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National Taiwan University Hospital (NTUH) has demonstrated exceptional resilience and adaptability in its response to the COVID-19 pandemic. Since the outbreak in early 2020, NTUH has been at the forefront of Taiwan's healthcare system, taking proactive measures to prepare for and manage the pandemic. The hospital swiftly established dedicated outpatient clinics and wards, which were crucial in isolating and treating COVID-19 patients. NTUH also played a pivotal role in assisting the government with the development of diagnostic reagents and vaccines and contributing to the global effort to combat the disease. To address the long-term effects of COVID-19, NTUH established a special clinic for integrated care in September 2021, offering physical, occupational, and speech therapy to help patients recover and return to normal life. NTUH also shared its pandemic prevention experience internationally, participating in video conferences to discuss its preventive measures and best practices. In caring for frontline healthcare workers, NTUH established interdisciplinary care teams to provide psychological support, assistance with basic daily needs, and effective social, psychological, and mental health support programs. In conclusion, NTUH demonstrated efficient response capabilities and care for healthcare workers during the COVID-19 pandemic, providing valuable insights for future challenges in dealing with emerging infectious diseases.

Gastric cancer is an inflammation-related cancer triggered by Helicobacter pylori infection. Understanding of the natural disease course has prompted the hypothesis that gastric cancer can be prevented by administering a short-course antibiotic treatment to eradicate the H. pylori infection and interrupt this carcinogenic cascade. Results from randomized controlled trials and cohort studies have repeatedly confirmed this concept, which has moved attention from individual management of H. pylori infection to population-wide implementation of screening programs. Such a paradigm shift follows a three-tier architecture. First, healthcare policy-makers determine the most feasible and applicable eligibility, invitation, testing, referral, treatment, and evaluation methods for an organized screening program to maximize the population benefits and cost-effectiveness. Second, provision of knowledge and effective feedback to frontline general practitioners, including choice of diagnostic tests, selection of eradication regimens, and the indication of endoscopic examination, ensures the quality of care and increases the likelihood of desired treatment responses. Third, initiatives to raise population awareness are designed regarding the impact of H. pylori infection and risky lifestyle habits on the stomach health. These programs, with increased accessibility and geographic coverage in progress, will accelerate the decline in morbidity, mortality, and associated costs of this preventable malignancy.

Background: The need is growing to create medical big data based on the electronic health records collected from different hospitals. Errors for sure occur and how to correct them should be explored. Methods: Electronic health records of 9,197,817 patients and 53,081,148 visits, totaling about 500 million records for 2006–2016, were transmitted from eight hospitals into an integrated database. We randomly selected 10% of patients, accumulated the primary keys for their tabulated data, and compared the key numbers in the transmitted data with those of the raw data. Errors were identified based on statistical testing and clinical reasoning. Results: Data were recorded in 1573 tables. Among these, 58 (3.7%) had different key numbers, with the maximum of 16.34/1000. Statistical differences (P

Abstract Background Serum pepsinogen (PG) is recommended as a screening test for premalignant gastric lesions. However, real-world evidence demonstrating its applicability and equivalence between different test brands is limited. Methods Mass screening began in 2018 in a high-risk Taiwanese population after eradication of Helicobacter pylori, with the first stage of two PG tests (GastroPanel®, Helsinki, Finland and LZ-Test®, Tokyo, Japan) and the second stage of endoscopy. A positive test was defined as PG-I

The treatment of refractory Helicobacter pylori remains challenging in clinical practice. Factors that should be considered in the treatment of refractory H. pylori infection include treatment length, dosage of antibiotics and proton pump inhibitors (PPIs), number of drugs, and the selection of appropriate antibiotics. Extending the treatment length of triple therapy and non-bismuth quadruple therapy to 14 days may increase the eradication rate compared with a shorter period (7 or 10 days). The use of a higher dose of PPIs or vonoprazan may also increase the efficacy of triple therapy. Four-drug therapy, including bismuth or non-bismuth quadruple therapies, usually achieve higher eradication rates than triple therapy. The addition of bismuth or metronidazole to levofloxacin-amoxicillin-PPI therapy may also increase the eradication rate. Therefore, four-drug therapies containing a higher dose of PPIs for 14 days are recommended in the third-line treatment setting for refractory H. pylori infection. The selection of appropriate antibiotics may be guided by susceptibility testing or empirically by medication history. Tailored therapy guided by susceptibility testing or genotypic resistance is recommended whenever possible. However, properly designed empirical therapy based on prior medication history (i.e., avoid the reuse of clarithromycin or levofloxacin empirically) is an acceptable alternative to tailored therapy after considering accessibility, cost, and the preference of the patient.

