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Our previous study showed Tai‐Chi‐Chuan (TCC) training, a moderate exercise, at school improved pulmonary function and inflammation profiles in children with mild asthma. However, habitual practice is hard to maintain with the lack of continuous family and peer support. We investigated whether parental intervention with social media could enhance children's adherence to exercise at home and improve asthmatic outcome measures. Parents were opted to attend a 12‐week TCC classroom training, supervise home practice, and report to a four‐step web‐based social media platform to stay updated and motivated through logging activity and tracking competition. Fractional exhaled nitric oxide (FeNO), FEV1/FVC and peak expiratory flow (PEF) were measured before and after 12 weeks of training. Fifty‐three asthmatic children were allocated into non‐TCC (control, n = 12), TCC groups with moderate‐to‐severe (TCC‐S, n = 26) and mild‐to‐moderate (TCC‐M, n = 15) asthma. We found both TCC groups exhibited better pulmonary function than the non‐TCC control. TCC increased FVC in mild‐to‐moderate asthma children while more pronounced improvement in FEV1, FEV1/FVC, PEF and FeNO was noticed in moderate‐to‐severe asthmatic children. All TCC subjects retained greater participation and better interaction online except for low‐ranking families who dramatically dropped their practice 9 weeks later. For asthmatic children, moderate exercise improves pulmonary functions in a severity‐dependent fashion. Parent‐based Learn‐Practice‐Persuade‐Award wheel is a useful platform to motivate children engagement in physical activity. Classical social persuasive skills could enhance general parent‐child relationship but tend to decrease in persuasiveness over time in low‐ranking families.

Fourier-domain optical coherence tomography (FD-OCT), including spectral-domain OCT (SD-OCT) and swept-source OCT (SS-OCT), allows the volumetric imaging of the tissue architecture with a faster speed and higher detection sensitivity than does time-domain OCT. Although the hardware implementations of SD-OCT and SS-OCT are different, these technologies share very similar signal processing steps for image reconstruction. In this study, we developed hardware implementations and software architectures to design a generic framework for FD-OCT. For SD-OCT systems, an external synchronization approach was used to realize a data acquisition schematic similar to that used in SS-OCT by carefully managing the timing clocks in the detection unit and for the waveform generation. In addition, by utilizing modules and factory concepts, a software engine can be developed that supports various acquisition devices and software operations or image processing functions with high operation flexibility while maintaining its robustness. Data processing and data saving were optimized using the parallel computing method with the OpenMP library and by leveraging the parallelism within the acquired data, respectively.

Background and Aims: Current prediction models for early recurrence of hepatocellular carcinoma (HCC) after surgical resection remain unsatisfactory. The aim of this study was to develop evolutionary learning-derived prediction models with interpretability using both clinical and radiomic features to predict early recurrence of HCC after surgical resection. Methods: Consecutive 517 HCC patients receiving surgical resection with available contrast-enhanced computed tomography (CECT) images before resection were retrospectively enrolled. Patients were randomly assigned to a training set (n = 362) and a test set (n = 155) in a ratio of 7:3. Tumor segmentation of all CECT images including noncontrast phase, arterial phase, and portal venous phase was manually performed for radiomic feature extraction. A novel evolutionary learning-derived method called genetic algorithm for predicting recurrence after surgery of liver cancer (GARSL) was proposed to design prediction models for early recurrence of HCC within 2 years after surgery. Results: A total of 143 features, including 26 preoperative clinical features, 5 postoperative pathological features, and 112 radiomic features were used to develop GARSL preoperative and postoperative models. The area under the receiver operating characteristic curves (AUCs) for early recurrence of HCC within 2 years were 0.781 and 0.767, respectively, in the training set, and 0.739 and 0.741, respectively, in the test set. The accuracy of GARSL models derived from the evolutionary learning method was significantly better than models derived from other well-known machine learning methods or the early recurrence after surgery for liver tumor (ERASL) preoperative (AUC = 0.687, p < 0.001 vs. GARSL preoperative) and ERASL postoperative (AUC = 0.688, p < 0.001 vs. GARSL postoperative) models using clinical features only. Conclusion: The GARSL models using both clinical and radiomic features significantly improved the accuracy to predict early recurrence of HCC after surgical resection, which was significantly better than other well-known machine learning-derived models and currently available clinical models.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumor samples for genomic or drug sensitivity testing is challenging.MethodsCirculating tumor cells (CTCs) were prepared from the liquid biopsies of PDAC patients. These cells were subsequently expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. The CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. CTS was then correlated with clinical response, and analyzed using 2 × 2 contingency tables.ResultsA total of 41 liquid biopsies were collected from 31 patients, with 87.8% of liquid biopsies from patients with Stage 4 disease. CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in surface marker analysis. All patients had received a median of two lines of treatment prior to enrollment, and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts.ConclusionsIn this study, CTCs were expanded from the liquid biopsies of PDAC patients with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach.Trial RegistrationTaipei Medical University Hospital Protocol Record N201803020, registered on July 10, 2018; ClinicalTrials.gov Identifier: NCT04972461, retrospectively registered on July 22, 2021.

Cholangiocarcinoma is the most common primary malignant tumor of the bile duct. The current standard first-line treatment for advanced or metastatic cholangiocarcinoma is gemcitabine and cisplatin. However, few effective treatment choices exist for refractory cholangiocarcinoma, and additional therapeutic drugs are urgently required. Our previous work demonstrated that the ALDH isoform 1A3 plays a vital role in the malignant behavior of cholangiocarcinoma and may serve as a new therapeutic target. In this study, we found a positive correlation between ALDH1A3 protein expression levels and the cell migration abilities of three cholangiocarcinoma cell lines, which was verified using ALDH1A3-overexpressing and ALDH1A3-knockdown clones. We also used ALDH1A3-high and ALDH1A3-low populations of cholangiocarcinoma cell lines from the library of integrated network-based cellular signatures (LINCS) program and assessed the effects of ruxolitinib, a commercially available JAK2 inhibitor. Ruxolitinib had a higher cytotoxic effect when combined with gemcitabine. Furthermore, the nuclear translocation STAT1 and STAT3 heterodimers were markedly diminished by ruxolitinib treatment, possibly resulting in decreased ALDH1A3 activation. Notably, ruxolitinib alone or combined with gemcitabine led to significantly reduced tumor size and weight. Collectively, our studies suggest that ruxolitinib might suppress the ALDH1A3 activation through the JAK2/STAT1/3 pathway in cholangiocarcinoma, and trials should be undertaken to evaluate its efficacy in clinical therapy.

