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Background/Aims: Despite the disproportionally high prevalence rates of hepatitis C virus (HCV) amongst the incarcerated population, eradication remains challenging due to logistic and financial barriers. Although treatment prioritization based on disease severity is commonly practiced, the efficacy of such approach remained uncertain. We aimed to compare the impact of unrestricted access to direct-acting antiviral (DAA) among incarcerated HCV-infected patients in Singapore. Methods: In this retrospective study, we reviewed all incarcerated HCV-infected patients treated in our hospital during the restricted DAA era (2013-2018) and unrestricted DAA access era (2019). Study outcomes included the rate of sustained virological response (SVR), treatment completion and treatment default. Subgroup analysis was performed based on the presence of liver cirrhosis, HCV genotype and HCV treatment types. Results: A total of 1,001 HCV patients was followed-up for 1,489 person-year. They were predominantly male (93%) with genotype-3 HCV infection (71%), and 38% were cirrhotic. The overall SVR during the restricted DAA access era and unrestricted DAA access era were 92.1% and 99.1%, respectively. Unrestricted access to DAA exponentially improved the treatment access among HCV-infected patients by 460%, resulting in a higher SVR rate (99% vs. 92%, P=0.003), higher treatment completion rate (99% vs. 93%, P

BACKGROUND AND AIM Real-world data on sofosbuvir/velpatasvir with and without ribavirin (SOF/VEL ± RBV), particularly among patients with genotype 3 (GT3) decompensated cirrhosis, prior treatment, coinfection, and hepatocellular carcinoma (HCC), are scarce. We aimed to assess the efficacy and safety of SOF/VEL ± RBV in a real-world setting that included both community and incarcerated GT3 hepatitis C virus (HCV) patients. METHODS We included all GT3 HCV patients treated with SOF/VEL ± RBV in our institution. The primary outcome measure was the overall sustained virological response 12 weeks after treatment (SVR12), reported in both intention-to-treat (ITT) and per-protocol analyses. The secondary outcome measures were SVR12 stratified by the presence of decompensated cirrhosis, prior treatment, HCC, and HIV/hepatitis C virus coinfection and the occurrence rate of serious adverse events requiring treatment cessation or hospitalization. RESULTS A total of 779 HCV patients were treated with 12 weeks of SOF/VEL ± RBV, of which 85% were treated during incarceration. Among the 530 GT3 HCV patients, 31% had liver cirrhosis, and 6% were treatment-experienced. The overall SVR12 for GT3 was 98.7% (95% confidence interval: 97.3%, 99.5%) and 99.2% (95% confidence interval: 98.1%, 99.8%) in ITT and per-protocol analyses, respectively. High SVR12 was also seen in ITT analysis among GT3 HCV patients with decompensated cirrhosis (88%), prior treatment (100%), HCC (100%), and HIV/hepatitis B virus coinfection (100%). Apart from one patient who developed myositis, no other serious adverse events were observed. CONCLUSION The SOF/VEL ± RBV is a safe and efficacious treatment option for GT3 HCV patients in a real-world setting. SOF/VEL with RBV may be considered for decompensated GT3 HCV patients.

Colonoscopy is a mainstay to detect premalignant neoplastic lesions in the colon. Real-time Artificial Intelligence (AI)-aided colonoscopy purportedly improves the polyp detection rate, especially for small flat lesions. The aim of this study is to evaluate the performance of real-time AI-aided colonoscopy in the detection of colonic polyps.A prospective single institution cohort study was conducted in Singapore. All real-time AI-aided colonoscopies, regardless of indication, performed by specialist-grade endoscopists were anonymously recorded from July to September 2021 and reviewed by 2 independent authors (FHK, JL). Sustained detection of an area by the program was regarded as a "hit". Histology for the polypectomies were reviewed to determine adenoma detection rate (ADR). Individual endoscopist's performance with AI were compared against their baseline performance without AI endoscopy.A total of 24 (82.8%) endoscopists participated with 18 (62.1%) performing ≥ 5 AI-aided colonoscopies. Of the 18, 72.2% (n = 13) were general surgeons. During that 3-months period, 487 "hits" encountered in 298 colonoscopies. Polypectomies were performed for 51.3% and 68.4% of these polypectomies were adenomas on histology. The post-intervention median ADR was 30.4% was higher than the median baseline polypectomy rate of 24.3% (p = 0.02). Of the adenomas excised, 14 (5.6%) were sessile serrated adenomas. Of those who performed ≥ 5 AI-aided colonoscopies, 13 (72.2%) had an improvement of ADR compared to their polypectomy rate before the introduction of AI, of which 2 of them had significant improvement.Real-time AI-aided colonoscopy have the potential to improved ADR even for experienced endoscopists and would therefore, improve the quality of colonoscopy.

Within the past three years, the Singapore government has completed three integrated community hubs around the island. In tandem with the state's decentralization plan of 1991, such large-scale communal architecture plays a significant role in rejuvenating the heartlands and fostering a sense of place as towns mature. These nodal developments leverage on its urban context and programmatic offerings in a bid to generate a sustainable hub ecology for the city. Integrating various national and community stakeholders within a single development might seem like a literal trope for a whole-of-government approach to co-locate, co-share and collaborate. Through Our Tampines Hub, we examine the complexities of Singapore's first integrated hub. While validating the post-occupancy performance of the development, we also re flect and analyse specific design strategies and processes that aid in the social production of this mega community space. Through the theoretical underpinnings of largescale communal architecture as social condensers, this paper seeks to investigate the role and productive potential of this emerging shared urban model of integrated communal architecture in Singapore. It examines not only economic value in the land and space optimization harnessed, but also the new designs produced in the governance framework, closed-loop environmental outcomes and social impetus.