Abstract The capability of gut microbiota in degrading foods and drugs administered orally can result in diversified efficacies and toxicity interpersonally and cause significant impact on human health. Production of atherogenic trimethylamine N-oxide (TMAO) from carnitine is a gut microbiota-directed pathway and varies widely among individuals. Here, we demonstrated a personalized TMAO formation and carnitine bioavailability from carnitine supplements by differentiating individual TMAO productivities with a recently developed oral carnitine challenge test (OCCT). By exploring gut microbiome in subjects characterized by TMAO producer phenotypes, we identified 39 operational taxonomy units that were highly correlated to TMAO productivity, including Emergencia timonensis, which has been recently discovered to convert γ-butyrobetaine to TMA in vitro. A microbiome-based random forest classifier was therefore constructed to predict the TMAO producer phenotype (AUROC = 0.81) which was then validated with an external cohort (AUROC = 0.80). A novel bacterium called Ihubacter massiliensis was also discovered to be a key microbe for TMA/TMAO production by using an OCCT-based humanized gnotobiotic mice model. Simply combining the presence of E. timonensis and I. massiliensis could account for 43% of high TMAO producers with 97% specificity. Collectively, this human gut microbiota phenotype-directed approach offers potential for developing precision medicine and provides insights into translational research. Video Abstract

Fluoranthene, a high-molecular-weight polycyclic aromatic hydrocarbon (PAH), is widely present in air pollutants, including fine inhalable particulate matter. 3-Bromofluoranthene (3-BrFlu), which is a brominated fluoranthene and halogenated PAH, is generated from waste combustion, metallurgical processes, cement production, e-waste dismantling, and photoreaction. Vascular endothelial cells have key functions in the homeostasis and the development of the cardiovascular system. The zebrafish model has been widely employed to study cardiotoxicity and embryotoxicity. However, no evidence has indicated that 3-BrFlu induces cytotoxicity in vascular endothelial cells, or cardiotoxicity and embryotoxicity in zebrafish. In this study, 3-BrFlu induced concentration-dependent changes in embryo- and cardiotoxicity. Cytotoxicity was also induced by 3-BrFlu in a concentration-dependent manner through apoptosis and necrosis in vascular endothelial cells, SVEC4-10 cells. The activities of caspase-3, -8, and -9 were induced by 3-BrFlu via an intrinsic pathway constituting Bcl-2 downregulation, Bad upregulation, and mitochondrial dysfunction; the extrinsic pathway included the expression of death receptors, including tumour necrosis factor α and Fas receptors. These results indicated that 3-BrFlu caused cardio- and embryotoxicity in zebrafish through vascular endothelial cells cytotoxicity resulting from caspase-dependent apoptosis through intrinsic and extrinsic pathways.

Background/purpose: Although performing balloon enteroscopy soon after the onset of small bowel bleeding appeared to enhance diagnostic rate, the optimal timing was unclear. Methods: A retrospective cohort study in a single referral center. Patients with overt, suspected small bowel bleeding who underwent primary single-balloon enteroscopy (SBE) were evaluated to determine the association between procedure timing and diagnostic yield rates. Results: A total of 220 patients were enrolled (47.7% males; mean age, 65.6 ± 18.1 years). They were stratified into four groups based on the timing of SBE: emergency (7 days (n = 87). A significant trend of decreasing diagnostic yields was observed across the groups (90.6%, 67.9%, 68.3%, and 44.8%, respectively, P 7 days groups (P

Background: Esophageal motility disorders are the major cause of non-obstructive dysphagia (NOD), but may be underdiagnosed. In this high-resolution impedance manometry (HRIM)-based study, we aimed to clarify the etiologies and clinical characteristics of patients presenting with NOD in a Taiwanese population. Methods: From October 2014 to July 2017, consecutive patients with the chief complaint of dysphagia were prospectively enrolled in the study at a tertiary medical center. All subjects underwent a comprehensive diagnostic work-up, which included validated symptom questionnaires, esophagogastroduodenoscopy, timed barium esophagogram, and HRIM. Those with obstructive esophageal lesions were excluded. Esophageal motility disorders were diagnosed using the updated Chicago Classification v3.0. We categorized all patients based on the HRIM results, and compared the clinical characteristics and parameters between groups. Results: A total of 120 patients (55 men; mean age [range], 52 [13–87] years) were analyzed. Achalasia was the most common diagnosis by HRIM (n = 66, 55%), followed by ineffective esophageal motility (n = 15, 12.5%), and absent contractility (n = 6, 5%). Patients with achalasia experienced increased vomiting (62.1% vs. 31.5%, p = 0.001), significant weight loss (22.7% vs. 7.4%, p = 0.025), delayed esophageal emptying (90.9% vs. 12.9%, p