Background and Aims: Immune checkpoint inhibitors (ICIs) exhibit significant clinical activity in patients with advanced hepatocellular carcinoma (HCC). This study explored whether tumor response to ICIs in HCC varies among different organs. Methods: We reviewed the data of patients with advanced HCC who had received ICIs. Patients with measurable diseases were enrolled. Organ-specific response criteria, adapted from RECIST 1.1 and immune-related RECIST, were used to evaluate the objective response to ICIs in tumors located in the liver, lung, lymph node, and other intra-abdominal sites. Results: Of the 75 enrolled patients with advanced HCC, 51 and 11 patients had chronic hepatitis B virus and chronic hepatitis C virus infection, respectively. Regarding ICI treatment, 58, 1, and 16 patients had undergone anti-PD-1/anti-PD-L1 monoclonal antibody (mAb) alone, anti-CTLA4 mAb alone, and anti-PD-1 mAb plus anti-CTLA4 mAb, respectively; 20 and 55 patients had received ICIs as first-line or ≥second-line therapy. The overall objective response rate (ORR) was 28.0%. In total, 58, 34, 19, and 18 patients had measurable hepatic tumors and lung, lymph node, and other intra-abdominal metastases, and the corresponding organ-specific ORRs were 22.4, 41.2, 26.3, and 38.9%, respectively. Of the 39 patients who had both hepatic and extrahepatic tumors, 12 had disease control in extrahepatic tumors while progressive disease (PD) in hepatic tumors, whereas only 4 exhibited disease control in hepatic tumors while PD in extrahepatic tumors (p = 0.046, McNemar test). Of the 16 patients with only evaluable tumors in the liver and lungs at baseline, 8 had disease control in the lungs while PD in the liver, and none experienced disease control in the liver while PD in the lungs (p = 0.005). Conclusions: The hepatic tumors of HCC may be less responsive to ICIs than extrahepatic lesions. Lung metastases responded most favorably to ICIs. The mechanisms underlying this differential response to ICIs warrant further investigation.

Background Remarkable progress has been made in immunotherapy, specifically antibodies for programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1), for treating advanced cancers. In this study, we explored whether circulating immune cells can be used as biomarkers of the efficacy of such therapy. Methods We enrolled patients who received nivolumab, an anti-PD-1 antibody, for advanced hepatocellular carcinoma (HCC) in clinical trials and who consented to the collection of their peripheral blood. Using flow cytometry, we analyzed lymphocyte subclasses and the PD-1 or PD-L1 positivity of immune cells. These results were compared between patients with disease control (complete response, partial response, or stable disease) and those with disease progression. Results This study included 16 patients. The objective response rate was 19%, and the disease control rate was 75%. The hemogram results and the percentage of total αβ T cells or CD4 T cells did not significantly change after nivolumab treatment; moreover, they were not associated with treatment outcomes. The number of CD8 T cells significantly increased after 4 weeks (p = .016); however, this change was not associated with treatment outcomes. Patients with disease control exhibited peripheral B cells with significantly lower pretreatment PD-1 positivity than did patients with disease progression (p = .042). Patients with disease progression were more likely to exhibit monocytes with increased PD-L1 positivity after 28 (p = .020) or 42 (p = .008) days of treatment. Conclusion The low pretreatment PD-1 positivity of peripheral B cells and the constant posttreatment PD-L1 positivity of monocytes were associated with disease control after nivolumab treatment for advanced HCC.

Currently, the cochlear implantation procedure mainly relies on using a hand lens or surgical microscope, where the success rate and surgery time strongly depend on the surgeon’s experience. Therefore, a real-time image guidance tool may facilitate the implantation procedure. In this study, we performed a systematic and quantitative analysis on the optical characterization of ex vivo mouse cochlear samples using two swept-source optical coherence tomography (OCT) systems operating at the 1.06-µm and 1.3-µm wavelengths. The analysis results demonstrated that the 1.06-µm OCT imaging system performed better than the 1.3-µm OCT imaging system in terms of the image contrast between the cochlear conduits and the neighboring cochlear bony wall structure. However, the 1.3-µm OCT imaging system allowed for greater imaging depth of the cochlear samples because of decreased tissue scattering. In addition, we have investigated the feasibility of identifying the electrode of the cochlear implant within the ex vivo cochlear sample with the 1.06-µm OCT imaging. The study results demonstrated the potential of developing an image guidance tool for the cochlea implantation procedure as well as other otorhinolaryngology applications.

Background/Purpose Recent progress in cancer immunology provides more insight in immune evasion of cancer cells. Cancer cells may achieve immune evasion through several ways including ineffective antigen presentation, T cell checkpoint utilization, immunosuppressive cytokines secretion and immunosuppressive cells recruitment. However, few literatures mentioned about the change of peripheral blood immune cells in advanced hepatocellular carcinoma (HCC) patients. To answer this question, we initiated a pilot study through detailed flow cytometry. Methods We enrolled patients with advanced HCC patients who had informed consent to the collection of their peripheral blood. We also recruited healthy individuals for the control group. Using flow cytometry, we analyzed lymphocyte subclasses and the PD-1 or PD-L1 positivity of immune cells in peripheral blood from HCC patients and healthy individuals. Results Twenty-four HCC patients were enrolled and twenty healthy individuals were enrolled. Most of the HCC patients were HBV carrier (58.3%), and the mean age was 61 years old. Among 55 immune cell parameters we examined in peripheral blood, 16 were significantly different between advanced HCC patients and healthy individuals by univariate analysis. Multivariate analysis was then conducted by fitting logistic regression model and showed that CD69−CD25− Naive CD4αβT cell percentage and dendritic cell percentage can reasonably predict the advanced HCC status from peripheral blood. By our regression model, the adjusted generalized R2 = 0.918 and the estimated area under the Receiver Operating Characteristic (ROC) curve was 0.99. Conclusion CD69−CD25− Naive CD4αβT cell percentage and dendritic cell percentage in peripheral blood are highly correlated with the advanced HCC status. The change may result from immune evasion initiated by hepatocellular carcinoma cells and further investigation is warranted. Validation study is ongoing and this mechanism may be utilized to treat advanced HCC patient in the future.

Oral cancer was ranked as the fifth most common cancers in both sexes in Taiwan in 2014. For patients diagnosed with the advanced or late stage of oral SCC, the five-year survival rate is reported to be ~ 33% suggesting the importance of the early detection of oral cancer. There have been various studies of investigating the clinical utility of OCT for the early detection of oral precancerous lesions with 1300 nm OCT technology. In this study, we have developed a long-wavelength, multiscale OCT imaging system enabling multiscale imaging of the ex vivo oral precancerous tissue with an increased imaging depth. Objectives with two different magnifications are mounted to a power turret, enabling seamless change of the OCT imaging resolution via the software control. OCT imaging over a variety of oral precancer pathologies will be demonstrated with above OCT system.

Objective Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although the predictive tool is still unknown. Methods This study aimed to develop a novel gene panel by selecting DNA damage response (DDR) genes from the Catalogue of Somatic Mutations in Cancer (COSMIC) databank and validating them in previously reported cohorts. This association between DDR gene mutations and tumor mutation burden or microsatellite status was analysed from The Cancer Genome Atlas (TCGA) databank. Furthermore, we made the gene panel clinically accessible and predicted the response in clinical patients receiving ICIs by using cell‐free DNA. Results The top 20 mutated DDR genes in various cancers (total 37 genes) were taken from the COSMIC databank, and the DDR genes found to individually predict a response rate > 50% in Van Allen's cohort were selected (Science, 350, 2015 and 207). Eighteen DDR genes were selected as the gene panel. The prevalence and predicted response rate were validated in the other three reported cohorts. Tumor mutational burden‐high was positively associated with mutations of the 18 DDR genes for most cancers. We used cell‐free DNA to test the DDR gene panel and validated by our patients receiving ICIs. This DDR gene panel accounted for approximately 30% of various cancers, achieving a predicted response rate of approximately 60% in patients with a mutated gene panel receiving ICIs. Conclusion This gene panel is a novel and reliable tool for predicting the response to ICIs in cancer patients and guides the appropriate administration of ICIs in clinical practice., Immune checkpoint inhibitors (ICIs) have been widely used to treat various cancers and have achieved impressive success, resulting in a new era of anticancer therapy. However, only a subset of patients experienced lasting responses; therefore, exploring predictive biomarkers is critical to identify the patients who have benefit from ICIs. This gene panel using liquid biopsy is one of the best predictive biomarkers presently available and can help physicians to predict the response to ICIs and judge the utility of ICIs in clinical practice.

