Publications by authors named "Chia-Che Wu"

39 Publications

Machine-Based Hand Massage Ameliorates Preoperative Anxiety in Patients Awaiting Ambulatory Surgery.

J Nurs Res 2021 Apr 12;29(3):e152. Epub 2021 Apr 12.

MS, RN, Executive Director of Community Medicine, Center for Nursing and Healthcare Research in Clinical Practice Application, Wan Fang Hospital, Taipei Medical University, and Adjunct Assistant Professor, School of Nursing, College of Nursing, Taipei Medical University, Taiwan, ROC.

Background: Hand massage therapies have been used to relieve anxiety and pain in various clinical situations. The effects of machine-based hand massage on preoperative anxiety in ambulatory surgery settings have not been evaluated.

Purpose: This prospective study was designed to investigate the effect of machine-based hand massage on preoperative anxiety and vital signs in ambulatory surgery patients.

Methods: One hundred ninety-nine patients aged 18 years and older who were scheduled to receive ambulatory surgery were recruited from the Taipei Municipal Wanfang Hospital in Taipei City, Taiwan. The patients were assigned randomly to the experimental group (n = 101), which received presurgical machine-based hand massage therapy, and the control group (n = 98), which received no intervention. The patients in both groups completed the Spielberger State-Trait Anxiety Inventory short form at preintervention (baseline) and postintervention.

Results: Within-group comparisons of Spielberger State-Trait Anxiety Inventory short form scores showed significant decreases between preintervention and postintervention scores in the experimental group (44.3 ± 11.2 to 37.9 ± 8.7) and no significant change in the control group. Within-group comparisons of vital signs revealed a significant increase in mean respiration rate between baseline and postintervention in both groups (both ps < .05). Blood pressure was found to have decreased significantly only in the control group at postintervention (p < .05). No significant preintervention to postintervention change in pulse was observed in either group.

Conclusions: The findings of this study indicate that machine-based hand massage reduces anxiety significantly in patients awaiting ambulatory surgery while not significantly affecting their vital signs.
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http://dx.doi.org/10.1097/jnr.0000000000000432DOI Listing
April 2021

A Piezoelectric Wave-Energy Converter Equipped with a Geared-Linkage-Based Frequency Up-Conversion Mechanism.

Sensors (Basel) 2020 Dec 30;21(1). Epub 2020 Dec 30.

Department of Mechanical Engineering, National Chung Hsing University, Taichung 40227, Taiwan.

In this paper, a piezoelectric wave-energy converter (PWEC), consisting of a buoy, a frequency up-conversion mechanism, and a piezoelectric power-generator component, is developed. The frequency up-conversion mechanism consists of a gear train and geared-linkage mechanism, which converted lower frequencies of wave motion into higher frequencies of mechanical motion. The slider had a six-period displacement compared to the wave motion and was used to excite the piezoelectric power-generation component. Therefore, the operating frequency of the piezoelectric power-generation component was six times the frequency of the wave motion. The developed, flexible piezoelectric composite films of the generator component were used to generate electrical voltage. The piezoelectric film was composed of a copper/nickel foil as the substrate, lead-zirconium-titanium (PZT) material as the piezoelectric layer, and silver material as an upper-electrode layer. The sol-gel process was used to fabricate the PZT layer. The developed PWEC was tested in the wave flume at the Tainan Hydraulics Laboratory, Taiwan (THL). The maximum height and the minimum period were set to 100 mm and 1 s, respectively. The maximum voltage of the measured value was 2.8 V. The root-mean-square (RMS) voltage was 824 mV, which was measured through connection to an external 495 kΩ resistive load. The average electric power was 1.37 μW.
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http://dx.doi.org/10.3390/s21010204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795976PMC
December 2020

Safety and Efficacy of Immune Checkpoint Inhibitors for Patients With Metastatic Urothelial Carcinoma and End-Stage Renal Disease: Experiences From Real-World Practice.

Front Oncol 2020 27;10:584834. Epub 2020 Nov 27.

Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.

Background: Immune checkpoint inhibitors (ICIs) are used widely for treating metastatic urothelial carcinoma (mUC). In practical settings, evidence is lacking on the efficacy of ICIs in some difficult-to-treat patients, such as those with end-stage renal disease (ESRD). Herein, we evaluate the safety and efficacy of ICIs for patients with mUC and ESRD.

Methods: For this retrospective study, patients with mUC who were given ICIs at Kaohsiung Chang Gang Memorial Hospital and Linkou Chang Gung Memorial Hospital between April 2016 and November 2019 were consecutively enrolled. All clinicopathologic data, treatment responses, and adverse events were recorded. The immune-related adverse events (AEs), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between ESRD and non-ESRD groups.

Results: In total, 129 patients with mUC were enrolled, with 11 patients categorized as the ESRD group. Among these patients with ESRD receiving ICIs, 7 of 11 (63.6%) had high-grade (grade ≥3) AEs, chiefly hematologic toxicity. Some rarely encountered AEs were noted, including toxic epidermal necrolysis, tuberculosis reactivation, ascites, and cytokine release syndrome. Patients in the ESRD group had numerically higher ORR (54.5% vs. 28.8%, p = 0.09), PFS (7.1 vs. 3.5 months, p = 0.42), and OS (not reached vs. 15.4 months) than the non-ESRD group. A multivariate Cox regression model demonstrated that leukocytosis (hazard ratio [HR]: 2.63; 95% confidence interval [CI]: 1.23-5.63; p = 0.01) and neutrophil-to-lymphocyte ratio (HR 2.91; 95% CI: 1.30-6.53; p = 0.01) were independent prognostic factors.

Conclusion: Administration of ICIs in patients with mUC and ESRD demonstrated a modest antitumor activity, and should be used with caution for increasing risk of hematologic toxicity.
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http://dx.doi.org/10.3389/fonc.2020.584834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729012PMC
November 2020

Effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries: a systemic review and meta-analysis.

Braz J Otorhinolaryngol 2020 May - Jun;86(3):376-382. Epub 2020 Feb 12.

Taipei Medical University, Wang Fang Hospital, Department of Otorhinolaryngology, Taipei, Taiwan; Taipei Medical University, School of Medicine, Department of Otorhinolaryngology, Taipei, Taiwan. Electronic address:

Introduction: Packing of the nasal cavity has traditionally been used for postoperative bleeding control and decreasing synechia formation in patients undergoing nasal surgeries. Although absorbable nasal packing has been gaining popularity in the recent years, nonabsorbable nasal packing is still often used in nasal surgeries in various parts of the world. It is known to be associated with pain and discomfort especially upon and during removal, and previous reviews have only evaluated the effects of local anesthetic infiltration of nasal packing in septal surgeries.