Abstract Background Although fecal hemoglobin concentration (f-Hb) was highly associated with the risk of colorectal neoplasms, current studies on this subject are hampered by skewedness of the data and the ordinal property of f-Hb has not been well studied yet. Our aim was to develop a quantile-based method to estimate adjusted percentiles (median) of fecal hemoglobin concentration and their derived prediction for the risk of multistage outcomes of colorectal disease. Methods We used a 6-year follow-up cohort of Taiwanese nationwide colorectal screening program with fecal immunochemical testing (FIT) to obtain fecal hemoglobin concentration and applied accelerated failure time multi-variable analyses to make the comparison of adjusted median and other percentitles of fecal hemoglobin across four categories of colorectal carcinogenesis. We then predicted the risk of colorectal neoplasms on the basis of the corresponding percentile values by using accelerated failure time model with Bayesian inversion method. Results The adjusted median fecal hemoglobin concentration of nonadvanced adenoma, advanced adenoma, and colorectal cancer were 57, 82, and 163 μg/g feces as opposed to 0 μg/g feces for the normal group. At 90 μg/g of f-Hb, the highly suspected cut-off for colorectal disease, the risks were 17% for non-advanced adenoma, 6% for advanced adenoma, and 9% for CRC. Life-time risks of each colorectal neoplasm were derived by percentiles of fecal hemoglobin concentration. Conclusion Covariate-adjusted risk stratification for multistage outcomes of colorectal neoplasia were provided by using the quantiles of fecal hemoglobin concentration, yielding the estimated life-time risks of 25th to 75th quantitles, ranging from 0.5 to 44% for colorectal cancer, 0.2 to 46% for non-advanced adenoma, and 0.1 to 20% for advanced adenoma.

The complex population of microbes in the human gastrointestinal (GI) tract interacts with itself and with the host, exerting a deep influence on health and disease development. The development of modern sequencing technology has enabled us to gain insight into GI microbes. Helicobacter pylori colonization significantly affects the gastric microenvironment, which in turn affects gastric microbiota and may be correlated with colonic microbiota changes. Crosstalk between H. pylori and GI commensal flora may play a role in H. pylori–related carcinogenicity and extragastric manifestations. We review current knowledge on how H. pylori shapes GI microbiota with a specific focus on its impact on the stomach and colon. We also review current evidence on colonic microbiota changes attributed to eradication therapy based on the clinical studies performed to date.

Background: Whether adjunctive N -acetylcysteine (NAC) may improve the efficacy of triple therapy in the first-line treatment of Helicobacter pylori infection remains unknown. Our aim was to compare the efficacy of 14-day triple therapy with or without NAC for the first-line treatment of H. pylori . Material and methods: Between 1 January 2014 and 30 June 2018, 680 patients with H. pylori infection naïve to treatment were enrolled in this multicenter, open-label, randomized trial. Patients were randomly assigned to receive triple therapy with NAC [NAC-T14, dexlansoprazole 60 mg four times daily (q.d.); amoxicillin 1 g twice daily (b.i.d.), clarithromycin 500 mg b.i.d., NAC 600 mg b.i.d.] for 14 days, or triple therapy alone (T14, dexlansoprazole 60 mg q.d.; amoxicillin 1 g b.i.d., clarithromycin 500 mg b.i.d.) for 14 days. Our primary outcome was the eradication rates by intention to treat (ITT). Antibiotic resistance and CYP2C19 gene polymorphism were determined. Results: The ITT analysis demonstrated H. pylori eradication rates in NAC-T14 and T14 were 81.7% [276/338, 95% confidence interval (CI): 77.5–85.8%] and 84.3% (285/338, 95% CI 80.4–88.2%), respectively. In 646 participants who adhered to their assigned therapy, the eradication rates were 85.7% and 88.0% with NAC-T14 and T14 therapies, respectively. There were no differences in compliance or adverse effects. The eradication rates in subjects with clarithromycin-resistant, amoxicillin-resistant, or either clarithromycin/amoxicillin resistant strains were 45.2%, 57.9%, and 52.2%, respectively, for NAC-T14, and were 66.7%, 76.9%, and 70.0%, respectively, for T14. The efficacy of NAC-T14 and T14 was not affected by CYP2C19 polymorphism. Conclusion: Add-on NAC to triple therapy was not superior to triple therapy alone for first-line H. pylori eradication [ClinicalTrials.gov identifier: NCT02249546].

