 (95% CI, 0.41-0.93) for patients with clinical stage IIA disease, 0.61 (95% CI, 0.41-0.91) for those with clinical stage IIB disease, 0.47 (95% CI, 0.38-0.55) for those with clinical stage IIIA disease, 0.47 (95% CI, 0.39-0.56) for those with clinical stage IIIB disease, and 0.46 (95% CI, 0.37-0.57) for those with clinical stage IIIC disease. CONCLUSIONS Esophagectomy can be beneficial in patients with TESCC after definitive CCRT, especially in those who have advanced-stage disease. Cancer 2017;123:2043–2053. © 2017 American Cancer Society.

Background and Objectives: To investigate critical prognostic factors for local recurrence in patients with rectal adenocarcinoma. Methods: We enrolled 221 consecutive patients who had histologically confirmed adenocarcinoma of the rectum and underwent surgery in our hospital between January 2000 and December 2014. Total mesorectal excision was performed in all patients undergoing a sphincter-sparing procedure or abdominal perineal resection of rectal cancer. To evaluate prognostic factors for local recurrence, we performed univariate and multivariate Cox regression analyses of the local recurrence rate in all patients. Overall survival rates were calculated using the Kaplan-Meier method, and Kaplan-Meier survival curves were compared using the log-rank test. Results: After the inclusion of only model variables of local recurrence with the highest or lowest univariate risk, a tumor size of

We examined the overall survival rates of a national cohort to determine optimal treatments and prognostic factors for patients with metachronous second primary head and neck squamous cell carcinomas (mspHNSCCs) at different stages and sites. We analyzed data of mspHNSCC patients collected from the Taiwan Cancer Registry database. The patients were categorized into four groups based on the treatment modality: Group 1 (control arm; chemotherapy [CT] alone), Group 2 (reirradiation [re‐RT] alone with intensity‐modulated radiotherapy [IMRT]), Group 3 (concurrent chemoradiotherapy alone [irradiation with IMRT]), and Group 4 (salvage surgery with or without RT or CT). We enrolled 1741 mspHNSCC patients without distant metastasis. Multivariate Cox regression analyses revealed that Charlson comorbidity index (CCI) ≥6, stage of second HNSCC, stage of first HNSCC, and duration from first primary HNSCC of