Search

Introduction: The cost-effectiveness of screening asymptomatic non-alcoholic fatty liver disease (NAFLD) patients remains debatable, with current studies assuming lifelong benefits of NAFLD screening while neglecting cardiovascular outcomes. This study aims to assess the cost-effectiveness of NAFLD screening among type 2 diabetes mellitus (T2DM) patients, and to establish a price threshold for NAFLD treatment, when it becomes available. Method: A Markov model was constructed comparing 4 screening strategies (versus no screening) to identify NAFLD with advanced fibrosis among T2DM patients: fibrosis-4 (FIB-4), vibration-controlled transient elastography (VCTE), FIB-4 and VCTE (simultaneous), and FIB-4 and VCTE (sequential). Sensitivity analyses and price threshold analyses were performed to assess parameter uncertainties in the results. Results: VCTE was the most cost-effective NAFLD screening strategy (USD24,727/quality-adjusted life year [QALY]), followed by FIB-4 (USD36,800/QALY), when compared to no screening. Probabilistic sensitivity analysis revealed a higher degree of certainty for VCTE as a cost-effective strategy compared to FIB-4 (90.7% versus 73.2%). The duration of expected screening benefit is the most influential variable based on incremental cost-effectiveness ratio tornado analysis. The minimum duration of screening benefit for NAFLD screening to be cost-effective was at least 2.6 years. The annual cost of NAFLD treatment should be less than USD751 for NAFLD screening to be cost-effective. Conclusion: Both VCTE and FIB-4 are cost-effective NAFLD screening strategies among T2DM patients in Singapore. However, given the lack of access to VCTE at primacy care and potential budget constraints, FIB-4 can also be considered for NAFLD screening among T2DM patients in Singapore. Keywords: Cost-effectiveness analysis, fatty liver, screening, liver fibrosis, population health

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.

Gastric cancer (GC) has a good prognosis, if detected at an early stage. The intestinal subtype of GC follows a stepwise progression to carcinoma, which is treatable with early detection and intervention using high-quality endoscopy. Premalignant lesions and gastric epithelial polyps are commonly encountered in clinical practice. Surveillance of patients with premalignant gastric lesions may aid in early diagnosis of GC, and thus improve chances of survival. An expert professional workgroup was formed to summarise the current evidence and provide recommendations on the management of patients with gastric premalignant lesions in Singapore. Twenty-five recommendations were made to address screening and surveillance, strategies for detection and management of gastric premalignant lesions, management of gastric epithelial polyps, and pathological reporting of gastric premalignant lesions. Keywords: Early gastric neoplasia, endoscopic surveillance, gastric cancer, intestinal metaplasia, polyp

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We analyzed 1256 gastric samples (1152 IMs) from 692 subjects through a prospective 10-year study. We identified 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9), largely occurring as small clonal events. Analysis of clonal dynamics between and within subjects, and also longitudinally across time, revealed that IM clones are likely transient but increase in size upon progression to dysplasia, with eventual transmission of somatic events to paired GCs. Single-cell and spatial profiling highlighted changes in tissue ecology and lineage heterogeneity in IM, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling revealed expression-based molecular subtypes of IM, including a body-resident “pseudoantralized” subtype associated with incomplete histology, antral/intestinal cell types,ARID1Amutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical- genomic models outperform clinical-only models in predicting IMs likely to progress. Our results raise opportunities for GC precision prevention and interception by highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression.

The primary objectives of this study were to investigate the suitability of a 6-probe cocktail (caffeine, tolbutamide, omeprazole, dextromethorphan, midazolam, and digoxin) to be used as a tool for assessing the activity of drug metabolizing enzymes and transporters, and examine differences in the way drugs are handled among groups with different genetic regulation of these processes. This was a single-center, open-label, phase I clinical study involving 20 young, healthy Chinese volunteers (equal gender distribution). The subjects were administered a single, oral dose of the 6-probe cocktail and serum samples were collected to assess the disposition of the different probe substrates and produced metabolites. The serum samples were analyzed using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry technology. The DNA samples were subjected to whole exome sequencing. Nineteen healthy volunteers completed the study. The 6-probe cocktail was safe and well-tolerated by all the subjects. The parent substrates and metabolites-caffeine (paraxanthine), dextromethorphan (dextrorphan), digoxin, midazolam (1-hydroxy-midazolam), omeprazole (5-hydroxy-omeprazole), and tolbutamide (4-hydroxy-tolbutamide)-were within the detectable window. Genetic variations known to alter drug metabolism (CYP2D6*10, CYP2C19*2, CYP2C19*3, and CYP2C9*3) were identified and generally correlated with phenotypic status. The 6-probe cocktail appeared to be suitable for assessing drug metabolizing activities. This, in conjunction with individual genetics, will pave the way for the implementation of personalized medicine in clinical practice. This will hopefully improve efficacy and reduce the incidence of adverse drug reactions.