Abstract Background To develop an individually-tailored dynamic risk assessment model following a multistep, multifactorial process of the Correa’s gastric cancer model. Methods First, we estimated the state-to-state transition rates following Correa’s five-step carcinogenic model and assessed the effect of risk factors, including Helicobacter pylori infection, history of upper gastrointestinal disease, lifestyle, and dietary habits, on the step-by-step transition rates using data from a high-risk population in Matsu Islands, Taiwan. Second, we incorporated information on the gastric cancer carcinogenesis affected by genomic risk factors (including inherited susceptibility and irreversible genomic changes) based on literature to generate a genetic and epigenetic risk assessment model by using a simulated cohort identical to the Matsu population. The combination of conventional and genomic risk factors enables us to develop the personalized transition risk scores and composite scores. Results The state-by-state transition rates per year were 0.0053, 0.7523, 0.1750, and 0.0121 per year from normal mucosa to chronic active gastritis, chronic active gastritis to atrophic gastritis, atrophic gastritis to intestinal metaplasia, and intestinal metaplasia to gastric cancer, respectively. Compared with the median risk group, the most risky decile had a 5.22-fold risk of developing gastric cancer, and the least risky decile around one-twelfth of the risk. The median 10-year risk for gastric cancer incidence was 0.77%. The median lifetime risk for gastric cancer incidence was 5.43%. By decile, the 10-year risk ranged from 0.06 to 4.04% and the lifetime risk ranged from 0.42 to 21.04%. Conclusions We demonstrate how to develop a personalized dynamic risk assessment model with the underpinning of Correa’s cascade to stratify the population according to their risk for progression to gastric cancer. Such a risk assessment model not only facilitates the development of an individually-tailored preventive strategy with treatment for H. pylori infection and endoscopic screening but also provides short-term and long-term indicators to evaluate the program effectiveness.

Background/Purpose: The prevalence of Gastroesophageal reflux disease (GERD) is increasing worldwide, including Asia. Although several consensus reports have been published, little is known regarding the adherence of the physicians on the consensus of GERD. We aimed to survey the agreements and adherence of physicians to the Taiwan GERD consensus before and after the continual medical education (CME) courses. Methods: Two-hundred and twenty-seven physicians, including 81 fellows of gastroenterology, 135 qualified gastroenterologists, and 11 non-gastroenterologist attending physicians were invited to the CME course. Their agreements and adherence to the statements before and after the CME course were assessed by the pre-defined questionnaire with the aid of electronic keypads. The adherence rate before and after the CME course were compared by the McNemar test to indicate the changes in their willingness to follow the statements in clinical practice. Results: The rates of agreement of the 227 participating physicians were uniformly greater than 80% for all of the 22 statements. However, the adherence rates were lower than 80% in 16 statements before the CME intervention. The adherence rates were significantly (p

An alternative screening test is needed to efficiently eradicate Helicobacter pylori from a population with prevalent upper gastrointestinal lesions. We evaluated the performance of a new one-step fecal test for H. pylori for diagnosis of H. pylori infection in Taiwan. Methods: We developed a fecal test to detect H. pylori based on the immunochronomatographic assay and a mixture of monoclonal antibodies. We first recruited symptomatic patients from the primary care setting to evaluate fecal test performance using a reference standard consisting of 13C urea breath test, rapid urease test, and histology. We also compared the performance of the fecal test with that of others. Next, we recruited asymptomatic participants from the mass screening setting to evaluate population attendance for the fecal test and compared its performance with that of 13C urea breath test. Results: In the primary care setting, 117 patients were recruited; H. pylori infection was confirmed in 58 (49.6%). Fecal test sensitivity, specificity, positive and negative predictive values, and accuracy were 88.0% [95% confidence interval (CI): 79.6–96.4%], 100%, 100%, 89.4% (95% CI, 82.0–96.8%), and 94% (95% CI, 89.7–98.3%), respectively. Fecal test specificity and positive predictive value were significantly higher than those of the serological test, whereas the sensitivity and negative predictive value were lower than those of the 13C urea breath test (p