Objective: To evaluate the effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries MATERIALS AND METHODS: We searched the PubMed and Embase databases from their earliest record to April 27, 2019, randomized controlled trials and prospective controlled trials for review, and included only randomized controlled trials for data analysis. We included studies using topical anesthetics-infiltrated nasal packing following sinonasal surgeries and evaluated the effectiveness compared to placebo packing in pain reduction during postoperative follow up, as well as the effectiveness in anxiety reduction.

Results: Among 15 studies included for review, 9 studies involving 765 participants contributed to the meta-analysis. In terms of pain reduction, our analysis showed significant standard mean differences regarding effectiveness at postoperative 1, 12, 24 h interval for all surgical groups combined, in the sinus surgery group, as well as during nasal packing removal. There was no consistent evidence to support the effectiveness in anxiety reduction.

Conclusions: Our study supports anesthetics infiltration of nasal packing as an effective method in managing pain in patients with nasal packing after sinonasal surgeries. However, the level of evidence is low. More high-quality randomized controlled trials are needed to establish its effectiveness in reducing anxiety. We believe this review is of great clinical significance due to the vast patient population undergoing sinonasal surgeries. Postoperative local hemorrhage remains the greatest concern for ear nose and throat surgeons due to the rich vasculature of the nose and sinuses. Sinonasal packing provides structural support and serves as an important measure for hemostasis and synechia formation. Although absorbable packing has been gaining popularity in the recent years, nonabsorable packing materials are still used in many countries due to lower cost. Infiltration of nasal packing with local anesthetic provides a solution to the discomfort, nasal pressure and nasal pain experienced commonly by the patients as evidenced by our analysis.
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http://dx.doi.org/10.1016/j.bjorl.2019.12.011DOI Listing
June 2020

Comparative Study of the Safety and Efficacy of First-Line Cisplatin and Carboplatin Chemotherapy in Elderly Patients with Metastatic Urothelial Carcinoma.

Oncology 2020 3;98(3):146-153. Epub 2019 Dec 3.

Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, Taiwan,

Objectives: Platinum-based chemotherapy is the standard treatment for metastatic urothelial carcinoma (mUC). However, considering elderly patients often experience comorbidities and frailty, the utility of cisplatin-based chemotherapy for elderly patients is still debatable. We conducted this study to compare the safety and efficacy of carboplatin and cisplatin in elderly patients with mUC.

Methods: This retrospective study enrolled elderly patients with mUC (defined as aged ≥70 years) who underwent first-line platinum-based chemotherapy between September 2001 and October 2018. The primary endpoints were chemotherapy-related adverse events (AEs), including treatment-related hospitalization or death. The secondary outcomes were overall survival (OS) and progression-free survival calculated by Kaplan-Meier analysis.

Results: In total, 108 elderly patients with mUC were enrolled and allocated into the cisplatin or carboplatin group. Patients treated with carboplatin-based chemotherapy had a significantly higher incidence of all grade ≥3 AEs (78.8 vs. 50.0%, p = 0.008) than those on cisplatin. AE-related hospitalization (47.5 vs. 19.1%, p = 0.002) and treatment-related death (17.5 vs. 4.4%, p = 0.02) were significantly increased in the carboplatin group. In the univariate analysis, the median OS in the cisplatin group was significantly increased compared with the carboplatin group (13.6 vs. 7.2 months, p = 0.045). The Cox multivariate regression model indicated that leukocytosis (HR 3.17, 95% CI 1.84-5.46, p < 0.001) and anemia (HR 2.02, 95% CI 1.11-3.65, p = 0.02) were independent prognostic factors.

Conclusion: Elderly patients with mUC treated with cisplatin-based chemotherapy had better survival and safety profiles than those treated with carboplatin. Age itself was not a crucial factor in determining cisplatin eligibility.
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http://dx.doi.org/10.1159/000504393DOI Listing
March 2020

Presence of Chronic Obstructive Pulmonary Disease (COPD) Impair Survival in Lung Cancer Patients Receiving Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI): A Nationwide, Population-Based Cohort Study.

J Clin Med 2019 Jul 12;8(7). Epub 2019 Jul 12.

Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 83301, Taiwan.

The emergence of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) caused a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). Although several clinicopathologic factors to predict the response to and survival on EGFR-TKI were recognized, its efficacy has not been confirmed for patients with underlying pulmonary disease, such as chronic obstructive pulmonary disease (COPD). We conducted the study to evaluate the impact of COPD on survival for NSCLC patients that underwent EGFR-TKI treatment. The nationwide study obtained clinicopathologic data from the National Health Insurance Research Database in Taiwan between 1995 and 2013. Patients receiving EGRR-TKI were divided into COPD and non-COPD groups, and adjusted for age, sex, comorbidities, premium level and cancer treatments. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier analysis. In total, 21,026 NSCLC patients were enrolled, of which 47.6% had COPD. After propensity score (PS) matching, all covariates were adjusted and balanced except for age ( < 0.001). In the survival analysis, the median OS (2.04 vs. 2.28 years, < 0.001) and PFS (0.62 vs. 0.69 years, < 0.001) of lung cancer with COPD were significantly worse than those without COPD. Lung cancer patients on EGFR-TKI treatment had a worse survival outcome if patients had pre-existing COPD.
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http://dx.doi.org/10.3390/jcm8071024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678274PMC
July 2019

Co-Delivery of Natural Compounds with a Dual-Targeted Nanoparticle Delivery System for Improving Synergistic Therapy in an Orthotopic Tumor Model.

ACS Appl Mater Interfaces 2019 Jul 25;11(27):23880-23892. Epub 2019 Jun 25.

Various natural compounds including epigallocatechin gallate (EGCG) and curcumin (CU) have potential in developing anticancer therapy. However, their clinical use is commonly limited by instability and low tissue distribution. EGCG and CU combined treatment can improve the efficacy with synergistic effects. To improve the synergistic effect and overcome the limitations of low tissue distribution, we applied a dual cancer-targeted nanoparticle system to co-deliver EGCG and CU. Nanoparticles were composed of hyaluronic acid, fucoidan, and poly(ethylene glycol)-gelatin to encapsulate EGCG and CU. Furthermore, a dual targeting system was established with hyaluronic acid and fucoidan, which were used as agents for targeting CD44 on prostate cancer cells and P-selectin in tumor vasculature, respectively. Their effect and efficacy were investigated in prostate cancer cells and a orthotopic prostate tumor model. The EGCG/CU-loaded nanoparticles bound to prostate cancer cells, which were uptaken more into cells, leading to a better anticancer efficiency compared to the EGCG/CU combination solution. In addition, the releases of EGCG and CU were regulated by their pH value that avoided the premature release. In mice, treatment of the cancer-targeted EGCG/CU-loaded nanoparticles significantly attenuated the orthotopic tumor growth without inducing organ injuries. Overall, the dual-targeted nanoparticle system for the co-delivery of EGCG and CU greatly improved its synergistic effect in cancer therapy, indicating its great potential in developing treatments for prostate cancer therapy.
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http://dx.doi.org/10.1021/acsami.9b06155DOI Listing
July 2019

Inflammation-based prognostic scores predict the prognosis of locally advanced cervical esophageal squamous cell carcinoma patients receiving curative concurrent chemoradiotherapy: a propensity score-matched analysis.