Background Gastric cancer tumor markers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), have been applied in clinical practice to screen or monitor treatment responses. However, their sensitivity and specificity are unsatisfactory. Therefore, we assessed the novel tumor marker DR-70 and evaluated its performance in screening and response monitoring. Methods The study included newly diagnosed patients with advanced gastric cancer from March 2012 to October 2015. We measured the DR-70, CEA, and CA 19-9 levels at the time of enrollment. The patients subsequently underwent chemotherapy. We followed-up the patients every 3 months; DR-70 levels and abdominal computed tomography scans were re-evaluated and repeated, respectively, at each follow-up. The correlation between treatment response and DR-70 level after chemotherapy was analyzed. The overall survival and progression-free survival rates were also evaluated. Results A total of 51 patients with gastric cancer were enrolled. Most (82.4%) had metastatic disease. At enrollment, the sensitivity of DR-70 in our study group was 78.4%, compared with 52.9% and 43.1% for CEA and CA 19-9, respectively. When we used the three tumor markers together, the sensitivity increased to 80.4%. We observed a correlation between treatment response and DR-70 level after chemotherapy. No difference in either overall survival or progression-free survival was observed between the DR-70 positive and negative groups. However, a trend toward poorer overall survival was observed for the high DR-70 group, although this was not statistically significant. Conclusion DR-70 is a powerful tool not only for screening unresectable gastric cancer but also for treatment response evaluation.

Background The discovery of effective therapeutic options for treating metastatic poorly differentiated neuroendocrine carcinoma (NEC) after prior platinum-based chemotherapy remains elusive. This study analyzed the efficacy of TLC388 (Lipotecan) Hydrochloride, a novel camptothecin analog, for pretreated patients with metastatic NEC. Methods This single-arm, two-stage, phase II clinical trial was conducted at four community and academic centers in Taiwan. Patients aged 20 years or older with confirmed metastatic NEC and who had received prior systemic therapy with etoposide plus cisplatin were enrolled between July 2015 and May 2018. Patients received 40 mg/m2 of TLC388 intravenously on days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxic effects. Gene mutations were analyzed by next-generation sequencing. Results Twenty-three patients with a median age of 61 (range, 44–73) years, 18 of whom were men (78%), were enrolled. Patients received a median of 2 (range, 0–6) treatment cycles. Among 20 evaluable patients, 3 patients exhibited stable disease and no patient experienced a complete or partial remission, resulting in a disease control rate of 15%. Median progression-free survival was 1.8 (95% confidence interval [CI], 0.4–15) months, and the median overall survival was 4.3 (95% CI, 1.7–15) months. The most common treatment-related hematologic adverse events at grade 3 or higher were leukopenia (22.7%), anemia (31.8%), and thrombocytopenia (18.2%). The most frequent mutated genes in 35 patients with NEC were ARSA, DPYD, HEXB, BRCA1, HPD, MYBPC3, BBS2, IL7R, HSD17B4, and PRODH. Conclusion TLC388 demonstrates limited antitumor activity in metastatic NEC. ClinicalTrials.gov identifier: NCT02457273. Implications for Practice Poorly differentiated neuroendocrine carcinomas (NECs) are rare and aggressive. Currently, effective therapeutic options for treating metastatic poorly differentiated NECs beyond platinum-based chemotherapy remain elusive. In this single-arm, multicenter, phase II study, 23 patients with NEC were enrolled and received TLC388 (Lipotecan) Hydrochloride, which is a novel camptothecin analog. The results demonstrated the disease control rate of 15%, the median progression-free survival of 1.8 (95% confidence interval [CI], 0.4–15) months, and the median overall survival of 4.3 (95% CI, 1.7–15) months. Most importantly, several novel genetic mutations and pathways were identified. These results offer the opportunity to develop future treatment strategies in this rare cancer.

Lessons Learned For patients with advanced hepatocellular carcinoma after failure of first-line sorafenib monotherapy, second-line axitinib provides modest efficacy with tolerable toxicity. The discrepant tumor responses and survival outcomes in trials using axitinib as salvage therapy highlight the importance of optimal patient selection with the aid of clinical biomarkers. Background Multikinase inhibitors have been effective treatment for hepatocellular carcinoma (HCC). This multicenter phase II study explored the efficacy and safety of second-line axitinib for advanced HCC. Methods Patients with advanced HCC and Child-Pugh A liver function, experiencing progression on first-line sorafenib monotherapy, were eligible. Axitinib 5 mg twice daily was given continuously with allowed dose escalation. Tumor assessment was performed according to RECIST version 1.1. The primary endpoint was rate of disease control. Results From April 2011 to March 2016, 45 patients were enrolled. Thirty-seven patients (82%) tested positive for hepatitis B surface antigen. The disease control rate was 62.2%, and the response rate was 6.7%, according to RECIST criteria. Median progression-free survival (PFS) and overall survival (OS) were 2.2 months and 10.1 months, respectively. Treatment-related adverse events were compatible with previous reports of axitinib. Conclusion Second-line axitinib has moderate activity and acceptable toxicity for patients with advanced HCC after failing the first-line sorafenib monotherapy.

We developed a software architecture utilizing the MFC library, allowing OCT imaging/data acquisition in a synchronized fashion. This architecture supports both version of the Fourier-domain OCT frameworks, including the spectral-domain and the swept-source OCT.

Aims Patients with atrial fibrillation (AF) may be at higher risk for cancer, possibly due to the presence of coexisting risk factors. In this study, we investigate the magnitude and predictors of this potential risk within a population-based study. Methods and results The study cohort included 332,555 AF patients aged ≥20 years without past history of cancer. Standardized incidence ratio (SIR) was used as a measure of relative risk, comparing observed cancer incidence among patients with AF with that expected based on cancer incidence in the Taiwanese population. During the observation period, 22,911 incident cancers occurred with an incidence of 1.65%/year. Compared with the general population, AF patients had a significantly higher cancer risk with a SIR of 1.37 (95%CI = 1.36–1.39). Patients with new-onset AF had an elevated cancer risk which was highest within 1 year (SIR = 2.30; 95%CI, 2.25–2.36) and persisted beyond 10 years after AF was diagnosed (SIR = 1.18; 95%CI, 1.11–1.25). Age ≥ 65 years, male gender, hypertension, diabetes, chronic obstructive pulmonary disease (COPD) and liver cirrhosis were significantly associated with development of cancers among AF patients. The hazard ratio of cancers increased from 1.40 (95%CI = 1.28–1.53) for patients having 1 risk factor to 5.14 (95%CI = 4.03–6.06) for patients with 6 risk factors, in comparison to those without any risk factors. Conclusion In the nationwide cohort study, we show that AF patients had a higher risk of cancer. Age, male gender, hypertension, diabetes, COPD and liver cirrhosis are important risk factors of cancer among AF patients. Prompt and detailed examinations may be considered for incident AF patients with multiple risk factors to early detect the occult malignancy.