Screening colonoscopy is one of the most effective methods to detect and prevent colorectal cancer by removing neoplastic polyps. The recent discovery of serrated polyps with neoplastic potential has reclassified these polyps into hyperplastic polyps (HPs), sessile serrated adenoma (SSA), and traditional serrated adenoma (TSA) on the basis of macroscopic morphology and microscopic histology. In this study, we aimed to revisit HPs identified during screening endoscopy by histological reevaluation and genetic alterations. Methods: A total of 253 HPs found by screening endoscopy were rechecked by two pathologists, and mutual agreement on the diagnosis of polyps was subjected for further statistical analysis. Direct sequencing for gene mutation at BRAF V600E and KRAS G12D was performed. Results: Among the 253 HPs analyzed, 175 were classified as serrated polyps, while 78 were reclassified into other diagnosis. The concordance among pathologists in diagnosing these serrated polyps was substantial (κ = 0.6672). About 11.5% of the reviewed HPs turned out to be with neoplastic potential, including 7 SSAs, 5 TSAs, as well as 17 conventional adenomas. Results of subgroup analyses revealed that polyps >10 mm were more likely to be found in proximal colon (p = 0.0006) and tended to harbor neoplastic components. We found that two SSAs and one TSA had BRAF mutation, while one TSA had KRAS mutation. The mean size of these mutated adenomas (9.0 mm) was larger than those with wild-type genes (4.9 mm). Conclusion: Serrated polyps with neoplastic potential were prone to be overlooked as hyperplastic and innocent ones during screening colonoscopy. Therefore, both endoscopists and pathologists should pay attention to understand the importance of recognizing serrated adenomas, especially for those polyps >10 mm, or those that are located in the proximal colon.

The prevalence of metabolic syndrome (MS) has increased rapidly in Taiwan and worldwide. We aim to determine the association between sleep-disordered breathing (SDB) and MS in a Chinese general population.This case-control study recruited subjects who have undergone a prospective electrocardiogram-based cardiopulmonary coupling (CPC) sleep spectrogram as part of the periodic health check-ups at the National Taiwan University Hospital. Comprehensive anthropometrics, blood biochemistry, prevalence of MS and its individual components were compared with Bonferroni correction between 40 subjects with SDB, defined as the CPC-derived apnea-hypopnea index (CPC-AHI) >5 event/hour and 80 age- and sex-matched controls, defined as CPC-AHI

Sex differences in response to noxious stimuli or analgesia have been demonstrated. We investigated sex differences in conscious sedation during upper gastrointestinal panendoscopic examination with regard to drug dose and entropy scores. Methods: We investigated sex differences in 30 men and 30 women who were undergoing conscious sedation during upper gastrointestinal panendoscopic examination. The drug mixture was prepared as 5 mg midazolam plus 1 mg alfentanil diluted with normal saline to a volume of 10 mL. An initial injection of 4 mL was followed by an additional 1 mL every 1 minute, until the modified Observer Assessment of Alertness and Sedation (OAAS) rating scale was ≤ 3 when the panendoscope was inserted. Further injection was allowed thereafter. Entropy values, including state entropy (SE) and response entropy (RE), were monitored from baseline to full recovery. Results: The volume of mixture needed to achieve an OAAS score of ≤ 3 was significantly lower in men than in women (4.4 ± 0.7 mL vs. 4.8 ± 0.8 mL, p = 0.034). The initial drug demand was not significantly influenced by age, body weight, or body height. The RE and SE values at the time of panendoscope insertion were not significantly different between men and women. The total volume for men was also significantly lower than that for women (5.7 ± 1.1 mL vs. 6.5 ± 1.4 mL, p < 0.01). The lowest RE and SE values during the procedure were not significantly different between men and women. Conclusion: Women need more analgesic agents than men during panendoscopic examination. There was no significant difference between men and women with regard to anesthetic depth and response to noxious stimuli, as revealed by similar SE and RE values.

Esophageal cancer is ranked as the sixth most common cause of cancer death worldwide and has a substantial effect on public health. In contrast to adenocarcinoma arising from Barrett's esophagus in Western countries, the major disease phenotype in the Asia-Pacific region is esophageal squamous cell carcinoma which is attributed to the prevalence of smoking, alcohol, and betel quid chewing. Despite a multidisciplinary approach to treating esophageal cancer, the outcome remains poor. Moreover, field cancerization reveals that esophageal squamous cell carcinoma is closely linked with the development of head and neck cancers that further sub-optimize the treatment of patients. Therefore, preventive strategies are of paramount importance to improve the prognosis of this dismal disease. Since obstacles exist for primary prevention via risk factor elimination, the current rationale for esophageal cancer prevention is to identify high-risk groups at earlier stages of the disease, and encourage them to get a confirmatory diagnosis, prompt treatment, and intensive surveillance for secondary prevention. Novel biomarkers for identifying specific at-risk populations are under extensive investigation. Advances in image-enhanced endoscopy do not just substantially improve our ability to identify small precancerous or cancerous foci, but can also accurately predict their invasiveness. Research input from the basic sciences should be translated into preventive measures in order to decrease the disease burden of esophageal cancer.