PeerJ 2018 19;6:e5655. Epub 2018 Sep 19.

Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Introduction: The present study investigated the crucial role of inflammation-based prognostic scores in locally advanced cervical esophageal squamous cell carcinoma (ESCC) patients who underwent curative concurrent chemoradiotherapy (CCRT).

Methods: There were 411 ESCC patients enrolled, including 63 cervical ESCC patients. Using the propensity score matching method, 63 thoracic ESCC patients were matched to the 63 cervical ESCC patients. The inflammation-based prognostic scores included the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), albumin level, c-reactive protein (CRP) level, modified Glasgow prognostic score (mGPS), and CRP/albumin ratio. The chi-square test and Kaplan-Meier method were used for categorical variable data and overall survival, respectively. A Cox regression model was performed for univariate and multivariable analyses.

Results: With respect to cervical ESCC, NLR ≥ 2.5 ( = 0.019), PLR ≥ 103 ( = 0.013), CRP value >10 mg/l ( = 0.040), mGPS ≥ 1 ( = 0.040), and CRP/albumin ratio ≥ 9.5 ( = 0.033) were significant predictors of worse overall survival (OS) in the univariate analysis. In a multivariable analysis, PLR ≥ 103 ( = 0.010, HR: 2.66, 95% CI [1.27-5.58]) and mGPS ≥ 1 ( = 0.030, HR: 2.03, 95% CI [1.07-3.86]) were the independent prognostic parameters of worse OS. The prognostic value of these biomarkers in the matched thoracic ESCC patients was similar and compatible with the results in the cervical ESCC group in the univariate and multivariable analyses.

Conclusions: Our study suggests that these inflammation-based prognostic scores are helpful in clinical practice, and PLR and mGPS may predict the prognosis for locally advanced cervical ESCC patients who receive curative CCRT.
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http://dx.doi.org/10.7717/peerj.5655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151110PMC
September 2018

Cost-effectiveness analysis of endoscopic tympanoplasty versus microscopic tympanoplasty for chronic otitis media in Taiwan.

J Chin Med Assoc 2018 03 26;81(3):284-290. Epub 2017 Dec 26.

Department of Otolaryngology, Wan Fang Medical Center, Taipei Medical University, Taipei, Taiwan, ROC.

Background: Health care systems and physicians need to conform to budgets and streamline resources to provide cost-effective quality care. Although endoscopic tympanoplasty (ET) has been performed for decades, no studies on the cost-effectiveness of ET and microscopic tympanoplasty (MT) for treating chronic otitis media have been published. The present study aimed to compare the cost-effectiveness of ET and MT for treating chronic otitis media.

Methods: This study was performed using a Cohort-style Markov decision-tree economic model with a 30-year time horizon. The economic perspective was that of a third-party payer (Taiwan National Health Insurance System). Two treatment strategies were compared, namely ET and MT. The primary outcome was the incremental cost per quality-adjusted life year (QALY). Probabilities were obtained from meta-analyses. Costs were obtained from the published literature and Taiwan National Health Insurance System database. Multiple sensitivity analyses were performed to account for data uncertainty.

Results: The reference case revealed that the total cost of ET was $NT 20,901 for 17.08 QALY per patient. By contrast, the total cost of MT was $NT 21,171 for 17.15 QALY per patient. The incremental cost effectiveness ratio for ET versus that of MT was $NT 3703 per QALY. The cost-effectiveness acceptability curve indicated that ET was comparable to MT at a willingness-to-pay threshold of larger than $NT 35,000 per QALY.

Conclusion: This cost-effectiveness analysis indicates that ET is comparable to MT for treating chronic otitis media in Taiwan. This result provides the latest information for physicians, the government, and third-party payers to select proper clinical practice.
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http://dx.doi.org/10.1016/j.jcma.2017.06.024DOI Listing
March 2018

Short-term Subjective and Objective Outcomes of Patients Receiving Endoscopic Transcanal Myringoplasty for Repairing Tympanic Perforations.

Otolaryngol Head Neck Surg 2018 02 17;158(2):337-342. Epub 2017 Oct 17.

1 Department of Otolaryngology, Wan Fang Medical Center, Taipei Medical University, Taipei, Taiwan.

Objective Endoscopic transcanal myringoplasty (ETM) has been an emerging technique for repairing tympanic perforations since the late 1990s. Objective outcomes (ie, graft success rates and hearing results) of patients who received ETM are well documented; however, subjective outcomes of these patients have rarely been reported. Hence, this study evaluated subjective and objective outcomes of patients who received ETM for repairing tympanic perforations. Study Design Prospective study. Setting Tertiary care university hospital. Patients and Methods Patients who underwent ETM for perforations of the tympanic membrane were included. We evaluated subjective variables of patients receiving ETM as the primary outcome and objective variables as the secondary outcome. Results In total, 91 ears that underwent ETM were included. The mean pain scale score was 0.1 (range, 0-2) on postoperative day 3. The mean duration of pain medication was 2.0 (range, 0-3) days. The mean number of days required to resume routine activities was 1.0 (range, 1-2) days. The overall graft success was determined postoperatively at 3 months in 80 of 91 ears (87.9%). Closure of the air-bone gap to within 20 dB was achieved in 79 (86.8%) ears. Conclusion In this study, patients who received ETM had mild postoperative pain and resumed routine activities early. These patients also exhibited favorable graft success rates and hearing results at 3 months postoperatively. On the basis of our results, we conclude that patients who receive ETM for the repair of tympanic perforations have favorable short-term subjective and objective outcomes.
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http://dx.doi.org/10.1177/0194599817735501DOI Listing
February 2018

Locoregionally recurrent head and neck squamous cell carcinoma: incidence, survival, prognostic factors, and treatment outcomes.

Oncotarget 2017 Aug 17;8(33):55600-55612. Epub 2017 Mar 17.

Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Purpose: For locoregionally recurrent head and neck squamous cell carcinoma (HNSCC), appropriate therapeutic decisions remain unclear. We examined the treatment outcomes of a national cohort to determine suitable treatments for and prognostic factors in patients with locoregionally recurrent HNSCCs at different stages and sites.

Patients And Methods: We analyzed data of >20-year-old patients with HNSCC at American Joint Committee on Cancer clinical stages I-IV without metastasis from Taiwan National Health Insurance and cancer registry databases. The index date was the date of recurrent HNSCC diagnosis. Recurrent HNSCC was defined as the annotation of locoregional recurrence with tissue proof in cancer registry databases. The enrolled patients were categorized into three groups: Group 1 comprised those undergoing chemotherapy (CT) alone; Group 2 comprised those receiving reirradiation (re-RT) alone (total radiation dose ≥ 60 Gy through intensity modulation radiation therapy [IMRT]); Group 3 comprised those receiving concurrent chemoradiotherapy (CCRT) alone (irradiation total dose ≥60 Gy through IMRT); and Group 4 comprised those receiving salvage surgery with or without RT or CT.