Chronic hepatitis C infection is common among people with history of substance use. Liver fibrosis assessment is a barrier to linkage to care, particularly among those with history of substance users. The use of non-invasive scores can be helpful in predicting liver cirrhosis in the era of HCV elimination, especially in countries where transient elastography (TE) is not available. We compared the commonly used non-invasive scores with a novel non-invasive score in predicting liver cirrhosis in this population.HCV patients with history of substance use between 2011 and 2016 were analyzed. All patients had TE for liver fibrosis assessment. Clinical performance of established non-invasive scores for fibrosis assessment and novel score were compared. Youden's index was used to determine optimal cut-off of the novel score.A total of 579 patients were included. In multivariate logistic regression, cirrhosis on TE was associated with age (P = 0.002), aspartate aminotransferase (AST) (P = 0.004), and platelet count (P 0.001), but not alanine aminotransferase (ALT) (P = 0.896). These form the components of modified AST-to-platelet ratio index (APRI) score. Modified APRI was superior to APRI in predicting cirrhosis (AUROC, 0.796 vs. 0.770, P = 0.007), but not fibrosis-4 score (FIB-4) (P = 1.00). Modified APRI at cut-off of 4 has sensitivity, specificity and negative predictive value (NPV) of 94.4%, 26.9% and 92.6%, respectively, and at 19, has sensitivity, specificity and positive predictive value (PPV) of 33.3%, 96.2% and 77.1%, respectively. FIB-4 has a NPV and PPV of 88.6%, 41.8% and 78.5%, 77.6%, at cut-off of 1.45 and 3.25, respectively. Using the cut-off of 4 and 14 for modified APRI, 32.5% of patients can be correctly classified and misses out only 5.6% of cirrhosis patients.Modified APRI score is superior in predicting cirrhosis in HCV population, with 32.5% of the population being correctly classified using cut-off of 4 and 14. Further studies are required to validate the findings.

Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.

INTRODUCTION AND OBJECTIVES: The novel coronavirus disease 2019 (COVID-19) has affected more than 5 million people globally. Data on the prevalence and degree of COVID-19 associated liver injury among patients with COVID-19 remain limited. We conducted a systematic review and meta-analysis to assess the prevalence and degree of liver injury between patients with severe and non-severe COVID-19. METHODS: We performed a systematic search of three electronic databases (PubMed/MEDLINE, EMBASE and Cochrane Library), from inception to 24th April 2020. We included all adult human studies (>20 subjects) regardless of language, region or publication date or status. We assessed the pooled odds ratio (OR), mean difference (MD) and 95% confidence interval (95%CI) using the random-effects model. RESULTS: Among 1543 citations, there were 24 studies (5961 subjects) which fulfilled our inclusion criteria. The pooled odds ratio for elevated ALT (OR = 2.5, 95%CI: 1.6-3.7, I2 = 57%), AST (OR = 3.4, 95%CI: 2.3-5.0, I2 = 56%), hyperbilirubinemia (OR = 1.7, 95%CI: 1.2-2.5, I2 = 0%) and hypoalbuminemia (OR = 7.1, 95%CI: 2.1-24.1, I2 = 71%) were higher subjects in critical COVID-19. CONCLUSION: COVID-19 associated liver injury is more common in severe COVID-19 than non-severe COVID-19. Physicians should be aware of possible progression to severe disease in subjects with COVID-19-associated liver injury.

Background and aims Availability of transient elastography (TE) limits the application of Baveno-VI criteria. In a derivation study, the ABP criteria (Albumin >40 g/l, Bilirubin 114,000/μl) had been shown to perform well in identifying compensated advanced chronic liver disease (cACLD) patients without high-risk varices (HRV). We aim to externally validate this novel ABP criteria for the exclusion of HRVs among cACLD patients. Methods Data was retrospectively collected from consecutive cACLD patients with paired TE and esophagogastroduodenoscopy (EGD) performed between 2011 and 2017 in Changi General Hospital, Singapore. We estimate the discriminative ability of ABP criteria in validation cohort using AUROC and calibration-in-the-large. We subsequently compare the performance between ABP and Baveno-VI criteria in the validation cohort. Results Among 314 patients included in our validation cohort, 32 (10.2%) had HRV on screening EGD. Application of ABP criteria within this validation cohort has increased discriminative ability than the derivation cohort. The AUROC of validation and derivation cohort were 0.68 (0.60–0.76) and 0.66 (0.60–0.76), respectively. The mean and standard error for calibration-in-the-large and calibration slope were −0.08 (0.22) and 0.93 (0.26) respectively. The ABP criteria had excellent performance in excluding HRV and will spare more screening EGDs than the Baveno-VI criteria (39.2% vs 27.4%, p Conclusion We validated the performance of ABP criteria for the exclusion of HRVs in cACLD patients. ABP criteria is superior to Baveno-VI criteria by sparing more screening EGD without the need of TE.