With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5-year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer.

e15052 Background: Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although predictive biomarkers for efficacy still remain largely unknown. Methods: This study aims to develop a novel gene panel by selecting DNA damage and repair (DDR) genes from the Catalogue of Somatic Mutations in Cancer (COSMIC) database and perform validation using publicly available cohorts. Association between the DDR gene panel and tumor mutation burden or microsatellite status were analyzed from The Cancer Genome Atlas (TCGA) database. To further improve the clinical accessibility of the DDR gene panel, we analyzed the feasibility of its predictive value using cell free DNA in from 64 patients receiving ICIs. Results: The 193 mutated DDR genes in various cancers were chosen from the COSMIC databank, and the DDR genes found to individually predict a response rate > 50% in publicly melanoma cohort (Van Allen, et al) were selected. Eighteen DDR genes were selected as the DDR gene panel. The prevalence of the DDR gene mutations and predicted response rate of ICIs were validated in other three publicly available cohorts (Hugo et al, Synder et al, and Rizvi et al.). Tumor mutational burden and high microsatellite instability were positively associated with mutations of the 18 DDR genes for most cancers. Further validation was performed using cell-free DNA from cancer patients receiving ICIs. This DDR gene panel was detected in approximately 30% of various cancers, achieving a predicted response rate of approximately 60% in patients receiving ICIs. Conclusions: Our developed DDR gene panel can serve as a novel and reliable biomarker that can provide critical information for predicting the response to ICIs in cancer patients and guide the appropriate administration of ICIs in clinical practice.

// Jack P. Wang 1,2,3,* , Chen-Yi Wu 4,5,6,* , Yi-Cheng Yeh 2,7 , Yi-Ming Shyr 2,8 , Ying-Ying Wu 1,2 , Chen-Yu Kuo 1,2,9,10 , Yi-Ping Hung 1,2,4,10 , Ming-Huang Chen 2,10 , Wei-Ping Lee 2,11 , Jiing-Chyuan Luo 1,2 , Yee Chao 1,2,12 and Chung-Pin Li 1,2 1 Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 2 National Yang-Ming University School of Medicine, Taipei, Taiwan 3 Division of Gastroenterology, Department of Internal Medicine, Renai Branch, Taipei City Hospital, Taipei, Taiwan 4 Institute of Public Health, National Yang-Ming University, Taipei, Taiwan 5 Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan 6 Department of Dermatology, Heping Fuyou Branch, Taipei City Hospital, Taipei, Taiwan 7 Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan 8 Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan 9 Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan 10 Division of Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 11 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan 12 Department of Oncology Medicine, Taipei Veterans General Hospital, Taipei, Taiwan * These authors contributed equally to this manuscript Correspondence to: Chung-Pin Li, email: // Keywords : adenocarcinoma; pancreas; erlotinib; epidermal growth factor receptor Received : November 18, 2014 Accepted : May 12, 2015 Published : May 20, 2015 Abstract Objective To analyze the efficacy of gemcitabine with or without erlotinib for pancreatic cancer, and to determine the predictive role of epidermal growth factor receptor ( EGFR ) and KRAS mutations in these patients. Methods This was a single-center, randomized, open-label, prospective trial. Eighty-eight chemotherapy-naive metastatic pancreatic cancer patients were randomized for treatment with gemcitabine or gemcitabine plus erlotinib. EGFR and KRAS mutations were analyzed, respectively. The primary endpoint was the disease control rate. Results Disease control rate (64% vs. 25%; P < 0.001), progression-free survival (median 3.8 vs. 2.4 months; P < 0.001), and overall survival (median 7.2 vs. 4.4 months; P < 0.001) were better in the gemcitabine plus erlotinib group than in the gemcitabine alone group. In the gemcitabine plus erlotinib group, disease control (85% vs. 33%; P = 0.001), progression-free survival (median 5.9 vs . 2.4 months; P = 0.004), and overall survival (median 8.7 vs . 6.0 months; P = 0.044) were better in patients with EGFR mutations than in those without EGFR mutations. KRAS mutation was not associated with treatment response or survival. Conclusions Gemcitabine plus erlotinib is more effective than gemcitabine alone for treating metastatic pancreatic cancer patients, especially those with EGFR mutations. ClinicalTrials.gov number, NCT01608841.

Glint features have important roles in gaze-tracking systems. However, when the operation range of a gaze-tracking system is enlarged, the performance of glint-feature-based (GFB) approaches will be degraded mainly due to the curvature variation problem at around the edge of the cornea. Although the pupil contour feature may provide complementary information to help estimating the eye gaze, existing methods do not properly handle the cornea refraction problem, leading to inaccurate results. This paper describes a contour-feature-based (CFB) 3-D gaze-tracking method that is compatible to cornea refraction. We also show that both the GFB and CFB approaches can be formulated in a unified framework and, thus, they can be easily integrated. Furthermore, it is shown that the proposed CFB method and the GFB method should be integrated because the two methods provide complementary information that helps to leverage the strength of both features, providing robustness and flexibility to the system. Computer simulations and real experiments show the effectiveness of the proposed approach for gaze tracking.

Current evidence suggests potential efficacy of cognitive behavioral therapy for insomnia (CBT-I) in older adults. Mobile applications (apps) have been developed to facilitate CBT-I in the general population. However, because of deteriorating perceptual and cognitive functioning, the effectiveness of mobile apps in older adults remains unknown.This case report aims to demonstrate the utilization, advantages, and limitations of mobile app-assisted CBT-I in an older female adult. An app ("Win-Win aSleep" [WWaS]) was applied in a six-session CBT-I treatment.The patient successfully discontinued her hypnotics and had restored sleep quality after the intervention with WWaS-assisted CBT-I. Several limitations of WWaS were summarized, and pertinent approaches for enhancing future work were discussed.Mobile apps integrating wearable devices might overcome the difficulty for applying WWaS in older adults. In addition to tailored design of mobile technology for older adults, psychosocial support for the utilization of apps may not only enhance the compliance but also provide additional connection to the environment.

Background: Currently, the role of dacarbazine (DTIC) based chemotherapy in neuroendocrine tumors (NETs) in Asia is unclear. Here, we report the outcomes of dacarbazine (DTIC)-based chemotherapy in Taiwan population. Methods: DTIC alone (250 mg/m2/day), or 5-fluorouracil (5-FU, 500 mg/m2/day) and DTIC (200 mg/m2/day) with or without epirubicin (200 mg/m2/day), for 3 days, every 3–4 weeks. Subgroups were analyzed by grading, and by Ki-67 index. Results: 48 patients were reviewed in this study, including 3 had grade 1 tumors, 23 had grade 2, while 22 were grade 3. In grade 3 NEC patients, the tumor Ki-67 index of 21–55% were noted in 8 patients, and >55% in 14 patients. Progression-free survival (PFS) was 5.1 months, and overall survival (OS) was 31.6 months. The PFS (in months) were 12.5 and 1.8 for patients with NETs and neuroendocrine carcinomas (NECs), respectively (p 55%, they were 1.5 and 1.8 months, respectively (p

Insufficient input modality on touchscreens causes icons, toolbars and mode switching steps required to perform different functions. Although various methods are proposed to increase touchscreen input modality, touch gestures (e.g., swipe), usually used in touch input, are not provided in previous methods (e.g., Force Touch on iPhone 6s). This still restricts the input modality on touchscreens. Hence, we propose SegTouch to enhance touch input while providing touch gestures. SegTouch uses thumb-to-index-finger gestures, i.e., the thumb slides on the index finger, to define various touch purposes. Based on a pilot study, the middle and base segments on the index finger are suitable input areas for SegTouch. To observe how users leverage the proprioception and natural haptic feedback from index finger landmarks to perform SegTouch, different layouts on the index finger segments were examined in the eyes-free. Including the normal touch without thumb-to-index-finger gesture, SegTouch provides 9 input modality and touch gestures on the screen, so novel applications are enabled.

