The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma

Yen-Hsiang Huang,Kuo-Hsuan Hsu,Jeng-Sen Tseng,Kun-Chieh Chen,Chia-Hung Hsu,Kang-Yi Su,Jeremy J. W. Chen,Huei-Wen Chen,Sung-Liang Yu,Tsung-Ying Yang,Gee-Chen Chang 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)mutant lung adenocarcinoma patients with acquired resistance after firstline EGFRtyrosine kinase inhibitor (TKI) treatment. Materials and Methods We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFRmutation status. Results A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression- free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). Conclusion PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.

Treatment outcomes of patients with stage II pure endometrioid-type endometrial cancer: a Taiwanese Gynecologic Oncology Group (TGOG-2006) retrospective cohort study

Hung-Chun Fu,Jen-Ruei Chen,Min-Yu Chen,Keng-Fu Hsu,Wen-Fang Cheng,An Jen Chiang,Yu-Min Ke,Yu-Chieh Chen,Yin-Yi Chang,Chia-Yen Huang,Chieh-Yi Kang,Yuan-Yee Kan,Sheng-Mou Hsiao,Ming-Shyen Yen 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.5

Objective: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. Methods: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. Results: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p<0.001), recurrent urinary tract infections (p=0.013), and leg lymphedema (p=0.038). Age over 50-year (HR=9.2; 95% confidence interval [CI], 1.2–70.9) and grade 3 histology (HR=7.28; 95% CI, 1.45–36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR=5.13; 95% CI, 1.38–19.1) and DSS (HR=5.97; 95% CI, 1.06–58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p=0.046), but no impact on survival. Conclusion: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC.

Risk Factors for Recurrent Hypoglycemia in Hospitalized Diabetic Patients Admitted for Severe Hypoglycemia

Yen-Yue Lin,Chin-Wang Hsu,Wayne Huey-Herng Sheu,Shi-Jye Chu,Chin-Pyng Wu,Shih-Hung Tsai 연세대학교의과대학 2010 Yonsei medical journal Vol.51 No.3

Purpose: Severe hypoglycemia can result in neural damage, impaired cognitive function, coma, seizures, or death. The decision to admit diabetic patients after initial treatment in the emergency department remains unclear. Our purpose is to identify risk factors for developing recurrent hypoglycemia in diabetic patients admitted for severe hypoglycemia. Materials and Methods: We reviewed the records of 233 subjects (92 males, 141 females; mean age, 74.1 ± 9.8 years) with type 2 diabetes treated at a tertiary care teaching hospital and hospitalized for severe hypoglycemia. Results: Seventy-four (31.8%) patients were categorized with recurrent hypoglycemia and 159(68.2%) with non-recurrent. Multivariate logistic regression analysis revealed that patients with loss of a recent meal, coronary artery disease, infection, and poor renal function (lower estimated glomerular filtration rate) were at risk for recurrent hypoglycemia. The use of calcium-channel blockers appeared to be a protective factor for the development of recurrent hypoglycemia. Conclusion: There may be a subset of patients with severe hypoglycemia and certain risk factors for recurrent hypoglycemia that should be admitted.

Exploring Tourists`Differences within Perception, Motivation, and Behavior in Cultural Tourism

( Hung-hsu Yen ),( Chun-hao Chang ) 세계문화관광학회 2014 International Journal of Culture and tourism Resea Vol.7 No.1

Cultural tourism is one of the most popular types of tourism nowadays; however, the mass tourism travel behavior can easily be seen in many cultural attractions. The main purposes of this study were to explore: 1) What are the tourists’ motivations while traveling in Anping area. 2) Would the tourists’ behavior in Anping area act with in-depth and learning behavior. 3) Exploring tourists’ perception differences in Anping area. 4) Exploring different tourists’behavior within different cultural involvement groups. This study applied the convenience sampling to collect 295 valid questionnaires. The results showed: 1) Tourists’ motivations in Anping area tended to like mass tourism motivations. 2) Most tourists’ information searching, visiting, and consuming behaviors in Anping area acted like mass tourism travel type. 3) Anping area’s main cultural concept could not be properly delivered to the tourists. 4) Information searching, tourist guide, and cultural related products consuming were less used by high involvement cultural tourists. This study suggested the government should enhance the cultural elements, the historic story, the design of cultural related products and the planning of whole environment. Moreover, the improvement of self-guide system, the training of commentator, and the promotion of the usage of guiding system were still need to be done. Finally, this study suggested the Tourism Bureau should develop a guiding book to encourage and guide the tourists how to enjoy/explore the true culture of each attractions. Moreover, the proper behavior and perception in cultural attractions should also be educated in future education system or promotion activities. To let tourists know the proper perception, behavior, manner and rules in cultural tourism will enhance the future development of cultural tourism in Taiwan.Keywords:Tourism Motivation, Tourism Behavior, Cultural Tourism Perception.