INTRODUCTION AND AIM Hepatocellular carcinoma (HCC) is a deadly complication among patients with chronic liver disease (CLD). Controversies on the efficacy and safety of statin to prevent HCC among patients with CLD remain despite the growing evidences. We aim to investigate the efficacy and safety of using statin for HCC prevention among adult with CLD. METHODS We performed a systematic search of 4 electronic databases (PubMed/MEDLINE, EMBASE, Cochrane library, and ClinicalTrial.gov) up to April 15, 2020. We selected all types of studies evaluating the statin use and the risk of HCC among CLD patients, regardless of language, region, publication date, or status. The primary endpoint was the pooled risk of HCC. The secondary endpoint was the risk of statin-associated myopathy. RESULT From 583 citations, we included a total of 13 studies (1,742,260 subjects, 7 types of statins), fulfilling the inclusion criteria, evaluating efficacy and safety of statin in CLD patients for HCC prevention. All studies were observational (2 nested case-control studies, 11 cohort studies), and no randomised trial was identified. We found that statin user has a lower pooled risk of HCC development (hazard ratio=0.57, 95% confidence interval: 0.52-0.62, I2=42%). HCC reduction was consistent among statin users in cirrhosis, hepatitis B virus, and hepatitis C virus infections. The risk of statin-associated myopathy was similar between statin user and nonuser (hazard ratio=1.07, 95% confidence interval=0.91-1.27). CONCLUSION Statin use was safe and associated with a lower pooled risk of HCC development among adults with CLD. Given the bias with observation studies, prospective randomised trial is needed to confirm this finding.

Context Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and associated with significant morbidity and mortality. Thyroid hormone (TH) increases β-oxidation of fatty acids and decreases intrahepatic lipid content (IHLC) in rodents with NAFLD. Objective We investigated the possibility of low intrahepatic TH concentration in NAFLD and studied the effect of TH treatment in humans. Design/setting This was a phase 2b single-arm study in six hospitals in Singapore. Intrahepatic thyroid hormone concentrations were measured in rats with induced NAFLD. Patients Euthyroid patients with T2DM and steatosis measured by ultrasonography. Intervention Levothyroxine was titrated to reach a thyroid-stimulating hormone level of 0.34 to 1.70 mIU/L before a 16-week maintenance phase. Main outcome measures The primary outcome measure was change in IHLC measured by proton magnetic resonance spectroscopy after treatment. Results Twenty male patients were included in the per-protocol analysis [mean ± SD: age, 47.8 ± 7.8 years; body mass index (BMI), 30.9 ± 4.4 kg/m2; baseline IHLC, 13% ± 4%]. After treatment, IHLC was decreased 12% (±SEM, 26%) relative to baseline (absolute change, -2%; 95% CI, -3 to 0; P = 0.046). Small decreases in BMI (P = 0.044), visceral adipose tissue volume (P = 0.047), and subcutaneous adipose tissue volume (P = 0.045) were observed. No significant changes in glucose regulation or lipid profile occurred. Conclusion This study demonstrated the efficacy and safety of low-dose TH therapy for NAFLD in men. TH or TH analogs may be beneficial for this condition.

Background Diabetes mellitus is associated with inadequate delivery of oxygen to tissues. Cellular hypoxia is associated with mitochondrial dysfunction which increases oxidative stress and hyperglycaemia. Hyperbaric oxygenation therapy, which was shown to improve insulin sensitivity, is impractical for regular use. We evaluated the effects of water which is stably-enriched with oxygen (ELO water) to increase arterial blood oxygen levels, on mitochondrial function in the presence of normal- or high-glucose environments, and as glucose-lowering therapy in humans. Methods We compared arterial blood oxygen levels in Sprague-Dawley rats after 7 days of ad libitum ELO or tap water consumption. Mitochondrial stress testing, and flow cytometry analysis of mitochondrial mass and membrane potential, were performed on human HepG2 cells cultured in four Dulbecco’s Modified Eagle Medium media, made with ELO water or regular (control) water, at normal (5.5 mM) or high (25 mM) glucose concentrations. We also randomized 150 adults with type 2 diabetes (mean age 53 years, glycated haemoglobin HbA1c 8.9% [74 mmol/mol], average duration of diabetes 12 years) to drink 1.5 litres daily of bottled ELO water or drinking water. Results ELO water raised arterial oxygen tension pO2 significantly (335 ± 26 vs. 188 ± 18 mmHg, p = 0.006) compared with tap water. In cells cultured in control water, mitochondrial mass and membrane potential were both significantly lower at 25 mM glucose compared with 5.5 mM glucose; in contrast, mitochondrial mass and membrane potential did not differ significantly at normal or high glucose concentrations in cells cultured in ELO water. The high-glucose environment induced a greater mitochondrial proton leak in cells cultured in ELO water compared to cells cultured in control medium at similar glucose concentration. In type 2 diabetic adults, HbA1c decreased significantly (p = 0.002) by 0.3 ± 0.7% (4 ± 8 mmol/mol), with ELO water after 12 weeks of treatment but was unchanged with placebo. Conclusions ELO water raises arterial blood oxygen levels, appears to have a protective effect on hyperglycaemia-induced reduction in mitochondrial mass and mitochondrial dysfunction, and may be effective adjuvant therapy for type 2 diabetes.