Although evidence suggests that gastroesophageal reflux disease (GERD) may interrupt sleep, the effects of symptomatic and endoscopically diagnosed GERD remain elusive because the patient population is heterogeneous. Accordingly, we designed a cross-sectional study to assess their association. Methods: Consecutive participants in a routine health examination were enrolled. Definition and severity of erosive esophagitis were assessed using the Los Angeles classification system. Demographic data, reflux symptoms, sleep quality and duration, exercise amount, alcohol consumption, and smoking habits were recorded. Factors affecting sleep quality and sleep duration were revealed by a polytomous logistic regression analysis. Results: A total of 3663 participants were recruited. Subjects with reflux symptoms, female gender, higher body mass index, and regular use of hypnotics had poorer sleep quality. Exercise was associated with better sleep quality. Either symptomatically or endoscopically, GERD did not disturb sleep duration. Among the 3158 asymptomatic patients, those with erosive esophagitis were more likely to have poor sleep quality. The risk increased with the severity of erosive changes (p = 0.03). Conclusion: The present study highlights the adverse effect of gastroesophageal reflux on sleep, even in the absence of reflux symptoms. This finding has therapeutic implications in patients with silent erosive disease, and future trials are warranted.

The elderly often seek medical attention because of gastroduodenal diseases. Helicobacter pylori (H. pylori) infection is associated with several gastroduodenal diseases and its prevalence increases with age worldwide. It is estimated that 10–15% of infected patients will have peptic ulcer disease and 1% of patients will have gastric cancer or mucosa-associated lymphoid tissue lymphoma. Notably, the most severe clinical outcomes, i.e., gastric cancer and complicated peptic ulcer diseases, usually occur in elderly patients. Thus the test-and-treatment strategy is not recommended for elderly patients with uninvestigated dyspepsia. However, biopsy specimens for the rapid urease test and histology should be taken from both the antrum and corpus to increase the detection rate in elderly patients, especially in those with atrophic gastritis. The urea breath test may increase the detection rate if the rapid urease test or histology are negative in elderly patients with atrophic gastritis. Standard triple therapy and sequential therapy can achieve satisfactory eradication rates for H. pylori in elderly patients. Elderly patients with peptic ulcers may have a similar benefit from treatment of H. pylori infection as non-elderly patients. Eradication of H. pylori infection may also lead to improvement in histologic grading of gastritis, but the risk of gastric cancer cannot be completely reduced, especially in patients with existing premalignant lesions.

Epidemiological, animal and biological studies provide compelling evidence for the role of Helicobacter pylori infection in gastric carcinogenesis. The finding that H. pylori-induced chronic atrophic gastritis is the major cause of gastric cancer suggests that eradication of the bacterium may prevent this malignancy. Computer-simulation studies have confirmed the cost-effectiveness of eradication in high-risk subjects; however, unresolved issues complicate active testing for and treatment of H. pylori infection among asymptomatic carriers. Concerns include the enormous costs for developing countries to implement strategies, the inconclusiveness of data from randomized controlled studies, the potential induction of antimicrobial resistance, and the uncertain effect of eliminating this organism on the spectrum of modern disease. Although current evidence is insufficient to recommend universal testing and treatment, it is possible to identify highly susceptible individuals who are most likely to benefit from treatment. Novel biomarkers for predicting risk are under extensive investigation, including genetic, epigenetic and proteinomic factors. The emerging evidence suggests that treatment of H. pylori infection in asymptomatic carriers may decrease the burden of gastric cancer. However, confirmation of long-term benefits remains a long way off.

BACKGROUND:Outreach (i.e., to invite those who do not use, or who under use screening services) and inreach (i.e., to invite an existing population who have already accessed the medical system) approaches may influence people to increase their use of screening test; however, whether their outcomes would be equivalent remains unclear. METHODS:A total of 3,363,896 subjects, 50-69 years of age, participated in a colorectal cancer (CRC) screening program using biennial fecal immunochemical tests; 34.5% participated during 2004-2009 when the outreach approach alone was used, and 65.5% participated from 2010-2013 when outreach was integrated with an inreach approach. We compared the outcomes of the two approaches in delivery of screening services. RESULTS:Coverage rates increased from 21.4% to 36.9% and the positivity rate increased from 4.0% to 7.9%, while referral for confirmatory diagnostic examinations declined from 80.0% to 53.3%. The first period detected CRC in 0.20% of subjects screened, with a positive predictive value (PPV) of 6.1%, and the second detected CRC in 0.34% of subjects, with a PPV of 8.0%. After adjusting for confounders, differences were observed in the PPV for CRC (adjusted relative risk, 1.50; 95% confidence interval [CI], 1.41-1.60), cancer detection rate (1.20; 95% CI, 1.13-1.27), and interval cancer rate (0.72; 95% CI, 0.65-0.80). When we focused on the comparison between two approaches during the same study period of 2010-2013, the positivity rate of fecal testing (8.2% vs. 7.6%) and the PPV for CRC detection remained higher (1.07; 95% CI, 1.01-1.12) in subjects who were recruited from the inreach approach. CONCLUSIONS:Outcomes of screening were equivalent or better after integration of outreach and inreach approaches. IMPACT:The results will encourage makers of health-care policy to adopt the integration approach to deliver screening services.