Results: We enrolled 4,839 and 28,664 HNSCC patients with and without locoregional recurrence, respectively (median follow-up, 3.25 years). Locoregional recurrence rate and incidence were 14.44% and 40.73 per 1,000 person-years, respectively. Age ≥ 65 years, Charlson comorbidity index (CCI) score > 6, advanced clinical stage at first diagnosis, and recurrence-free interval < 1 year were significant independent prognostic risk factors for overall survival as per univariate and multivariate Cox regression analyses. After adjusting for age, sex, CCI scores, clinical stage at first diagnosis, and recurrence-free interval, adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for overall mortality in recurrent clinical stages I and II were 0.63 (0.45-0.89, = 0.009), 0.65 (0.52-0.83, < 0.001), and 0.32 (0.26-0.40, < 0.001) in Groups 2, 3, and 4, respectively, whereas they were 1.23 (0.99-1.52, = 0.062), 0.69 (0.60-0.79, < 0.001), and 0.39 (0.34-0.44, < 0.001) for Groups 2, 3, and 4, respectively, for overall mortality in recurrent clinical stage III and IV.

Conclusions: Age, CCI score, clinical stage at first diagnosis, and recurrence-free interval are significant independent prognostic factors for overall survival of recurrent HNSCC patients. Regardless of recurrence stage or site, salvage surgery is the recommended first recurrent HNSCC treatment choice. Re-RT alone and CCRT are more suitable for inoperable recurrent early-stage oral and nonoral cavity recurrent HNSCCs, respectively.
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http://dx.doi.org/10.18632/oncotarget.16340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589686PMC
August 2017

Endoscopic transcanal myringoplasty for tympanic perforations: An outpatient minimally invasive procedure.

Auris Nasus Larynx 2018 Jun 21;45(3):433-439. Epub 2017 Jul 21.

Department of Otolaryngology, Wan Fang Medical Center, Taipei Medical University, Taiwan.

Objective: Since the 1950s, microscopic myringoplasty has been the standard surgery for repairing a perforated tympanic membrane. In addition to conventional microscopic myringoplasty, endoscopic myringoplasty has been an emerging technique since the late 1990s. This study evaluated the efficacy of endoscopic transcanal myringoplasty for repairing tympanic perforations and examined the minimally invasive feature of this technique (no postauricular incision, no canalplasty).

Methods: We retrospectively reviewed the medical records of patients who underwent endoscopic transcanal myringoplasty for perforations of the tympanic membrane. The main outcome was the overall rate of graft success of endoscopic transcanal myringoplasty.

Results: A total of 181 patients were included in the analysis. The overall graft success was determined in 163 of 181 patients (92.8%). The mean preoperative and postoperative air-bone gaps were 19.3dB and 7.8dB, respectively, revealing a significant improvement of 11.5dB (Cohen's d, 1.27; 95% CI, 1.03-1.50; P<0.05; paired t test) in the air-bone gap. The rate of graft success with partial visualization of the perforation margin was comparable to that with complete visualization of the perforation margin. Larger sizes of perforations were significantly associated with lower rates of graft success (P<0.01).

Conclusion: Our study revealed that the rate of graft success and hearing results of endoscopic transcanal myringoplasty and microscopic myringoplasty are comparable for repairing perforations of the tympanic membrane. Visualization of the perforation margin by otoscopy did not affect the rate of graft success. However, endoscopic transcanal myringoplasty is less invasive because this technique does not require postauricular incision, canalplasty, and general anesthesia.
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http://dx.doi.org/10.1016/j.anl.2017.07.003DOI Listing
June 2018

Learning curve for endoscopic tympanoplasty: Initial experience of 221 procedures.

J Chin Med Assoc 2017 Aug 29;80(8):508-514. Epub 2017 Apr 29.

Department of Otolaryngology, Wan Fang Medical Center, Taipei Medical University, Taipei, Taiwan, ROC.

Background: The learning curve for endoscopic tympanoplasty has never been quantitatively reported. The present study depicted the learning curve for endoscopic tympanoplasty and evaluated how many procedures an otologist requires to attain proficiency in this technique.

Methods: We reviewed the medical charts of consecutive patients who underwent endoscopic tympanoplasty between January 1, 2013 and June 1, 2015. We enrolled patients with simple perforations of the tympanic membrane and excluded those with ossicular chain disease. The main outcome was learning curves for endoscopic tympanoplasty, which illustrated changes in the mean operative time and graft success rate according to the patient numbers. We subsequently estimated and verified the threshold value using statistical methods.

Results: A total of 221 procedures were included. For the learning curve of the mean operative time, the time gradually decreased from 75 minutes to 55 minutes. After the 150 patient, the mean operative time stabilized to < 60 minutes. For the learning curve of the graft success rate, the rate sharply increased from 75% to 95%. After the 50 patient, the graft success rate reached a plateau and fluctuated between 85% and 100%. We subsequently verified that the 50 and 150 patients were appropriate threshold values. Moreover, the graft success rate of perforations < 50% was significantly higher than that of perforations > 50%.

Conclusion: These curves illustrate significant progress of the surgeon during the first 50 patients, considering the graft success rate, reaching an advanced level after the 150 patient, considering the mean operating time.
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http://dx.doi.org/10.1016/j.jcma.2017.01.005DOI Listing
August 2017

Comparison of endoscopic transcanal myringoplasty and endoscopic type I tympanoplasty in repairing medium-sized tympanic perforations.

Auris Nasus Larynx 2017 Dec 22;44(6):672-677. Epub 2017 Jan 22.

Department of Otolaryngology, Wan Fang Medical Center, Taipei Medical University, Taiwan.

Objective: The tympanomeatal flap elevation technique has been used in tympanoplasty for decades; however, this procedure has disadvantages. In recent years, endoscopic transcanal myringoplasty (ETM) has been increasingly practiced and has yielded positive results.This study compares the efficacy of ETM and endoscopic type I tympanoplasty (ETT) in repairing medium-sized perforations of the tympanic membrane.

Methods: This retrospective medical record review included patients undergoing surgery for medium-sized perforations of the tympanic membrane from January 1, 2013 to August 1, 2015. We divided our patients into 2 groups: the ETM group and ETT group. The main outcome measure was comparison of the graft take rates and hearing results between ETM and ETT.

Results: A total of 113 patients were enrolled in this study; of these patients, 64 underwent ETM and 49 received ETT. The overall graft take rates and improvement of air-bone gaps were comparable between the groups. However, the patients in the ETM group had shorter operative times and fewer follow-up visits over 3 months than those in the ETT group did.