Aims Advanced fibrosis (AF) and liver cirrhosis (LC) are important milestones in non-alcoholic fatty liver disease (NAFLD). FIB-4, NFS and BARD are validated scores with good accuracy in detecting AF and LC. APRI does not have similar predictive accuracy. While a modification (m-APRI) improves its use in viral hepatitis, this has yet to be evaluated in NAFLD. This study compares diagnostic performance of aforementioned scores in predicting AF and LC in NAFLD. Methods Consecutive NAFLD patients undergoing Transient Elastography (TE) using Echosens® Fibroscan® for fibrosis staging were included. Cut-off liver stiffness measurements for AF and LC were 7.9 kPa and 11.5 kPa respectively. Anthropometric and laboratory tests done within 3 months were used. Diagnostic performances of scores were analyzed by standard statistical tests. Results 161 patients qualified for the study. Mean age was 60.2 ± 14 years, BMI 26.8 ± 4.6 kg/m2. M-probe was used in 113, XL in 48. Optimal cut-offs of m-APRI for AF and LC were 5.84 and 9 respectively. Area under receiver operator characteristic curves (AUROC) for prediction of AF at optimal cut-off points were m-APRI 0.84, APRI 0.80, FIB-4: 0.77, NFS 0.77 and BARD 0.65. For prediction of LC, AUROC were m-APRI: 0.83, APRI: 0.76, FIB-4: 0.81, NFS: 0.77 and BARD: 0.66. m-APRI was significantly superior to all scores compared in detecting AF (p Conclusions For prediction of AF in NAFLD, m-APRI outperforms BARD, APRI, NFS and FIB-4, while for the prediction of cirrhosis, m-APRI is superior to APRI and BARD but comparable to NFS and FIB-4.

Background and study aims Published data on blue laser imaging (BLI) for detection and differentiation of colonic polyps are limited compared to narrow band imaging (NBI). This study investigated whether BLI can increase the detection rate of colonic polyps and adenomas when compared to white light imaging (WLI), and examined use of NICE (NBI International Colorectal Endoscopic) and JNET (Japan NBI Expert Team) classifications with BLI. Patients and methods Patients aged 50 years and above referred for colonoscopy were randomized to BLI or WLI on withdrawal. Detected polyps were characterized using NICE and JNET classifications under BLI mode and correlated with histology. Primary outcome was adenoma detection rate. Secondary outcomes were utility of NICE and JNET classifications to predict histology using BLI. Results A total of 182 patients were randomized to BLI (92) or WLI (90). Comparing BLI with WLI, the polyp detection rate was 59.8 % vs 40.0 %, P = 0.008, and the adenoma detection rate was 46.2 % vs 27.8 %, P = 0.010. NICE 1 and JNET 1 diagnosed hyperplastic polyps with sensitivity of 87.18 % and specificity of 84.35 %. NICE 2 diagnosed low- (LGD) or high-grade dysplasia (HGD) with sensitivity of 92.31 % and specificity of 77.45 %. JNET 2A diagnosed LGD with sensitivity of 91.95 %, and specificity of 74.53 %. Four cases of focal HGD all had JNET 2A morphology. Conclusion BLI increased adenoma detection rate compared to WLI. NICE and JNET classifications can be applied when using BLI for endoscopic diagnosis of HP and LGD but histological confirmation remains crucial.

Introduction Endoscopic submucosal dissection (ESD) provides a higher en bloc and R0 resection rate than endoscopic mucosal resection. Colorectal ESD is not widely used because of its technical difficulty and risk of complications, especially for right-sided colonic lesions. We audited the clinical outcomes of our initial experience with colorectal ESD. Methods We reviewed data collected from a prospective registry of patients who underwent colorectal ESD from December 2014 to March 2018. Therapeutic outcomes and procedure-related complications were analysed. Results A total of 41 patients (mean age 67.4 years, 21 male) underwent colorectal ESD. The distribution of the lesions was as follows: rectum (n = 9), sigmoid colon (n = 8), descending colon (n = 6), splenic flexure (n = 1), transverse colon (n = 5), ascending colon (n = 8) and caecum (n = 4). The mean size was 23 (range 12-50) mm. En bloc resection was achieved in 35 (85.4%) out of 41 patients, and R0 resection or clear resection margins was achieved in 33 (94.3%) of the en bloc resection patients. The lesion was upstaged in 14 (34.1%) patients after ESD. Colonic perforation occurred in 3 (7.3%) patients during ESD and was successfully treated with endoscopic clips. There was no procedure-related bleeding. No patient required surgery for management of complications. The median duration of hospitalisation was 1 (range 0-7) day. Four patients with lesions that were upstaged after ESD, from high-grade dysplasia to intramucosal carcinoma with deep submucosal invasion, were referred for colectomy. Conclusion Our early outcome data was comparable to that from large published series. ESD is an effective and feasible treatment for colorectal lesions.