Interpretation and Use of Natriuretic Peptides in Non-Congestive Heart Failure Settings

Shih-Hung Tsai,Yen-Yue Lin,Shi-Jye Chu,Ching-Wang Hsu,Shu-Meng Cheng 연세대학교의과대학 2010 Yonsei medical journal Vol.51 No.2

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases;endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction;monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article.

The Characteristics of Acute Aortic Dissection among Young Chinese Patients: A Comparison between Marfan Syndrome and Non-Marfan Syndrome Patients

Shih-Hung Tsai,Yen-Yue Lin,Chin-Wang Hsu,Yu-Long Chen,Min-Tser Liao,Shi-Jye Chu 연세대학교의과대학 2009 Yonsei medical journal Vol.50 No.2

Purpose: Aortic dissection (AoD) is one of the most common catastrophes involving the aorta. Nevertheless, early diagnosis remains to be a challenge in the Emergency Department (ED), particularly in young individuals. In this study, we attempted to identify the characteristics of acute AoD among young individuals, particular in patients with Marfan syndrome. Materials and Methods: This was an retrospective chart-review study conducted in a tertiary referring hospital. The hospital database was queried for the combination of AoD and patients under age of 40 years. The medical charts were reviewed to obtain demographic data, clinical data and laboratory characteristics by using a standardized data collection sheet. A comparison between Marfan syndrome and non-Marfan syndrome patients was performed. Results: During the 10- years period, 18 of 344 patients with acute AoD were younger than 40 years-old. Patients with Marfan syndrome developed acute AoD at a younger age than patients without Marfan syndrome. The mean diastolic blood pressure was significantly lower in patients with Marfan syndrome upon presenting to the ED than those without. Patients with Marfan syndrome had trends toward higher risk of development of type A AoD, increased recurrence rate and higher mortality rate than those without. However, statistical significance was not present. Conclusion: ED physicians should have high alert to acute AoD in young patients presenting with severe unexplained chest and back pain, particularly in those patients with a history of heart diseases, hypertension, and Marfan syndrome or featuring Marfanoid habitus. Acute coronary syndrome, unexplained abdominal symptoms, and sudden cardiac arrest could be the initial manifestation of AoD in young patients. A low threshold to perform enhanced computed tomography may facilitate early diagnosis and timely treatment in this patient population. Purpose: Aortic dissection (AoD) is one of the most common catastrophes involving the aorta. Nevertheless, early diagnosis remains to be a challenge in the Emergency Department (ED), particularly in young individuals. In this study, we attempted to identify the characteristics of acute AoD among young individuals, particular in patients with Marfan syndrome. Materials and Methods: This was an retrospective chart-review study conducted in a tertiary referring hospital. The hospital database was queried for the combination of AoD and patients under age of 40 years. The medical charts were reviewed to obtain demographic data, clinical data and laboratory characteristics by using a standardized data collection sheet. A comparison between Marfan syndrome and non-Marfan syndrome patients was performed. Results: During the 10- years period, 18 of 344 patients with acute AoD were younger than 40 years-old. Patients with Marfan syndrome developed acute AoD at a younger age than patients without Marfan syndrome. The mean diastolic blood pressure was significantly lower in patients with Marfan syndrome upon presenting to the ED than those without. Patients with Marfan syndrome had trends toward higher risk of development of type A AoD, increased recurrence rate and higher mortality rate than those without. However, statistical significance was not present. Conclusion: ED physicians should have high alert to acute AoD in young patients presenting with severe unexplained chest and back pain, particularly in those patients with a history of heart diseases, hypertension, and Marfan syndrome or featuring Marfanoid habitus. Acute coronary syndrome, unexplained abdominal symptoms, and sudden cardiac arrest could be the initial manifestation of AoD in young patients. A low threshold to perform enhanced computed tomography may facilitate early diagnosis and timely treatment in this patient population.