Conclusion: We recommend that ETM (instead of ETT) be used for repairing medium-sized perforations of the tympanic membrane.
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http://dx.doi.org/10.1016/j.anl.2016.12.007DOI Listing
December 2017

Determining the cleavage site for the mature antimicrobial peptide of Nile tilapia β-defensin using 2D electrophoresis, western blot, and mass spectrometry analysis.

Fish Shellfish Immunol 2017 Mar 9;62:41-46. Epub 2017 Jan 9.

Department of Marine Biotechnology, National Kaohsiung Marine University, 142 Hai-Chuan Road, Kaohsiung 81157, Taiwan.

Several proteomic techniques were used to determine the cleavage site of the mature antimicrobial peptide of Nile tilapia β-defensin. The computer-predicted Nile tilapia β-defensin (ASFPWSCLSLSGVCRKVCLPTELFFGPLGCGKGSLCCVSHFL) composed of 42 amino acids was chemically synthesized and prepared to produce an antibody for Western blotting. Total proteins from the skin of the Nile tilapia were separated on two-dimensional electrophoresis, and the spot of Nile tilapia β-defensin was recognized using Western blot analysis. It was then excised and extracted from the gel. The precise molecular mass of this spot was determined by LC-MS/MS spectrometry. Four major peptides were discovered, with molecular weights of 4293.2 Da, 4306.5 Da, 4678.9 Da, and 4715.0 Da. The calculated mass of the 40-amino-acid sequence (FPWSCLSLSGVCRKVCLPTELFFGPLGCGKGSLCCVSHFL) of Nile tilapia β-defensin starting from Phe27 and ending with Leu66 was 4293.18 Da, which completely matched the 4293.2 Da peptide that was obtained from the mass spectrometry analysis. This result confirmed that the cleavage site for the mature C-terminal Nile tilapia β-defensin is at residue Ser26-Phe27, not at Ala24-25 as predicted by computer analysis. This study provides a simple but reliable model to determine the cleavage site for a mature antimicrobial peptide.
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http://dx.doi.org/10.1016/j.fsi.2017.01.010DOI Listing
March 2017

Survival prognostic factors for metachronous second primary head and neck squamous cell carcinoma.

Cancer Med 2017 01 17;6(1):142-153. Epub 2016 Dec 17.

Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.

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 <3 years were significant poor independent prognostic risk factors for overall survival. After adjustment, adjusted hazard ratios and 95% confidence intervals for the overall all-cause mortality risk at mspHNSCC clinical stages III and IV were 0.72 (0.40-1.82), 0.52 (0.35-0.75), and 0.32 (0.22-0.45) in Groups 2, 3, and 4, respectively. A Cox regression analysis indicated that a re-RT dose of ≥6000 cGy was an independent protective prognostic factor for treatment modalities. CCI ≥ 6, stage of second HNSCC, stage of first HNSCC, and duration from first primary HNSCC of <3 years were significant poor independent prognostic risk factors for overall survival. A re-RT dose of ≥6000 cGy may be necessary for mspHNSCCs.
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http://dx.doi.org/10.1002/cam4.976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269705PMC
January 2017

Comparison of the efficacy of endoscopic tympanoplasty and microscopic tympanoplasty: A systematic review and meta-analysis.

Laryngoscope 2017 08 9;127(8):1890-1896. Epub 2016 Nov 9.

Department of Otolaryngology, Wan Fang Medical Center, Taipei Medical University, Taipei, Taiwan.

Objectives: Microscopic tympanoplasty has been the standard surgery for repairing perforated tympanic membranes since the 1950s, but endoscopic tympanoplasty has been increasingly practiced since the late 1990s. In this study, we compared the efficacies of endoscopic and microscopic tympanoplasty.

Data Sources: PubMed, Embase, MEDLINE, and the Clinical Trial Register.

Review Methods: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. We included clinical studies that compared the efficacies of endoscopic and microscopic tympanoplasty. We assessed the risk of bias and calculated the pooled relative risk (RR) estimates with 95% confidence interval (CI).

Results: We identified four studies (involving 266 patients in total) that met the inclusion criteria. The pooled tympanic membrane closure rates and hearing results of endoscopic and microscopic tympanoplasty were comparable (85.1% vs. 86.4%, respectively; RR: 0.98; 95% CI: 0.85 to 1.11; I = 0) (mean difference of improvements of air-bone gaps: -2.73; 95% CI: -6.73 to 1.28; I = 80%). The pooled canalplasty rate of endoscopic tympanoplasty was significantly lower than that of microscopic tympanoplasty. Patients receiving endoscopic tympanoplasty had a more desirable cosmetic result than did those receiving microscopic tympanoplasty.

Conclusions: Our up-to-date review evidences the comparable tympanic membrane closure rates and hearing results for endoscopic and microscopic tympanoplasty. Patients receiving endoscopic tympanoplasty have a lower canalplasty rate and more desirable cosmetic result than do those receiving microscopic tympanoplasty. Laryngoscope, 127:1890-1896, 2017.
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http://dx.doi.org/10.1002/lary.26379DOI Listing
August 2017

Endoscopic Transcanal Myringoplasty for Anterior Perforations of the Tympanic Membrane.

JAMA Otolaryngol Head Neck Surg 2016 11;142(11):1088-1093

Department of Otolaryngology, Wan Fang Medical Center, Taipei Medical University, Taipei, Taiwan.

Importance: Repairing anterior perforations of the tympanic membrane has been challenging for otolaryngologists. Therefore, devising a simple and effective technique for performing the repair is crucial.

Objective: To assess the results of endoscopic transcanal myringoplasty for repairing anterior perforations of the tympanic membrane.

Design, Setting, And Participants: This medical record review included 59 patients who underwent endoscopic transcanal myringoplasty from January 1, 2013, to June 1, 2015, at PoJen General Hospital, Taipei, Taiwan. Patients with ossicular chain disease and cholesteatoma or inadequate follow-up were excluded. Patients were followed up for 6 months, and final follow-up was completed on January 1, 2016.

Main Outcomes And Measures: The main outcome was the rate of overall graft success after endoscopic transcanal myringoplasty. Secondary outcomes included hearing results and prognostic factors.

Results: The study sample included the medical records of 59 patients (30 men [51%]; 29 women [49%]; mean [SD] age, 49.5 [13.1] years) who underwent endoscopic transcanal myringoplasty. Overall, 55 patients (93%) had a successful graft at 6 postoperative months. The mean (SD) preoperative and postoperative air-bone gaps were 15.9 (9.4) and 5.4 (7.0) dB, respectively, revealing a significant mean (SD) improvement of 10.3 (7.6) dB (Cohen d, 1.27; 95% CI, 0.90-1.63; P < .001, paired t test) in the gap. The postoperative air-bone gap in 46 patients (78%) was less than 10 dB; in 12 patients (20%), 10 to 20 dB; and in 1 patient (2%), more than 20 dB. Postoperative otorrhea significantly affected the graft success rate (odds ratio, 52.00; 95% CI, 4.08-662.55; P < .01, χ2 test). The visualization of the perforation margin (complete or partial) was not significantly associated with the graft success rate. However, partial visualization of the perforation margin significantly prolonged the mean (SD) operative time (complete vs partial, 59.2 [13.7] vs 68.1 [14.1] minutes; Cohen d, 0.64; 95% CI, 0.12-1.18; P = .02, t test).