Introduction Spontaneous bacterial peritonitis (SBP) is the commonest complication of liver cirrhosis. Timely and appropriate treatment of SBP is crucial, particularly with the rising worldwide prevalence of multidrug-resistant organisms (MDROs). We aimed to investigate the clinical outcomes of SBP in Singapore. Methods All cirrhotic patients with SBP diagnosed between January 2014 and December 2017 were included. Nosocomial SBP (N-SBP) was defined as SBP diagnosed more than 48 hours after hospitalisation. Clinical outcomes were analysed as categorical outcomes using univariate and multivariate analysis. Results There were 33 patients with 39 episodes of SBP. Their mean age was 64.5 years and 69.7% were male. The commonest aetiology of cirrhosis was hepatitis B (27.3%). The Median Model for End-stage Liver Disease (MELD) score was 17; 33.3% had acute-on-chronic liver failure and 60.6% had septic shock at presentation. N-SBP occurred in 25.6% of SBP cases. N-SBP was more commonly associated with MDROs, previous antibiotic use in the past three months (p = 0.014) and longer length of stay (p = 0.011). The 30-day and 90-day mortality among SBP patients was 30.8% and 51.3%, respectively. MELD score > 20 was a predictor for 30-day mortality. N-SBP and MELD score > 20 were predictors for 90-day mortality. Conclusion N-SBP was significantly associated with recent antibiotic use, longer hospitalisation, more resistant organisms and poorer survival among patients with SBP. N-SBP and MELD score predict higher mortality in SBP. Judicious use of antibiotics may reduce N-SBP and improve survival among cirrhotic patients.

Background Antibiotic resistance is an important cause of H. pylori treatment failure. This study aimed to examine the change in H. pylori antibiotic resistance profile in Singapore over the course of 15 years. Materials and methods The study period was from 2000 to 2014. Gastric mucosal biopsies obtained from H. pylori-positive patients were cultured. Antibiotic susceptibility to metronidazole, clarithromycin, levofloxacin, tetracycline, and amoxicillin was tested. The change in resistance rates over time was analyzed. Results A total of 708 H. pylori isolates were cultured. There was a significant increase in resistance rates for metronidazole (2000–2002: 24.8%; 2012–2014: 48.2%; p < .001), clarithromycin (2000–2002: 7.9%; 2012–2014: 17.1%; p = .022), and levofloxacin (2000–2002: 5%; 2012–2014: 14.7%; p = .007). The resistance rates for tetracycline (2000–2002: 5%; 2012–2014: 7.6%) and amoxicillin (2000–2002: 3%; 2012–2014: 4.4%) remained stable. Increase in dual (2000–2002: 6.9%; 2012–2014: 9.4%; p = .479) and triple antibiotic resistance rates (2000–2002: 0; 2012–2014: 7.6%; p < .001) were observed. Overall, the most common dual and triple resistance patterns were metronidazole/clarithromycin (4.4%) and metronidazole/clarithromycin/levofloxacin (1.8%), respectively. Conclusions Over 15 years, H. pylori resistance rates to metronidazole, clarithromycin and levofloxacin had increased. There was increased resistance to multiple antibiotics.

Narrow band imaging (NBI) is generally considered to be useful for lesion characterization, but not enhanced detection of gastric lesions, because of the dark endoscopic view. We tested whether the new generation of NBI (190-NBI or 290-NBI), which is twice as bright as the previous version, would improve detection of premalignant gastric lesions compared with high-definition white light endoscopy (HD-WLE).This was a multicenter prospective randomized study involving five tertiary institutions in the Asia-Pacific region. A total of 579 patients aged older than 50 years who underwent diagnostic upper gastrointestinal endoscopy were randomized to either HD-WLE or NBI. The outcome measurements were detection of intestinal metaplasia (IM), focal gastric lesions, and gastric cancers.Focal gastric lesions were detected in 83/286 (29%) and 119/293 patients (40.6%) by HD-WLE and by NBI, respectively (P=0.003). IM was detected in 22/286 patients (7.7%) by HD-WLE and in 52/293 patients (17.7%) by NBI (P0.001). Gastric cancer were found in 7/286 (2.4%) and 3/293 patients (1%) in HD-WLE and NBI groups, respectively (P=0.189).NBI increased the detection rate of IM compared with HD-WLE.

Background and Aims Wire-guided biliary cannulation has been demonstrated to improve cannulation rates and reduce post-ERCP pancreatitis (PEP), but the impact of wire caliber has not been studied. This study compares successful cannulation rates and ERCP adverse events by using a 0.025-inch and 0.035-inch guidewire. Methods A randomized, single blinded, prospective, multicenter trial at 9 high-volume tertiary-care referral centers in the Asia-Pacific region was performed. Patients with an intact papilla and conventional anatomy who did not have malignancy in the head of the pancreas or ampulla and were undergoing ERCP were recruited. ERCP was performed by using a standardized cannulation algorithm, and patients were randomized to either a 0.025-inch or 0.035-inch guidewire. The primary outcomes of the study were successful wire-guided cannulation and the incidence of PEP. Overall successful cannulation and ERCP adverse events also were studied. Results A total of 710 patients were enrolled in the study. The primary wire-guided biliary cannulation rate was similar in 0.025-inch and 0.035-inch wire groups (80.7% vs 80.3%; P = .90). The rate of PEP between the 0.025-inch and the 0.035-inch wire groups did not differ significantly (7.8% vs 9.3%; P = .51). No differences were noted in secondary outcomes. Conclusion Similar rates of successful cannulation and PEP were demonstrated in the use of 0.025-inch and 0.035-inch guidewires. (Clinical trial registration number: NCT01408264.)