The prevalence of Barrett's esophagus (BE) in Eastern countries is rising to match the prevalence in the West. However, a corresponding trend of BE-associated adenocarcinoma has yet to be observed in Asia. Historically, adenocarcinoma complicating BE has been considered a rare event in Taiwan. In the present report, we collected three Taiwanese cases of esophageal adenocarcinoma arising from BE. The first case was a 37-year-old man with an advanced cancer that developed on pre-existing BE after a 3-year interval without endoscopic surveillance. The second case was a 63-year-old man who presented with odynophagia and was found to have an ulcerative tumor centered on the characteristic Barrett's mucosa. The final case was a 44-year-old man who presented with gradual-onset dysphagia and weight loss, without typical reflux symptom. Our report emphasizes the need for an updated epidemiologic study to determine the incidence of BE-associated adenocarcinoma in Taiwan.

Objective: The advent and utility of new endoscopic imaging modalities for predicting the histology of Barrett’s esophagus (BE) in real time with high accuracy appear promising and could potentially obviate the need to perform random biopsies where guidelines are poorly adhered to. We embarked on evaluating the performance characteristics of white-light endoscopy with magnification (WLE-z), narrow-band imaging with magnification (NBI-z) and a combination of both modalities. Design: This was a prospective online study with 28 endoscopists from 11 countries (Asia-Pacific region) participating as assessors. In total, 35 patients with BE were assessed using 150 slides from WLE-z and NBI-z randomly arranged using a simple classification with corresponding histology. The overall Accuracy (Acc), Sensitivity (Sn), Specificity (Sp), Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of WLE-z, NBI-z and a combination of both were calculated. Results: The overall Acc for WLE-z and NBI-z images was 87.1 % and 88.7 %, respectively. When images from the two modalities were placed side by side, the Acc increased to 90.3 %. The Sn, Sp, PPV, and NPV of WLE-z were 48 %, 92 %, 45 %, and 93 % while with NBI-z, these improved to 89 %, 89 %, 56 %, and 98 %, respectively. When both imaging modalities were viewed together, they improved further to 93 %, 90 %, 61 %, and 99 %. Conclusion: The high NPV (99 %) when both WLE-z and NBI-z were used simultaneously indicates that areas with regular appearance that are diagnosed with confidence can effectively be left alone and not biopsied when performed at a skilled resourced center. This approach could potentially lead to a paradigm shift of how patients with BE are assessed.

The pathogenesis of gastroesophageal reflux disease (GERD) is complex and poorly understood. We aim to investigate the association of various circulating peptide hormones with heterogenous manifestations of GERD.One hundred and four patients that had experienced typical GERD symptoms (heartburn and/or acid regurgitation) for at least 3 episodes per week in the past 3 months were enrolled. All patients received a baseline assessment of symptom severity and frequency with the Reflux Disease Questionnaire and an upper endoscopy to classify GERD into erosive esophagitis (EE, n = 67), non-erosive esophagitis (NE, n = 37), and Barrett's esophagus (BE, n = 8). Fifty asymptomatic subjects with an endoscopically normal esophagus were recruited as the control group. Complete anthropometric measures and blood biochemistry were obtained and fasting serum levels of adipocytokines (adiponectin and leptin) and gut hormones (ghrelin and peptide YY (PYY)) were determined by enzyme-linked immunosorbent assay in all subjects.All circulating peptide hormone levels were not statistically different between the GERD and control groups. However, GERD patients appeared to have lower PYY levels [median (25th-75th percentile), 80.1 (49.8-108.3) vs. 99.4 (65.8-131.9) pg/ml, p = 0.057] compared with control subjects. Among the GERD patients, ghrelin levels were inversely associated with the frequency and severity of acid regurgitation. In male GERD patients, EE was associated with significantly higher PYY levels [107.0 (55.0-120.8) vs. 32.8 (28.7-84.5) pg/ml, p = 0.026] but lower adiponectin levels [6.7 (5.6-9.3) vs. 9.9 (9.6-10.6) μg/ml, p = 0.034] than NE. Patients with BE had significantly lower adiponectin levels [6.0 (5.1-9.2) vs. 9.2 (7.1-11.2) μg/ml, p = 0.026] than those without BE.Humoral derangement of circulating peptide hormones might participate in inflammation and symptom perception in patients suffering from GERD. Further studies to clarify the exact role of these hormones in the pathogenesis of GERD are warranted.