Conclusions And Relevance: The rate of graft success and hearing outcomes for endoscopic transcanal myringoplasty are comparable with those of microscopic myringoplasty for repairing anterior perforations of the tympanic membrane. However, the present technique is simpler because postauricular incision, canalplasty, and general anesthesia are not required. Thus, endoscopic transcanal myringoplasty should be considered for repairing anterior perforations of the tympanic membrane.
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http://dx.doi.org/10.1001/jamaoto.2016.2114DOI Listing
November 2016

Nasal dissemination of a single-clone IgH-rearranged conjunctival MALT lymphoma through the nasolacrimal duct: A case report.

Oncol Lett 2016 Aug 10;12(2):1007-1010. Epub 2016 Jun 10.

Department of Otolaryngology, Wan Fang Medical Center, Taipei Medical University, Taipei 11698, Taiwan R.O.C.

The aim of the present study was to report a rare case of single-clone, immunoglobulin heavy chain (IgH)-rearranged mucosa-associated lymphoid tissue (MALT) lymphoma in the conjunctiva, with nasal cavity dissemination through the nasolacrimal duct. A 24-year-old female was diagnosed with MALT lymphoma of the nasal cavity at the Department of Otolaryngology, Wan Fang Medical Center, Taipei Medical University (Tapei, Taiwan) in October 2008. A biopsy of the relapsing conjunctival lesion revealed a MALT lymphoma by pathological staining, while a single-clone, IgH-rearranged tumor lesion in the nasal cavity and conjunctiva was confirmed using continuous sinus computed tomography scans and polymerase chain reaction. Tumor lesions were negative for and infection, but exhibited bilateral neck lymph node dissemination. A combination of radiation therapy (a total dosage of 46.8 Gray, in two phases covering the left lacrimal sac, nasal cavity and bilateral neck region) and topical ciprofloxacin plus steroid (0.3% ciprofloxacin 4 times a day and betamethasone eye ointment before sleep for 1 month) was provided as an effective therapeutic strategy, and no recurrence was found in the next 3 years. The nasolacrimal duct serves as a channel for conjunctival tumor spreading and is easily neglected. IgH-involved translocation in MALT lymphoma is a factor in the progression of the disease, and aggressive combination therapy is essential for a high-risk, disseminated IgH-rearranged MALT lymphoma.
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http://dx.doi.org/10.3892/ol.2016.4700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950472PMC
August 2016

Correction: Chan, Y.-Y., et al. The Constituents of Michelia compressa var. formosana and Their Bioactivities. Int. J. Mol. Sci. 2014, 15, 10926-10935.

Int J Mol Sci 2016 May 16;17(5). Epub 2016 May 16.

Department of Chemistry, National Cheng Kung University, Tainan 70101, Taiwan.

The authors wish to make two changes to their published paper [1]. [...].
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http://dx.doi.org/10.3390/ijms17050734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881556PMC
May 2016

Curative-Intent Aggressive Treatment Improves Survival in Elderly Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma and High Comorbidity Index.

Medicine (Baltimore) 2016 Apr;95(14):e3268

From the Biostatistics Center and School of Public Health, Taipei Medical University (J-HC, Y-CY); Institute of Toxicology, College of Medicine, National Taiwan University (S-HL, S-YW); Department of Otorhinolaryngology (S-PY, F-PL, M-TL, C-CW, T-MC, Y-FD); Department of Oral and Maxillofacial Surgery (K-CL); Department of Hemato-Oncology (C-LC, J-MC); Department of Radiation Oncology, Wan Fang Hospital (S-YW); Department of Internal Medicine (J-MC, S-YW), School of Medicine, College of Medicine, Taipei Medical University, Taipei; Department of Biotechnology (S-YW), Hungkuang University, Taichung; Department of Ophthalmology, Buddhist Tzu Chi General Hospital (LLW); Department of Otorhinolaryngology, Taipei Medical University-Shuang Ho Hospital (F-PL), Taipei, Taiwan; and Institute of Biomedical Informatics (H-CY), National Yang Ming University, Taiwan.

For locally advanced head and neck squamous cell carcinoma (HNSCC), therapeutic decisions depend on comorbidity or age. We estimated the treatment outcomes of patients with different Charlson comorbidity index (CCI) scores and ages to determine whether aggressive treatment improves survival.Data from the Taiwan National Health Insurance and cancer registry databases were analyzed, and we included >20-year-old patients with American Joint Committee on Cancer (AJCC) stage III or IV HNSCC (International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0-148.9) undergoing surgery, chemotherapy (CT), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), sequential CT and RT, or surgery with adjuvant treatment. The exclusion criteria were a past cancer history, distant metastasis, AJCC stage I or II, missing sex data, an age < 20 years, nasopharyngeal cancer, in situ carcinoma, sarcoma, and HNSCC recurrence. The index date was the date of first HNSCC diagnosis, and comorbidities were scored using the CCI. The enrolled patients were categorized into Group 1 (curative-intent aggressive treatments) and Group 2 (best supportive care or palliative treatments).We enrolled 21,174 stage III or IV HNSCC patients without distant metastasis (median follow-up, 3.25 years). Groups 1 and 2 comprised 18,584 and 2232 patients, respectively. After adjustment for age, sex, and clinical stage, adjusted hazard ratios (95% confidence intervals) of overall death in Group 1 were 0.33 (0.31-0.35), 0.34 (0.31-0.36), and 0.37 (0.28-0.49), and those of all-cause death among patients undergoing curative surgical aggressive treatments were 1.13 (0.82-1.55), 0.67 (0.62-0.73), and 0.49 (0.46-0.53) for CCI scores of ≥10, 5 to 9, and <5, respectively.Aggressive treatments improve survival in elderly (≥65 years) and critically ill HNSCC patients. Curative nonsurgical aggressive treatments including definitive RT or CCRT might be suitable for HNSCC patients with CCI scores ≥10.
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http://dx.doi.org/10.1097/MD.0000000000003268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998798PMC
April 2016

Outcomes of Induction Chemotherapy for Head and Neck Cancer Patients: A Combined Study of Two National Cohorts in Taiwan.