There is no consensus on what constitutes adequate training for needle knife precut sphincterotomy.The purpose of this study was to determine the number of procedures required before effective and safe precut sphincterotomy can be achieved.This retrospective study examined the cumulative experience of a single endoscopist from January 2006-December 2015. Precut sphincterotomy success and complication rates were analyzed as a function of number of procedures performed. Acceptable success and complication rates were defined as 85% and 10% respectively. A one-sided binomial test was used to test success and complication rates of every 25 precut sphincterotomies performed.The index endoscopic retrograde cholangiopancreatography was successful in 141/158 (89.2%) patients who underwent precut sphincterotomy. This increased to 148/158 (93.7%) when endoscopic retrograde cholangiopancreatography was repeated on another day. Six precut sphincterotomies were required to achieve an 85% success probability. This was maintained consistently above 85% after 13 precuts, and was significantly higher (91.2%;At least 13 precut sphincterotomies were required to achieve a sustained success rate greater than 85%. The probability of bleeding or pancreatitis was less than 5% after 50 precut sphincterotomies.

Introduction Endoscopic transenteric stenting is the standard treatment for pseudocysts, but it may be inadequate for treating infected collections with solid debris. Surgical necrosectomy results in significant morbidity. Direct endoscopic necrosectomy (DEN), a minimally invasive treatment, may be a viable option. This study examined the efficacy and safety of DEN for the treatment of infected walled-off pancreatic necrosis and infected pseudocysts with solid debris. Methods This study was a retrospective analysis of data collected from a prospective database of patients who underwent DEN in the presence of infected walled-off pancreatic necrosis or infected pseudocysts with solid debris from April 2007 to October 2011. DEN was performed as a staged procedure. Endoscopic ultrasonography-guided transgastric stenting was performed during the first session for initial drainage and to establish endoscopic access to the infected collection. In the second session, the drainage tract was dilated endoscopically to allow transgastric passage of an endoscope for endoscopic necrosectomy. Outcome data included technical success, clinical success and complication rates. Results Eight patients with infected walled-off pancreatic necrosis or infected pseudocysts with solid debris (mean size 12.5 cm; range 7.8-17.2 cm) underwent DEN. Underlying aetiologies included severe acute pancreatitis (n = 6) and post-pancreatic surgery (n = 2). DEN was technically successful in all patients. Clinical resolution was achieved in seven patients. One patient with recurrent collection opted for surgery instead of repeat endotherapy. No procedural complications were encountered. Conclusion DEN is a safe and effective minimally invasive treatment for infected walled-off pancreatic necrosis and infected pseudocysts.

Objective This study was aimed to assess whether the efficacy of one-week triple therapy comprising of proton pump inhibitor, amoxicillin and clarithromycin (PPI/A/C) on Helicobacter pylori (H. pylori) infection in Singapore has decreased over the duration from 2005 to 2010. Methods The clinical data of H. pylori-positive patients treated with one-week PPI/A/C in 2005 and 2010 were reviewed retrospectively using a registry database. The primary endpoint was the difference in treatment success rate. Results A total of 465 patients (n = 174 in 2005 and n = 291 in 2010) were analyzed. In 2010, compared with 2005, the mean age of patients was younger (47 vs 56 years, P

BackgroundPatients with recurrent nonvariceal upper gastrointestinal bleeding who have failed endoscopic therapy pose a challenge. Percutaneous transcatheter angiographic embolization (TAE) is an alternative to surgery but remains controversial. This study compares the treatment outcomes in patients

BACKGROUND AND AIMS Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced procedure with significant complication rate of 5 to 10%. Scant data is available on quality indicators for trainee-involved ERCP. In our study, we evaluated the outcome of trainee-involved ERCPs in which a protocol-based strategy to minimize complications during selective biliary cannulation was adopted. PATIENTS AND METHODS Hands-on training was excluded if patients had ASA grade > 3. The trainee's attempts at selective biliary cannulation were stopped and the procedure taken over by the supervising expert endoscopist if the following factors were encountered: (1) failed cannulation after 5 attempts; (2) unsuccessful cannulation after 10 minutes; (3) edematous papilla; (4) pancreatic duct cannulation ≥ 2 times. After successful ductal cannulation, the trainee was allowed to continue additional hands on training in other aspects such as stone extraction and stenting. RESULTS During the study period, 331 patients underwent ERCP. Trainee group (TG) consisted of 85 patients; mean age 70 (range 27-99). Expert group (EG) consisted of 246 patients; mean age 65 (range 19-98). The overall technical success rate was 97.9% and there was no significant difference between TG (98.8%) and EG (97.6%). The overall complication rate was 3.9% and there was no difference between TG (3.5%) and EG (4%). In TG, although inadvertent pancreatic duct cannulation occurred in 12/85 (14.1%), acute pancreatitis developed only in 3/85 (3.5%). CONCLUSION The high success and low complication rates in trainee-involved and expert-only ERCP procedures were similar. While using a protocol-based strategy, good clinical outcome during the provision of hands-on training for ERCP was observed.