Background Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy, and surgical resection remains the only potentially curative treatment. However, the existing literature indicates that those prognostic factors associated with outcome after surgery remain poorly defined. Methods Data were retrospectively collected from 103 patients with ICC who underwent surgical resection between 2005 and 2014. The patients were divided into two groups: one with (D1) and one without (D0) lymph node dissection of hepatic hilum according to the surgery performed. Thereafter, the prognostic values of clinicopathological characteristics were evaluated. Results The median overall survival (OS) after surgical resection of ICC was 43.9 months [95% confidence interval (CI), 11.6–76.2 months]. The 1-, 3-, and 5-year OS rates were 85.5%, 52.8%, and 45.6%, respectively. Multivariable analysis showed that lymph node metastases [hazard ratio (HR), 6.70; 95% CI, 2.18–20.55], positive resection margins (HR, 2.67; 95% CI, 1.14–6.23), periductal infiltration (HR, 3.64; 95% CI, 1.27–10.44), and poor differentiation (HR, 2.90; 95% CI, 1.41–5.95) were independently associated with poor survival. There were no significant differences in clinicopathological characteristics between D1 and D0 groups, except for vascular invasion (p = 0.018) and perineural invasion (p = 0.008). In the D1 group, lymph node metastases were associated with late T stages, multiple tumors, and elevated serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels. Conclusion Regional lymph node metastasis, positive resection margin, periductal infiltration, and poor differentiation were poor prognostic factors in patients with ICC after curative surgery. Lymph node dissection did not show survival benefits, but was useful for nodal staging. However, lymph node metastases were strongly associated with late T stages, multiple tumors, and elevated serum CEA and CA19-9 levels.

BACKGROUND Hepatocellular carcinoma (HCC) is a major complication of hepatitis B virus (HBV) infection. This study investigated the association between nucleos(t)ide analogue (NA) use and the risk of HCC and mortality in HBV carriers on the basis of the Taiwan National Health Insurance Database. METHODS In all, 1544 HBV carriers taking NAs (treated cohort) who were identified between October 1, 2003 and December 31, 2011 were examined for their risk of HCC and mortality; 1544 patients not receiving NA treatment (untreated cohort) were selected via propensity score matching as the comparison group. The risks of first tumor occurrence and mortality were compared. RESULTS The treated cohort had a significantly lower HCC occurrence rate (6.0%; 95% confidence interval [CI], 4.4%-7.9%) in comparison with the untreated cohort (8.5%; 95% CI, 6.6%-10.6%; P = .0025). The overall mortality rates for the treated and untreated cohorts were 6.9% (95% CI, 5.3%-8.7%) and 9.4% (95% CI, 7.7%-11.3%), respectively (P = .0003). After adjustments for competing confounders, Cox regression analyses showed that NA use significantly reduced the risk of HCC (hazard ratio [HR], 0.64; 95% CI, 0.45-0.93; P = .017) and overall mortality (HR, 0.58; 95% CI, 0.43-0.79; P 730 cumulative defined daily doses of NAs, respectively. CONCLUSIONS NA use reduced the risk of HCC and overall mortality in HBV carriers. Cancer 2015;121:1446–1455. © 2014 American Cancer Society.

The treatment of multiple myeloma (MM) has made greatly advances over the last decade, nearly doubling the overall survival time after the use of novel agents such as thalidomide, lenalidomide and bortezomib. However, the improvement of overall survival has occasionally led to clinical scenarios that were rarely recognized before, for example, light chain escape and extramedullary plasmacytoma (EMP). Here we report an MM patient who relapsed and manifested simultaneously with both a light chain escape and a disseminated pattern of EMP after several different modes of treatment, including conventional chemotherapy, autologous peripheral blood stem cell (PBSC) transplantation, and novel agents. The result was disappointing in this case, which taught us several important things: First, intact immunoglobulin may not be a reliable marker in the surveillance of pretreated multiple myeloma. Various tests for renal function, skeletal condition, and serum free light chain should also be carried out for a comprehensive evaluation. Second, EMP remains a tremendous challenge to the clinician, especially when refractory to current novel agents. Further researches are required to clarify the optimal treatment of such a condition in order to help more patients.

Summary Haemostasis is associated with the development and dissemination of cancer. Whether cancer incidence is increased in haemophiliacs remains uncertain; thus, we aimed to further examine this issue. By using data from the National Health Insurance Research Database in Taiwan, we obtained a cohort of 683 patients with haemophilia A, and compared the incidence rate ratio (IRR) of cancer in this cohort with an age- and sex-matched control of 6830 patients. The log-rank test was used to compare Kaplan–Meier curve of the cumulative cancer incidence between two cohorts. Cox regressions were used to identify independent risk factors of cancer in the study patients. The cancer incidence of patients with haemophilia A was significantly higher compared to the control group (IRR 1.95, 95% CI 1.18–3.09, P = 0.008) during the 14-year follow-up period. The non-lymphoma and non-liver cancer incidence in the haemophilia A cohort remained higher than that of the matched control (P = 0.050 by the log-rank test). The multivariate Cox proportional hazards analysis indicated that age (per year, HR 1.09, 95% CI 1.06–1.12, P

This study is aimed to evaluate the cancer risk among patients with coal workers' pneumoconiosis (CWP) using a nationwide population-based dataset. Patients without previous cancer who had been diagnosed with CWP and followed-up for more than 1 year between 1997 and 2006 were recruited from the Taiwan National Health Insurance database. Standardized incidence ratios (SIRs) of cancers in CWP patients were calculated and compared to the cancer incidence in the general population. Risk factors for cancer development were also analyzed. After a median follow-up of 9.68 years, 954 cancers developed among 8,051 recruited CWP patients, with a follow-up of 69,398 person-years. The SIR for all cancers was 1.12 [95% confidence interval (CI) 1.04–1.18]. Males older than 80 years had a SIR of 1.27 (95% CI: 1.06–1.51). The SIRs of esophageal (1.76, 95% CI: 1.24–2.44), gastric (1.42, 95% CI: 1.13–1.76), liver and biliary tract (1.18, 95% CI: 1.01–1.37) and lung and mediastinal (1.45, 95% CI: 1.26–1.66) cancers were significantly higher in the CWP group than in the general population. Multivariate analysis showed that age ≥ 60 years [hazard ratio (HR) 1.70, 95% CI: 1.41–2.05), male gender (HR = 1.79, 95% CI: 1.44–2.23) and liver cirrhosis (HR = 3.99, 95% CI: 2.89–5.51) were significant predictors of cancer development in patients with CWP. We concluded that patients with CWP, especially elderly males, were at increased risk of cancer. Age, male gender and liver cirrhosis were independent risk factors for cancer development.