Medicine (Baltimore) 2016 Feb;95(7):e2845

From the Biostatistics Center and School of Public Health, Taipei Medical University (J-HC, Y-CY); Institute of Toxicology, College of Medicine, National Taiwan University (S-HL, S-YW); Department of Otorhinolaryngology (S-PY, F-PL, M-TL, C-CW, T-MC, Y-FD); Department of Oral and Maxillofacial Surgery (K-CL); Department of Hemato-Oncology (C-LC, J-MC); Department of Radiation Oncology, Wan Fang Hospital (S-YW); Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei (J-MC, S-YW); Department of Biotechnology, Hungkuang University, Taichung (S-YW); Department of Ophthalmology, Buddhist Tzu Chi General Hospital (LLW); and Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan, R.O.C. (S-PY, M-CL); Department of Neurosurgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (M-CL).

The use of induction chemotherapy (CT) is controversial. We compared the survival of head and neck cancer patients receiving docetaxel- or platinum-based induction CT before concomitant chemoradiotherapy (CCRT) with the survival of those receiving upfront CCRT alone. Data from the National Health Insurance and cancer registry databases in Taiwan were linked and analyzed. We enrolled patients who had head and neck cancer between January 1, 2002 and December 31, 2011. Follow-up was from the index date to December 31, 2013. We included head and neck patients diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0-148.9 who were aged >20 years, at American Joint Committee on Cancer clinical cancer stage III or IV, and receiving induction CT or platinum-based CCRT. The exclusion criteria were a cancer history before head and neck cancer diagnosis, distant metastasis, AJCC clinical cancer stage I or II, receipt of platinum and docetaxel before radiotherapy, an age <20 years, missing sex data, docetaxel use during or after RT, induction CT for >8 weeks before RT, induction CT alone before RT, cetuximab use, adjuvant CT within 90 days after RT completion, an RT dose <7000 cGy, curative head and neck cancer surgery before RT, nasopharyngeal cancer, in situ carcinoma, sarcoma, and head and neck cancer recurrence. We enrolled 10,721 stage III-IV head and neck cancer patients, with a median follow-up of 4.18 years (interquartile range, 3.25 years). The CCRT (arm 1), docetaxel-based induction CT (arm 2), and platinum-based CCRT (arm 3; control arm) groups comprised 7968, 503, and 2232 patients, respectively. Arm 3 was used to investigate mortality risk after induction CT. After adjustment for age, sex, clinical stage, and comorbidities, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for overall death were 1.37 (1.22-1.53) and 1.44 (1.36-1.52) in arms 2 and 3, respectively. In a disease-specific survival rate analysis, aHRs (95% CI) of head and neck cancer-related death were 1.29 (1.14-1.46) and 1.47 (1.38-1.56) in arms 2 and 3, respectively. Compared with CCRT alone, docetaxal- or platinum-based induction CT did not improve survival but increased the risk of all-cause and head and neck cancer-related death.
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http://dx.doi.org/10.1097/MD.0000000000002845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998647PMC
February 2016

Dementia Risk in Irradiated Patients With Head and Neck Cancer.

Medicine (Baltimore) 2015 Nov;94(45):e1983

From the Biostatistics Center and School of Public Health, Taipei Medical University (J-HC, Y-CY); Institute of Toxicology, College of Medicine, National Taiwan University (S-HL, S-YW); Department of Otorhinolaryngology (F-PL, M-TL, C-CW, T-MC, S-PY); Department of Oral and Maxillofacial Surgery (K-CL); Department of Hemato-Oncology (C-LC); Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University (S-YW); Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei (S-YW); and Department of Biotechnology, Hungkuang University, Taichung, Taiwan, Republic of China (S-YW).

Patients with head and neck cancer are treated through surgery, radiotherapy (RT), and chemotherapy (CT). Carotid artery damage and neurotoxicity were previously observed in these patients. This study estimated the dementia risk associated with different treatment modalities in a head and neck cancer population with long-term follow-up. Taiwan's National Health Insurance claims database and a cancer registry database from the Collaboration Center of Health Information Application were linked for the present analysis. Patients with head and neck cancer, treated from January 1, 2002 to December 31, 2010, were included in the study. The follow-up duration was the period from the index date to December 31, 2012. Inclusion criteria were head and neck cancer; an age >20 years; and having undergone surgery, CT, concurrent CT, or surgery with adjuvant treatment. Exclusion criteria were another cancer diagnosed before the head and neck cancer, death or being diagnosed with dementia within 2 years after the treatment of the head and neck cancer, stroke before the index date, distant metastasis, in situ carcinoma, sarcoma, head and neck cancer recurrence, an unknown sex, and an age <20 years. In total, 20,135 patients were included. In patient groups that underwent surgery alone, surgery and adjuvant chemoradiotherapy, and chemoradiotherapy alone, the dementia incidence per 1000 person-years was 1.44, 1.04, and 1.98, respectively. The crude hazard ratio (HR) of dementia was 1.84 (95% confidence interval [CI] 1.21-2.81) in the RT with or without CT group. After adjustment for age, sex, clinical stage, and comorbidity, the HR was 1.92 (95% CI 1.14-3.24). Examining the dementia risk in patients who received different treatment modalities according to the Cox proportional-hazard model revealed that an age >65 years and having undergone RT with or without CT were risk factors (P < 0.001 and P = 0.015; and HRs of 16.5 and 1.92, respectively). The dementia risk in patients at different clinical stages was not significantly different among the various treatment groups, regardless of whether the patients received RT. However, younger (<65 y) patients who received RT with or without CT had a 2.96-fold (95% CI 1.24-7.08) higher risk of dementia and a 3.54-fold (95% CI 1.32-9.51) higher adjusted HR compared with the surgery-alone group. Patients who received a total radiation dose >6660 cGy exhibited a 1.69-fold (95% CI 0.97-2.95, P = 0.063) higher dementia risk compared with those who received a total radiation dose <6660 cGy. Receiving a higher radiation dose increased the dementia risk and persistently escalated the dementia incidence even 9 years after RT. Younger (<65 y) patients have a high risk of dementia after RT. The selection of young patients for dose de-escalation requires improvement for reducing irradiation to the neck and areas near brain tissues, particularly in Taiwan, where the median patient age is 53 years.
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http://dx.doi.org/10.1097/MD.0000000000001983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912274PMC
November 2015

Towards an Endpoint Cell Motility Assay by a Microfluidic Platform.

IEEE Trans Nanobioscience 2015 Dec 25;14(8):835-40. Epub 2015 Sep 25.

In vitro cell motility assays are frequently used in the study of cell migration in response to anti-cancer drug treatment. Microfluidic systems represent a unique tool for the in vitro analysis of cell motility. However, they usually rely on using time-lapse microscopy to record the spatial temporal locations of the individual cells being tested. This has created a bottleneck for microfluidic systems to perform high-throughput experiments due to requirement of a costly time-lapse microscopy system. Here, we describe the development of a portable microfluidic device for endpoint analysis of cell motility. The reported device incorporates a cell alignment feature to position the seeded cells on the same initial location, so that the cells' motilities can be analyzed based on their locations at the end of the experiment after the cells have migrated. We show that the device was able to assess cancer cell motility after treatment with a migration inhibitory drug Indole-3-carbinol on MDA-MB-231 breast cancer cells, demonstrating the applicability of our device in screening anti-cancer drug compounds on cancer cells.
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http://dx.doi.org/10.1109/TNB.2015.2455537DOI Listing
December 2015

Trousseau's syndrome in a patient with advanced stage gastric cancer.