Following a negative test, the performance of fecal immunochemical testing in the subsequent screening round is rarely reported. It is crucial to allocate resources to participants who are more likely to test positive subsequently following an initial negative result.To identify risk factors associated with a positive result in subsequent screening.Dataset was composed of consecutive participants who voluntarily underwent fecal tests and colonoscopy in a routine medical examination at the National Taiwan University Hospital between January 2007 and December 2011. Risk factor assessment of positive fecal test in subsequent screening was performed by using the Cox proportional hazards models.Our cohort consisted of 3783 participants during a 5-year period. In three rounds of subsequent testing, 3783, 1537, and 624 participants underwent fecal tests, respectively; 5.7%, 5.1%, and 3.9% tested positive, respectively, and the positive predictive values were 40.2%, 20.3%, and 20.8%, respectively. Age ≥60 years (adjusted hazard ratio: 1.53, 95% CI: 1.21-1.93) and male gender (1.32, 95% CI: 1.02-1.69) were risk factors; however, an interaction between age and gender was noted. Men had higher risk than women when they were

ObjectiveGastroesophageal reflux disease (GERD) is associated with bothersome symptoms and neoplastic progression into Barrett's esophagus and esophageal adenocarcinoma. We aim to determine the correlation between GERD, esophageal inflammation and obesity with 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).MethodsWe studied 458 subjects who underwent a comprehensive health check-up, which included an upper gastrointestinal endoscopy, FDG PET/CT and complete anthropometric measures. GERD symptoms were evaluated with Reflux Disease Questionnaire. Endoscopically erosive esophagitis was scored using the Los Angeles classification system. Inflammatory activity, represented by standardized uptake values (SUVmax) of FDG at pre-determined locations of esophagus, stomach and duodenum, were compared. Association between erosive esophagitis, FDG activity and anthropometric evaluation, including body mass index (BMI), waist circumference, visceral and subcutaneous adipose tissue volumes were analyzed.ResultsSubjects with erosive esophagitis (n = 178, 38.9%) had significantly higher SUVmax at middle esophagus (2.69±0.74 vs. 2.41±0.57, PConclusionsEsophageal inflammation demonstrated by FDG PET/CT correlates with endoscopic findings and symptomatology of GERD. Obesity markers, both visceral and general, are independent determinants of esophageal inflammation.

Contamination of normal cells is almost always present in tumor samples and affects their molecular analyses. DNA methylation, a stable epigenetic modification, is cell type-dependent, and different between cancer and normal cells. Here, we aimed to demonstrate that DNA methylation can be used to estimate the fraction of cancer cells in a tumor DNA sample, using esophageal squamous cell carcinoma (ESCC) as an example. First, by an Infinium HumanMethylation450 BeadChip array, we isolated three genomic regions (TFAP2B, ARHGEF4, and RAPGEFL1) i) highly methylated in four ESCC cell lines, ii) hardly methylated in a pooled sample of non-cancerous mucosae, a pooled sample of normal esophageal mucosae, and peripheral leukocytes, and iii) frequently methylated in 28 ESCCs (TFAP2B, 24/28; ARHGEF4, 20/28; and RAPGEFL1, 19/28). Second, using eight pairs of cancer and non-cancer cell samples prepared by laser capture microdissection, we confirmed that at least one of the three regions was almost completely methylated in ESCC cells, and all the three regions were almost completely unmethylated in non-cancer cells. We also confirmed that DNA copy number alterations of the three regions in 15 ESCC samples were rare, and did not affect the estimation of the fraction of cancer cells. Then, the fraction of cancer cells in a tumor DNA sample was defined as the highest methylation level of the three regions, and we confirmed a high correlation between the fraction assessed by the DNA methylation fraction marker and the fraction assessed by a pathologist (r=0.85; p

Helicobacter pylori (H. pylori ) are gram-negative bacteria that selectively colonizes the gastric mucosa. The prevalence of H. pylori infection varies from 20 to 50% in industrialized countries to over 80% in developing countries. The infection may persist lifelong without specific treatment. Prolonged infection and inflammation due to bacterial virulence and host genetic factors will lead to chronic gastritis. A certain portion of infected patients then develop more severe pathologies such as peptic ulcer (10—15%), gastric cancer (1%), and mucosa-associated lymphoid tissue lymphoma (