4101 Background: Therapeutic options for metastatic poorly differentiated neuroendocrine carcinoma (NEC) after prior platinum‐based chemotherapy are unknown. Camptothecin analogs, like topotecan and irinotecan, are approved chemotherapy in small cell lung cancer (SCLC). NEC is considered to have similar biological behavior to SCLC. The aim of this study was to analyze the efficacy of TLC388 (Lipotecan) Hydrochloride, which is a novel camptothecin analog, in pretreated metastatic NEC patients. Methods: This single-arm, 2-stage, phase 2 clinical trial was conducted at 4 community and academic centers in Taiwan. Patients aged 20 years or older enrolled between July 2015 to May 2018 had confirmed metastatic NEC with prior systemic therapy with etoposide plus cisplatin. Patients received intravenous 40 mg/m2 of TLC388 on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxic effects. Results: twenty-three patients with a median age of 61 (range, 44-73) years, including 18 men (78%), were enrolled. Patients received a median of 2 (range, 0-6) treatment cycles. Among 20 evaluable patients, three patients showed a stable disease and no patient a complete or partial remission, resulting in a disease control rate of 15%. Median PFS was 1.8 (95% CI, 0.4-15) months and median OS was 4.3 (95% CI, 1.7-15) months. The most common treatment-related hematologic adverse events at grade 3 or higher were leukopenia (22.7%), anemia (31.8%), and thrombocytopenia (18.2%), respectively. Conclusions: TLC388 shows modest antitumor activity in metastatic NEC. Clinical trial information: NCT02457273.

e15518 Background: Oraxol consists of oral paclitaxel (PTX) administered with the novel P-glycoprotein inhibitor HM30181A which enables the oral absorption of PTX. Ramucirumab (RAM) + intravenous weekly PTX is FDA approved 2nd line treatment of gastric cancer. Oraxol (oral PTX) 200mg/m2 days 1-3, weekly results in similar exposure to weekly 80/m2 intravenous PTX. This phase 1 clinical trial is to determine the maximum tolerated dose (MTD) of Oraxol + RAM. Methods: Eligible patients (pts) have gastric or esophageal cancers and failed prior fluoropyrimidine or platinum containing chemotherapies. Dose escalation followed the standard 3+3 design: Cohort 1: Oraxol 200mg/m2 days 1-3, weekly. Cohort 2: Oraxol 250mg/m2 days 1-3, weekly. Cohort 3: Oraxol 300mg/m2 days 1-3, weekly. Dose of RAM is standard 8 mg/kg IV every 2 weeks. Pts were monitored for dose limiting toxicity (DLT) by week 4. Adverse events (AEs) were assessed per CTCAE v4.03 and response by RECIST v1.1. Results: Cohort 1: One febrile neutropenia (DLT) observed in 6 pts. Partial response (PR) = 2/6, stable disease (SD) = 1/6 and progressive disease (PD) = 3/6 pts. Cohort 2: One grade-3 neutropenia with treatment delay (DLT) in 7 pts. PR = 3/6 and PD = 3/6 in 6 evaluable pts. Cohort 3: One febrile neutropenia (DLT) in 3 pts and study is ongoing. All pts had complete recovery of their DLT. PK showed increase of plasma PTX exposure with dose. Conclusions: The MTD for Oraxol has not been reached yet in combination with RAM. Preliminary results showed that Oraxol + RAM is tolerable and have encouraging anti-tumor activity in gastric or esophageal cancers pts who failed prior chemotherapies. Final results of this study will be presented. Clinical trial information: NCT02970539.

Objective To study the drainage proportions from the corpora cavernosa in defrosted human cadavers, as the veins related to penile erection were recently depicted to comprise the deep dorsal vein (DDV), a pair of cavernous veins (CVs) and two pairs of para-arterial veins (PAVs), as opposed to a single DDV between Buck’s fascia and the tunica albuginea of the human penis. Materials and methods With no formalin fixation, 10 defrosted male human cadavers were used for this study. After injecting a 10% solution of colloid, and with the intracavernous pressure (ICP) fixed at 90 mmHg, the perfusion rate was recorded before and after the DDV, CVs and PAVs were removed, respectively. Finally, measurements were again recorded after penile arterial ligation. Cavernosography was used if required. Results The mean (range) perfusion rate for maintaining the ICP at 90 mmHg was 30.2 (15.5–90.8) mL/min, whereas the arterial perfusion rate was 2.8 (0.3–3.9) mL/min. The mean (range) drainage proportion of the corpora cavernosa was 60.5 (50.3–69.7)%, 11.9 (5.8–22.9)% and 11.4 (5.2–15.0)% via the DDV, CVs and PAVs, respectively. The remaining drainage proportion was 15.6 (14.1–18.1)%. This study shows the separate drainage contributions of the DDV, CVs and PAVs to the corpora cavernosa of the human penis. Conclusion We conclude that the venous drainage system of the corpora cavernosa is much more complex than the previous depictions of it, and the consequent focus on a single DDV. This also shows the independent role of each venous system.

Objective The objective of this study is to assess the incidence and risk of mood disorders, including major depression, anxiety, and bipolar disorders, in Taiwanese patients after the diagnosis of breast cancer compared with a matched cohort. Methods From January 2000 to December 2005, 26,629 newly diagnosed breast cancer patients were enrolled by the Taiwan National Health Insurance program database. The control cohort was selected randomly from 1,000,000 National Health Insurance beneficiaries from a population of 21,400,826 enrolled throughout Taiwan. Each patient was matched with one subject without breast cancer by age, sex, and presence of comorbidities with the same diagnosis index date. The diagnosis of mood disorders was defined by compatible International Classification of Diseases, 9th revision, clinical modification codes plus the prescription of antidepressants for at least 30 days. Results The overall incidence rate ratio of mood disorders was 1.33 (95% CI 1.28–1.39, p

We propose light-weight wearable devices, iKneeBraces, to prevent knee osteoarthritis (OA) using knee adduction moment (KAM) evaluation. iKneeBrace consists of two inertial measurement units (IMUs) to measure shin and thigh angles. KAM is estimated by ground force reaction (GRF), knee position and center of pressure position. Instead of heavy and bulky 3DoF force plates conventionally used, we propose to build a 2D input regression model using shin and thigh angles from iKneeBrace as input to infer GRF direction and further estimate KAM. We perform an experiment to evaluate the method. The results show that iKneeBrace can infer KAM similar to the ground truth in the first peak, the most important part to prevent knee OA. Furthermore, the proposed method can infer KAM in all parts if better IMUs used in iKneeBrace in the future. The proposed method not only makes KAM evaluation portable but also requires only light-weight devices.