OBJECTIVE: Cough and laryngo-pharyngeal symptoms (LPS) are associated with gastroesophageal reflux disease (GERD). The role of acid reflux (AR) and non-acid reflux (NAR) in atypical GERD pathogenesis is controversial. The aims of the study were to determine the prevalence of high esophageal acid exposure time (AET) in patients presenting with cough or LPS and determine the incremental yield of multichannel intraluminal impedance–pH (MII-pH) monitoring. METHODS: We undertook a prospective study of patients with cough or LPS referred for GERD evaluation between January 2009 and May 2011. All patients underwent esophageal manometry, gastroscopy and MII-pH. Patients' characteristics, gastroscopy findings, distal esophageal AET, bolus exposure (BE) time and numbers of AR and NAR episodes in the proximal and distal esophagus were studied. RESULTS: Overall 50 patients (22 male, mean age 47.5 ± 14.2 years) were evaluated for unexplained chronic cough (n = 23, 46.0%), and LPS symptoms including globus (n = 10, 20.0%), sore throat (n = 12, 24.0%) and hoarse voice (n = 5, 10.0%). A normal gastroscopy, Los Angeles grade A and B esophagitis occurred in 44 (88.0%), 5 (10.0%) and 1 (2.0%) patient, respectively. Seven (14.0%) recorded elevated AET (chronic cough, 4; sore throat, 2; and hoarse voice, 1). Nine patients recorded abnormal impedance characteristics (raised BE time and/or increased reflux numbers) despite a normal AET leading to an incremental diagnostic yield of 18%. CONCLUSION: An isolated high AET is uncommon in patients with cough or LPS. Combined MII-pH improves the diagnostic yield in patients with atypical GERD manifestations.

Magnesium alloys possess unique advantages to be used as biodegradable implants for clinical applications. In this study, in vitro cells responses and degradation behaviors of magnesium alloy M1A in simulated body fluid (SBF) and albumin-containing SBF (A-SBF) were systematically investigated. Cell responses, in terms of Cell morphology and cell proliferation, imply that M1A possesses good viability for MG63 cells. The corrosion behaviors of M1A are strongly affected by the addition of albumin through the combined effects of adsorption and chelation. Electrochemical testing indicates that such an absorbed albumin layer makes M1A to be more noble with a smaller corrosion current. Corrosion rate monitored by hydrogen evolution rate suggests that the quickly adsorbed albumin serves as an effective protective layer, resulting in a much slower hydrogen release rate at initial stage. With increasing immersion time, a higher corrosion rate is observed since the chelation effect exerts more significant acceleration effects on the removal of the passivation layer. The corrosion mode evaluated by surface morphology of the samples changes from a nonuniform-anisotropic mode for M1A in SBF to a uniform-isotropic mode for M1A in A-SBF.

OBJECTIVE: The use of early precut during endoscopic retrograde cholangiopancreatography (ERCP) is controversial because of its association with a higher risk of complications. This study examined the efficacy and safety of a strategy of early precut for biliary access during difficult ERCP in a general hospital. METHODS: Data from January 2007 to June 2009 were reviewed. Criteria for performing early precut were: (i) inadvertent guidewire cannulation of pancreatic duct on three occasions; (ii) biliary stone impacted at papilla; (iii) inability to achieve deep cannulation within 10 min. Study exclusion criteria were: (i) the inability to visualize the papilla because of anatomical distortions; (ii) complete tumour occlusion of distal bile duct; (iii) failure to adhere to inclusion criteria. The efficacy and safety of this strategy of early precut for biliary access was analyzed. RESULTS: A total of 765 ERCP cases were analyzed. A precut was performed in 55 out of 765 cases (7.2%). There were no significant differences in terms of age, gender and diagnoses between the precut and no precut groups. After precut immediate biliary cannulation was achieved in 89% of patients and this increased to 98.2% with a repeat ERCP. The overall complication rate after ERCP was 2.1% (bleeding: 0.7%; pancreatitis: 1.3%; perforation: 0.3%). The only complication after the precut was pancreatitis, and this was not significantly different from the group without a precut (1.8 vs 1.3%). CONCLUSION: The strategy of early precut for biliary access was safe and effective.

Background The roadmap approach is recommended to guide chronic hepatitis B treatment. We evaluated the cost- effectiveness of various treatment strategies in the global market. Methods Lamivudine and telbivudine were tested in roadmap models with switch-to tenofovir if HBV was detectable at week 24 or add-on tenofovir if resistance developed at year 1. Tenofovir and entecavir were tested as continuous monotherapy. In the reference arm, lamivudine was used with add-on tenofovir if resistance developed at year 1. The primary measure of effectiveness was undetectable HBV DNA at year 2. Cost-effectiveness was measured by incremental cost-effectiveness ratio (ICER) in US dollars against the reference arm. Results In the US and Germany, costs of the reference arms were US $14,486 and US $9,998 for hepatitis B e antigen (HBeAg)-positive and US $11,398 and US $7,531 for HBeAg-negative patients, respectively. In HBeAg-positive patients, the lamivudine roadmap was most cost-effective (ICER US $15,260 in the US and US $29,113 in Germany) with comparable effectiveness (75.1%) to other strategies. In HBeAg-negative patients, tenofovir and entecavir monotherapies were most effective (91–96%) and cost- effective (ICER US $31,297–43,387 in the US and US $53,976–59,822 in Germany). In Asia, where telbivudine cost was lower, both telbivudine and lamivudine roadmaps were cost-effective in HBeAg-positive patients. Tenofovir would be most cost-effective in HBeAg-negative patients if its cost equaled that of telbivudine in Asia. Conclusions In HBeAg-positive patients, lamivudine roadmap was most cost-effective; in Asia, telbivudine roadmap had comparable cost-effectiveness to lamivudine roadmap because of the relatively low price of telbivudine. In HBeAg-negative patients, entecavir and tenofovir monotherapies were more cost-effective than the roadmap models.