World J Gastroenterol 2015 Sep;21(34):10049-53

Tai-Long Chien, Division of Gastroenterology, Department of Internal Medicine, Pin-Tung An-Tai Hospital, Pintung County 92842, Taiwan.

Patients with cancer are at high risk for thrombotic events, which are known collectively as Trousseau's syndrome. Herein, we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery, the left common iliac artery, the posterior tibial artery, and the peroneal artery, which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events, which may correlate with gastric adenocarcinoma. In summary, we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered.
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http://dx.doi.org/10.3748/wjg.v21.i34.10049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566376PMC
September 2015

Association of Single Nucleotide Polymorphisms in the MD-2 Gene Promoter Region With Der p 2 Allergy.

Allergy Asthma Immunol Res 2015 May 5;7(3):249-55. Epub 2015 Mar 5.

Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.; College of Life Sciences, National Chung-Hsing University, Taichung, Taiwan.; Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan.

Purpose: Sensitization to house dust mite (Dermatophagoides pteronyssinus) is a considerable risk factor for the progression of allergic disease. The group 2 allergen from Dermatophagoides pteronyssinus, Der p 2, is considered a major one in patients with specific immunoglobulin E (IgE) to Der p 2. Der p 2 has structural homology with myeloid differentiation 2 (MD-2), which is involved in the lipopolysaccharide-binding component of the Toll-like receptor 4 signaling pathway and the development of inflammation. The aim of this study was to examine the genetic association of single nucleotide polymorphisms (SNPs) in the promoter region of MD-2 with Der p 2-sensitive allergy.

Methods: We investigated associations between cohort's characteristics, including 280 allergic and 80 healthy subjects by examining total IgE, eosinophils, D. pteronyssinus-specific IgE, Der p 2-specific IgE, the number of IgE-producing B cells induced by Der p 2, and the odds ratio of allergic symptoms.

Results: Based on the 1,000 genome project data, the minor allele frequencies of the rs1809441 and rs1809442 are 0.467 and 0.474, respectively. However, the correlation of linkage disequilibrium (LD) between these 2 SNPs is D'=1, the genotype frequencies of the 2 MD-2 (LY96) SNPs (rs1809441 and rs1809442) that are located nearby were significantly different between allergic and health subjects: the TT genotype of rs1809441 and the GG genotype of rs1809442 were more frequent in allergic subjects than in healthy subjects (16.1% vs 2.5% in both genotypes). The allergic patients with these genotypes exhibited significantly higher levels of D. pteronyssinus-specific IgE and Der p 2-specific Ig E, and a larger number of Der p 2-activated B cells. In addition, these 2 SNPs in the MD-2 promoter region were significantly associated with the prevalence of nasal, skin, and asthmatic allergic symptoms.

Conclusions: Our results indicated that 2 SNPs in the MD-2 promoter region were significantly associated with Der p 2-specific Ig E, and thereby suggest that these SNPs may play a major role in susceptibility to Der p 2-triggered immune responses in a Taiwanese population.
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http://dx.doi.org/10.4168/aair.2015.7.3.249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397365PMC
May 2015

Development of a piezoelectric vacuum sensing component for a wide pressure range.

Sensors (Basel) 2014 Nov 21;14(11):22099-112. Epub 2014 Nov 21.

Department of Mechanical Engineering, National Chung Hsing University, 250, Taichung 402, Taiwan.

In this study, we develop a clamped-clamped beam-type piezoelectric vacuum pressure sensing element. The clamped-clamped piezoelectric beam is composed of a PZT layer and a copper substrate. A pair of electrodes is set near each end. An input voltage is applied to a pair of electrodes to vibrate the piezoelectric beam, and the output voltage is measured at the other pair. Because the viscous forces on the piezoelectric beam vary at different air pressures, the vibration of the beam depends on the vacuum pressure. The developed pressure sensor can sense a wide range of pressure, from 6.5 × 10(-6) to 760 Torr. The experimental results showed that the output voltage is inversely proportional to the gas damping ratio, and thus, the vacuum pressure was estimated from the output voltage.
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http://dx.doi.org/10.3390/s141122099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279579PMC
November 2014

The constituents of Michelia compressa var. formosana and their bioactivities.

Int J Mol Sci 2014 Jun 17;15(6):10926-35. Epub 2014 Jun 17.

Department of Chemistry, National Cheng Kung University, Tainan 70101, Taiwan.

Phytochemical investigation of the heartwood of Michelia compressa afforded forty-four compounds, which were identified by comparison of experimental and literature analytical and spectroscopic data. Some compounds were evaluated for their anti-inflammatory and anticancer bioactivities. The result showed that soemerine (1) and cyathisterol (2) exhibited significant nitric oxide (NO) inhibition, with IC50 values of 8.5±0.3 and 9.6±0.5 µg/mL, respectively. In addition, liriodenine (3) and oliveroline (4) exhibited cytotoxicity to human nasopharyngeal carcinoma (NPC-TW01), non-small cell lung carcinoma (NCI-H226), T cell leukemia (Jurkat), renal carcinoma (A498), lung carcinoma (A549) and fibrosarcoma (HT1080) cell lines with IC50 values in the range of 15.7-3.68 μM.
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http://dx.doi.org/10.3390/ijms150610926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100189PMC
June 2014

Detection of haplotype mutations of the MD-2 gene promoter associated with Der p2-induced allergy using a nanostructured biosensor.

Int J Nanomedicine 2014 12;9:1403-12. Epub 2014 Mar 12.

Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.

Group 2 allergens (Der p2) have been reported to be a major cause of the human immune response to dust mite allergens. In this study, we have demonstrated for the first time the effective differentiation between haplotype mutation and normal genes in the MD-2 gene promoter using a nanostructured biosensor. A 70-mer gene fragment containing the haplotype of two single nucleotide polymorphisms in the MD-2 gene promoter region was used as a probe to detect haplotype mutations associated with Der p2-induced allergy. Discrimination was achieved using electrochemical impedance spectroscopy. The discrimination experiments employed 30 haplotype mutation samples and 30 normal target samples. The haplotype mutation samples and normal target samples could be clearly discriminated, even using samples produced by a five-cycle polymerase chain reaction process. The time and cost of sample preparation for the polymerase chain reaction process in the clinical setting can thus be reduced.
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http://dx.doi.org/10.2147/IJN.S59151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3958545PMC
May 2015