Smartphone screen size becomes larger nowadays. However, it causes users hard to reach a target with the thumb when using the smartphone in one hand. We propose an interaction method MovingScreen to solve the hard-to-reach problem by making the smartphone screen view movable. Users move the screen view to make the target into their comfort zone, an area users comfortably performing touch input with the thumb. They then select a target easily. Using the proposed triggering gesture bezel-scroll, MovingScreen automatically calibrates the comfort zone. Bezel-scroll detects the comfort zone and provides different screen moving ratios for users in different poses to hold the smartphone. Users are even allowed to adjust screen moving speed by altering bezel-scroll length. We evaluate performance of MovingScreen and other methods in a user study. The results show that MovingScreen has similar selection time (1030.58ms) but lower error rate (4.57%) to the other methods.

We propose an input device, ThumbRing, for items selection on head-mounted displays (HMDs) or smart glasses. ThumbRing is a ring with an inertial measurement unit (IMU) worn on the thumb to track the motion. By arranging an item to a finger segment, users touch and slide finger segments to select the items. To resist shake in mobile conditions such as walking, another IMU is attached to the back of the hand to compute relative angles between the hand and the thumb. Sliding and touching the segments with the thumb in the hand provide privacy, subtlety, natural haptic feedback and similar input area to smartphones. A pilot study is performed to obtain users' preference finger segments. We evaluate the performance of ThumbRing in different conditions and commitment approaches in a user study. The results show that accuracy are 92.3% and 89.7% in the sitting and walking conditions, respectively.

We propose a finger-worn touch device TouchRing to provide subtle and multi-touch input. TouchRing leverages printed electrodes and the capacitive sensing technique to detect touch input. It allows users to perform multi-touch gestures in one hand to increase input modality. TouchRing worn on the index finger allows multi-touch using the thumb and middle finger. Ten multi-touch gestures are designed in this paper. We also propose touch detection and gesture recognition approaches in TouchRing. Gesture Recognition accuracy is evaluated in the user study. Applications for TouchRing are also proposed to make controlling smart glasses more convenient.

Introduction: To address the issue of limited data on and inconsistent findings for genetic alterations in pancreatic neuroendocrine tumors (pNETs), we analyzed sequences of known pNET-associated genes for their impact on clinical outcomes in a Taiwanese cohort. Methods: Tissue samples from 40 patients with sporadic pNETs were sequenced using a customized sequencing panel that analyzed 43 genes with either an established or potential association with pNETs. Genetic mutations and clinical outcomes were analyzed for potential associations. Results: Thirty-three patients (82.5%) survived for a median 5.9 years (range, 0.3-18.4) of follow up. The median number of mutations per patient was 3 (range, 0-16). The most frequent mutations were in ATRX (28%), MEN1 (28%), ASCL1 (28%), TP53 (20%), mTOR (20%), ARID1A (20%), and VHL (20%). The mutation frequencies in the MEN1 (including MEN1/PSIP1/ARID1A), mTOR (including mTOR/PIK3CA/AKT1/PTEN /TS1/TSC2/ATM), DAXX/ATRX, and angiogenesis (including VHL/ANGPT1/ANGPT2 /HIF1A) pathways were 48%, 48%, 38%, and 45%, respectively. Mutations in ATRX were associated with WHO grade I pNET (vs. grade II or III, p = 0.043), and so were those in genes involved in angiogenesis (p = 0.002). Patients with mutated MEN1 and DAXX/ATRX pathways showed a trend toward better survival, compared to patients with the wild-type genes (p = 0.08 and 0.12, respectively). Conclusion: Genetic profiles of Asian patients with pNETs were distinct from Caucasian patient profiles. Asian patients with pNETs were more frequently mutated for the mTOR and angiogenesis pathways. This could partially explain the better outcome observed for targeted therapy in Asian patients with pNETs.

Thumb-to-fingers interfaces augment touch widgets on fingers, which are manipulated by the thumb. Such interfaces are ideal for one-handed eyes-free input since touch widgets on the fingers enable easy access by the stylus thumb. This study presents DigitSpace, a thumb-to-fingers interface that addresses two ergonomic factors: hand anatomy and touch precision. Hand anatomy restricts possible movements of a thumb, which further influences the physical comfort during the interactions. Touch precision is a human factor that determines how precisely users can manipulate touch widgets set on fingers, which determines effective layouts of the widgets. Buttons and touchpads were considered in our studies to enable discrete and continuous input in an eyes-free manner. The first study explores the regions of fingers where the interactions can be comfortably performed. According to the comfort regions, the second and third studies explore effective layouts for button and touchpad widgets. The experimental results indicate that participants could discriminate at least 16 buttons on their fingers. For touchpad, participants were asked to perform unistrokes. Our results revealed that since individual participant performed a coherent writing behavior, personalized $1 recognizers could offer 92% accuracy on a cross-finger touchpad. A series of design guidelines are proposed for designers, and a DigitSpace prototype that uses magnetic-tracking methods is demonstrated.

Female breast cancer patients have an increased risk of developing subsequent malignant diseases, but this issue is rarely discussed in regards to male breast cancer patients. Thus, we conducted a national survey that included 100,915 female and 578 male breast cancer patients to investigate the risk of second primary malignancy (SPM). During a follow-up period that included 529,782 person-years, 3,153 cases of SPM developed. Compared with the general population, the standardized incidence ratio (SIR) of SPM in breast cancer patients was 1.51 [95% confidence interval (CI): 1.46-1.56]. The observed risk was significantly higher in male patients (SIR 2.17, 95% CI 1.70-2.73) and in patients whose age at breast cancer diagnosis was 40 years or younger (SIR 3.39, 95% CI 2.80-4.07), comparing to age-matched general population. Compared with the overall female population, the SIRs of female breast cancer patients with uterine (SIR: 2.66, 95% CI: 2.37-2.98), thyroid (SIR: 2.30, 95% CI: 2.02-2.62), and bone and soft tissue (SIR: 2.16, 95% CI: 1.56-2.91) cancers were significantly increased. Male breast cancer patients also displayed significantly higher SIRs for thyroid (SIR: 13.2, 95% CI: 1.60-47.69), skin (SIR: 8.24, 95% CI: 3.02-17.94) and head and neck (SIR: 4.41, 95% CI: 2.35-7.54) cancers. Among breast cancer patients, risk factors significantly associated with SPM included male gender, older age, chemotherapy treatment and comorbidity with liver cirrhosis. From our analysis, we concluded that the risk of SPM was significantly higher for both male and female breast cancer patients compared with the general population, suggesting that more intensive surveillance may be needed, especially in high-risk patients.