Hypoglycemia Revisited in the Acute Care Setting

Shih-Hung Tsai,Der-Ming Chu,Yen-Yue Lin,Chin-Wang Hsu,Chien-Sheng Cheng 연세대학교의과대학 2011 Yonsei medical journal Vol.52 No.6

Hypoglycemia is a common finding in both daily clinical practice and acute care settings. The causes of severe hypoglycemia (SH) are multi-factorial and the major etiologies are iatrogenic, infectious diseases with sepsis and tumor or autoimmune diseases. With the advent of aggressive lowering of HbA1c values to achieve optimal glycemic control, patients are at increased risk of hypoglycemic episodes. Iatrogenic hypoglycemia can cause recurrent morbidity, sometime irreversible neurologic complications and even death, and further preclude maintenance of euglycemia over a lifetime of diabetes. Recent studies have shown that hypoglycemia is associated with adverse outcomes in many acute illnesses. In addition, hypoglycemia is associated with increased mortality among elderly and non-diabetic hospitalized patients. Clinicians should have high clinical suspicion of subtle symptoms of hypoglycemia and provide prompt treatment. Clinicians should know that hypoglycemia is associated with considerable adverse outcomes in many acute critical illnesses. In order to reduce hypoglycemia-associated morbidity and mortality, timely health education programs and close monitoring should be applied to those diabetic patients presenting to the Emergency Department with SH. ED disposition strategies should be further validated and justified to achieve balance between the benefits of euglycemia and the risks of SH. We discuss relevant issues regarding hypoglycemia in emergency and critical care settings.

Assistive Control of a Surgical Robot Based on Bilateral Interacted Force Analysis

Ping-Lang Yen,Shang-Wei Hsu,Hang-Ting Lin,Ching-Heng Wang 제어로봇시스템학회 2012 제어로봇시스템학회 국제학술대회 논문집 Vol.2012 No.10

Interacted force between a robot, human and anatomical object in orthopedic surgery provides crucial information for safe and accurate bone cutting. When the robot plays the role of assisting the surgeon in the whole surgical procedure, the robot is trying to comply with the human intention according to various cutting conditions. The reaction force to the robot from the human is for indicating human intention, whereas the force from the anatomical object reflects the cutting condition. In this paper two impedance indices are defined by these two interacted forces and a surgical robot then decides whether assistive or resistant action is activated so that accuracy and safety of bone cutting can be achieved.

Successful Enrichment of Rarely Found Candidatus Anammoxoglobus propionicus from Leachate Sludge

( Shu Chuan Hsu ),( Yen Chun Lai ),( Ping Heng Hsieh ),( Pun Jen Cheng ),( Suen Shin Wong ),( Chun Hsiung Hung ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.7

Bacteria that mediate the anaerobic oxidation of ammonium (anammox) have been detected in natural ecosystems, as well as various wastewater treatment systems. In this study, sludge from a particular landfill leachate anaerobic treatment system was selected as the incubation seed for anammox microorganism enrichment owing to its possible anammox activity. Transmission electron microscopy observation, denaturing gradient gel electrophoresis analysis, and cloning/sequencing techniques were applied to identify the diversity of anammox microorganisms throughout the incubation. During the early stage of operation, the diversity of anammox microorganisms was similar to the original complex microbes in the seed sludge. However, as incubation time increased, the anammox microorganism diversity within the system that was originally dominated by Candidatus (Ca.) Brocadia sp. was replaced by Ca. Anammoxoglobus propionicus. The domination of Ca. Anammoxoglobus propionicus produced a stable removal of ammonia (70 mg-N/l) and nitrite (90 mg-N/l), and the total nitrogen removal efficiency was maintained at nearly 95%. The fluorescence in situ hybridization results showed that Ca. Anammoxoglobus propionicus was successfully enriched from 1.8 ± 0.6% initially to 65 ± 5% after 481 days of operation. Therefore, the present results demonstrated the feasibility of enriching Ca. Anammoxoglobus propionicus from leachate sludge, even though the original cell count was extremely low. Application of this seldom found anammox organism could offer an alternative to current ammonia-nitrogen treatment.

Research on Using Six Sigma Tool to Reduce the Core Process Time

Chung, Yi-Chan,Yen, Tieh-Min,Hsu, Yau-Wen,Tsai, Chih-Hung,Chen, Ching-Piao The Korean Society for Quality Management 2008 The Asian Journal on Quality Vol.9 No.1

When facing the global severe competition, the enterprises all try their best to upgrade the quality, reduce the costs to reach the goal of customer satisfaction. Motorola was the earliest firm creating the term Six Sigma (6 ${\sigma}$); GE was the enterprise successfully fulfilling Six Sigma. The success of these two firms revealed the prominent effects and became the world-class model enterprises. The main purpose of promoting Six Sigma activity was to reduce the possible defects in the business process to the least through designing and monitoring business process in order to reach the goals such as the best quality and efficiency, the lowest costs, the shortest circular process time, maximum profits and customer satisfaction. This research used the Six Sigma technique to improve the business process of ceramics manufacturing plant and find out the major factors of slower core task time by the analytical process of Process Mapping, Pareto Chart, Simu18 simulation software and figures and proposed the improvement measures. Through the confirmation of the case companies, it successfully reduced the core process time and the organizational costs and increased the capacity.