Introduction: There are limited data on the use of endosonography-guided fine-needle aspiration (EUS-FNA) to determine the nature of left adrenal lesions. We described our experience in performing EUS-FNA of left adrenal lesions. Clinical Picture: During a 20-week period, data on consecutive patients who underwent EUS with or without EUS-FNA were prospectively captured. Patients with a left adrenal mass and who underwent EUS-FNA formed our study population. Treatment: EUS-FNA. Outcome: A total of 119 consecutive patients underwent diagnostic EUS +/- FNA, during which the left adrenal gland was routinely examined. Twelve of these patients underwent EUS as part of lung cancer staging and among these 12 lung cancer patients, 2 had left adrenal masses detected by computed tomography (CT). EUS detected left adrenal nodules in 2 other patients which were not visualised by CT. The overall prevalence of a left adrenal mass was 3.4%; in the subgroup with confirmed lung cancer, the prevalence was 33.3%. All 4 patients were male, with a mean age of 76.3 years (range, 67 to 87). The mean size of the left adrenal lesion was 30.4 mm (range, 9 to 84.8). EUS-FNA of the left adrenal lesions was performed under Doppler guidance. The mean number of needle passes was 2 (range, 1 to 4). A cellular aspirate was obtained in all patients. No procedural complications occurred. Metastatic non-small cell lung cancer was diagnosed in 2 patients, including a lesion missed on CT. For the other 2 cases, EUS-FNA revealed benign adrenal cells. Conclusions: EUS-FNA appears safe and useful for the evaluation of left adrenal masses. Key words: Adrenal gland neoplasms, Endosonography

Cancers are among the leading causes of morbidity and mortality worldwide, with gastrointestinal (GI) luminal cancers accounting for a large proportion of cancer incidence. Chemoprevention of GI luminal cancers is important to reduce this cancer burden. Screening for and eradication of Helicobacter pylori (H. pylori) in areas with high gastric cancer incidence is a safe and effective strategy to decrease the incidence of gastric cancer. Eradication of H. pylori also seems to be effective in preventing metachronous cancer development after endoscopic resection of early gastric cancer. For the average risk individual, COX inhibitors may have a role in reducing the incidence of adenoma formation as well as colorectal cancer, bearing in mind its inherent risks. There is currently insufficient evidence to recommend a chemoprevention agent against esophageal and small intestine cancer.

Clarithromycin-based triple therapy (TT) is the first-line treatment for Helicobacter pylori infection in Singapore. There is awareness that TT may no longer be effective due to increased clarithromycin resistance rates. Sequential therapy (ST) and concomitant therapy (CT) are alternative treatment regimens. This study aimed to compare the efficacy of 10-day TT, ST, and CT as first-line treatment for H. pylori infection.A randomized study conducted in a teaching hospital. Patients aged 21 years and older with newly diagnosed H. pylori infection were randomized to 10-day TT, ST, or CT. Treatment outcome was assessed by 13-carbon urea breath test at least 4 weeks after therapy. Intention to treat (ITT), modified ITT (MITT), and per protocol (PP) analyses of the eradication rates were performed.A total of 462 patients were enrolled (ST: 154; TT 155; CT 153). Patient demographics were similar. Eradication rates for ST versus TT versus CT: ITT analysis: 84.4% versus 83.2% versus 81.7% (P = not significant [NS]); MITT analysis: 90.3% versus 92.1% versus 94.7% (P = NS); PP analysis: 94.1% versus 92.8% versus 95.4% (P = NS). Antibiotic resistance rates for amoxicillin, clarithromycin, and metronidazole were 4.7%, 17.9%, and 48.1%, respectively. Dual clarithromycin and metronidazole resistance occurred in 7.5%. Dual resistance and lack of compliance were predictors of treatment failure.TT, ST, and CT all achieved eradication rates above 80% on ITT and above 90% on MITT and PP analyses. Dual resistance and lack of compliance were predictors of treatment failure (clinicaltrials.gov: NCT02092506).

OBJECTIVE: Endoscopic ultrasound has emerged as the leading modality to assess the T and N stage in gastric cancer. This study aimed to assess the accuracy of TN staging by endoscopic ultrasound in routine clinical practice in Singapore. METHODS: Over a period of 7 years, 77 patients (male: 70%; median age 62.8 years) with gastric cancer underwent preoperative staging with endoscopic ultrasound. Fifty-seven patients eventually underwent surgery with tissues available for histopathological staging and comparison. RESULTS: The tumor locations were: cardia: 13; corpus: 20; incisura: 19; antrum: 25. The majority was poorly differentiated (57.1%); 26% were moderately differentiated and 16.9% were well differentiated adenocarcinoma. Compared to pathological staging, the overall accuracy of T staging by endoscopic ultrasound was 77.2% (17.5% under-staged: 5.3% over-staged). The staging accuracy of T1 (92.9%) and T3 (81.8%) was higher than T2 (57.1%) and T4. For N staging, the accuracy of endoscopic ultrasound was 59.6% (26.3% under-staged; 14% over-staged); this was significantly superior to computer tomography (43.9%). CONCLUSION: Endoscopic ultrasound is useful for the T staging of gastric cancer, with an overall accuracy rate of 77%, and up to 93% for T1 lesions. Under-staging may occur due to microscopic tumor infiltration, while over-staging may arise due to inflammatory reactions. The accuracy of N staging is lower at 60%, but could be further improved with the use of fine needle aspiration.