Background Inpatient palliative care is important for patients with terminal pancreatic cancer. However, the differences between inpatient palliative care and acute hospital care for inpatients with pancreatic cancer have not been explored in a population-based study. Methods This population-based nationwide study was conducted using data from the Taiwan National Health Insurance database to analyze the differences between inpatient palliative care and acute hospital care for inpatients with pancreatic cancer. We identified 854 patients with terminal pancreatic cancer, who had received in-hospital end-of-life care between January 2003 and December 2006. These patients were then sub-divided and matched 1:1 (using propensity score matching) according to whether they received inpatient palliative care (n = 276) or acute hospital care (n = 276). These groups were subsequently compared to evaluate any differences in the use of aggressive procedures, prescribed medications, and medical costs. Results Inpatient palliative care was typically provided by family physicians (39 %) and oncologists (25 %), while acute hospital care was typically provided by oncologists (29 %) and gastroenterologists (24 %). The inpatient palliative care group used natural opium alkaloids significantly more frequently than the acute hospital care group (84.4 % vs. 56.5 %, respectively; P

Background: Immune checkpoints inhibitors (ICIs) such as anti-PD-1/PD-L1 monoclonal antibodies exhibit significant clinical activity in patients with advanced hepatocellular carcinoma (HCC). Immune microenvironments of different organs are often different and may affect the efficacy of immunotherapy. The study explores whether tumor response to ICIs of HCC may vary among different organs. Patients and Methods: We reviewed patients with advanced HCC who had received anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy, alone or in combination, in 3 medical centers in Taiwan. Patients with measurable diseases were enrolled. An organ-specific response criteria, modified from RECIST 1.1, allowing a maximum of 5 measurable lesions per organ system, was used to evaluate the responses to ICIs for tumors of individual organ system. The organ-specific complete responses (CR), partial responses (PR), stable diseases (SD), or progressive diseases (PD) were determined for individual organ system. Results: A total of 76 patients (Male: Female= 62: 14, median age of 59.1 years) with advanced HCC were enrolled. Among them, 51 (67.1%) and 12 (15.8%) patients had chronic hepatitis B virus or chronic hepatitis C infection. The ICI treatments included anti-PD-1 or anti-PD-L1 alone, anti-CTLA4 alone, and anti-PD-1/PD-L1 plus anti-CTLA4 combination in 59, 1, and 16 patients; 20 and 56 patients had received ICIs as first-line or ≥ 2nd-line therapy. The overall response rate (RR) by RECIST 1.1 was 28.9%. Fifty-nine, 34, 18, and 18 patients who had measurable hepatic tumors, lung, lymph node, and intra-abdomen metastases were subject to organ-specific response evaluation. Organ-specific RRs of hepatic tumors, lung, lymph node, and intra-abdomen metastases, were 23.7, 41.2, 27.8, and 38.9%, respectively. Among 39 patients who had both hepatic and extrahepatic tumors, 16 had significant differential responses between hepatic and extrahepatic tumors: 12 of them had disease control (CR/PR/SD) in extrahepatic tumors and PD in hepatic tumors, and 4 exhibited disease control in hepatic tumors and PD in extrahepatic tumors (p=0.046). Moreover, in 16 patients with only evaluable hepatic tumors and lung metastases, 8 had disease control in lung metastases and PD in hepatic tumors, and none experienced disease control in liver tumors and PD in lung metastases (p=0.005). Conclusions: The hepatic tumors of HCC are less responsive to ICIs than the extrahepatic lesions. Lung metastases show best response to ICIs. The underlying mechanism warrants further investigation. (This work is supported by grants from the Ministry of Science and Technology, Taiwan, MOST 106-2314-B-002-210). Citation Format: Li-Chun Lu, Chiun Hsu, Yu-Yun Shao, Yee Chao, Chia-Jui Yen, I-Lun Shih, Yi-Ping Hung, Chun-Jung Chang, Ying-Chun Shen, Jhe-Cyuan Guo, Tsung-hao Liu, Chih-Hung Hsu, Ann-Lii Cheng. Organ-specific differential responses to immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3627.

Background/PurposeConventional training in bronchoscopy may increase patient's discomfort and procedure-related morbidity. Computer-based bronchoscopy simulator (CBBS) permits the acquisition and evaluation of the necessary skills through a realistic bronchoscopic experience. This study was conducted to validate the use of a CBBS system developed in Taiwan as a learning and assessment tool.MethodsTwenty novice bronchoscopists and 10 expert bronchoscopists were enrolled as subjects in this prospective study. The 20 novice bronchoscopists were randomized into two groups, which received conventional bronchoscopic training or CBBS training and then completed a satisfaction survey. Subsequently, the novices who received CBBS training underwent an observational performance trial and the results were compared with those of expert bronchoscopists. All 10 expert bronchoscopists completed a realism survey and observational trial after CBBS performance.ResultsThe satisfaction survey showed that the CBBS training program significantly increased participants' satisfaction (p = 0.002) and interest in learning (p < 0.001). The realism survey by the 10 expert broncho-scopists indicated that CBBS provides a favorable degree of realism with regard to the mechanical and visual parameters examined. Analysis of the performance results showed that the following parameters were capable of differentiating the participants by level of expertise: total procedure time (p = 0.002), percentage of bronchial segments entered (p = 0.012), percentage of bronchial segments identified (p

Objectives The classification of pathological tumor-node-metastasis (pTNM) staging of gastric cancer was revised in the 8th American Joint Committee on Cancer (AJCC) edition. The major revision was the separation of pN3a and pN3b in the pTNM staging. The current study evaluated the prognostic impact of this change. Methods A total of 1,517 patients who underwent curative surgery for gastric cancer with a retrieved lymph node number ≥15 at our institution from January 1995 to December 2011 were enrolled. Survival was compared for the disease classified according to both the 7th and 8th editions. Results After separation of pN3a and pN3b in the pTNM stage definition, the 8th edition still provides significant survival differences between each stage. The multivariate analysis demonstrated that the pTNM stage in both the 7th and 8th editions was an independent prognostic factors of overall survival and disease-free survival. The 8th edition has a better homogeneity than the 7th edition with a significantly higher likelihood ratio chi-square test. Regarding the OS and DFS, the time-dependent receiver operating characteristic (ROC) curves of the two staging systems are almost overlapping, indicating that the prognostic performance is comparable between the two staging systems. Conclusions Both the 7th and 8th edition-based stages are independent prognostic factors for gastric cancer. The 8th edition has a better homogeneity than the 7th edition; the 8th edition provides discriminant survival differences among each pTNM stage that are comparable to those in the 7th edition.

Several studies have reported an increase in second primary malignancies (SPMs) among gastric cancer patients. Patients who were newly diagnosed with gastric cancer between 1997 and 2011 were recruited from the Taiwan National Health Insurance database. Those who had antecedent malignancies or gastrointestinal stromal tumor were excluded. Standardized incidence ratios (SIRs) of SPMs were calculated. Risk factors for cancer development were analyzed by Cox proportional hazards models. Effects of treatments for gastric cancer were treated as time-dependent variables. During the 15-year study period, 47,729 gastric cancer patients were recruited. Overall, 2,110 SPMs developed during a total follow-up of 137,798 person-years. The SIR for all cancers was 1.46. The SIRs for specific follow-up periods were 1.43, 1.41, and 1.21 at >10 years, 5–10 years, and 1–5 years, respectively. After excluding SPMs that developed within 1 year, significantly higher SIRs were seen for cancers of the head and neck (1.34), esophagus (2.16), colon and rectum (1.37), bones and soft tissues (1.95), ovaries (2.89), bladder (1.47), or kidneys (1.44), as well as non-Hodgkin’s lymphoma (5.56). Multivariate analysis showed that age ≥70 years [hazard ratio (HR) 1.19], being male (HR 1.37), diabetes mellitus (HR 1.30), chronic obstructive pulmonary disease (HR 1.17), and liver cirrhosis (HR 1.94) were independent risk factors. Radiotherapy (HR 1.24) and chemotherapy (HR 1.87) were independent risk factors, but surgery (HR 0.67) was not. Patients with gastric cancer are at increased risk of developing SPM. Close surveillance of patients with risk factors over a longer period should be considered.