Colonoscopy with endoscopic resection of detected colonic adenomas interrupts the adenoma-carcinoma sequence and reduces the incidence of colorectal cancer and cancer-related mortality. In the past decade, there have been significant developments in instruments and techniques for endoscopic polypectomy. Guidelines have been formulated by various professional bodies in Europe, Japan and the United States, but some of the recommendations differ between the various bodies. An expert professional workgroup under the auspices of the Academy of Medicine, Singapore, was set up to provide guidance on the endoscopic management of colonic polyps in Singapore. A total of 23 recommendations addressed the following issues: accurate description and diagnostic evaluation of detected polyps; techniques to reduce the risk of post-polypectomy bleeding and delayed perforation; the role of specific endoscopic resection techniques; the histopathological criteria for defining endoscopic cure; and the role of surveillance colonoscopy following curative resection.

Three subcategories of high-risk flat and depressed lesions (FDLs), laterally spreading tumors non-granular type (LST-NG), depressed lesions, and large sessile serrated lesions (SSLs), are highly attributable to post-colonoscopy colorectal cancer (CRC). Efficient and organized educational programs on detecting high-risk FDLs are lacking. We aimed to explore whether a web-based educational intervention with training on FIND clues (fold deformation, intensive stool/mucus attachment, no vessel visibility, and demarcated reddish area) may improve the ability to detect high-risk FDLs.This was an international web-based randomized control trial that enrolled non-expert endoscopists in 13 Asian countries. The participants were randomized into either education or non-education group. All participants took the pre-test and post-test to read 60 endoscopic images (40 high-risk FDLs, five polypoid, 15 no lesions) and answered whether there was a lesion. Only the education group received a self-education program (video and training questions and answers) between the tests. The primary outcome was a detection rate of high-risk FDLs.In total, 284 participants were randomized. After excluding non-responders, the final data analyses were based on 139 participants in the education group and 130 in the non-education group. The detection rate of high-risk FDLs in the education group significantly improved by 14.7% (66.6-81.3%) compared with -0.8% (70.8-70.0%) in the non-education group. Similarly, the detection rate of LST-NG, depressed lesions, and large SSLs significantly increased only in the education group by 12.7%, 12.0%, and 21.6%, respectively.Short self-education focusing on detecting high-risk FDLs was effective for Asian non-expert endoscopists. (UMIN000042348).

A combination of platelet and elastography (PE criteria) was proposed to identify compensated advanced chronic liver disease (cACLD) patients at risk of liver decompensation. We aim to validate and refine PE criteria by developing a new predictive score to predict decompensation in Asian cACLD patients.An international cohort of 633 cACLD patients with liver stiffness measurement (LSM) and esophagogastroduodenoscopy performed were included. We validated PE criteria to predict first liver decompensation using competing risk analysis, with death and hepatocellular carcinoma as competing events. We developed a predictive model using proportional subdistribution hazard regression. Prognostic accuracy was compared with the model of end-stage liver disease (MELD), albumin-bilirubin (ALBI), and ALBI-FIB-4 score using time-dependent area under operative characteristic curve (tAUC).Sixty patients developed decompensation over the median follow-up of 39 months. Favorable Baveno VI status ruled out cACLD patients at risk of liver decompensation. LSM 25 kPa was suboptimal to predict cACLD patients who will develop liver decompensation. We developed CHESS-ALARM score by incorporating age, platelet, and gender into LSM. CHESS-ALARM score (tAUC = 0.86, 95% confidence interval [CI]: 0.79-0.94) has significantly higher accuracy than MELD (tAUC: 0.61), ALBI (tAUC: 0.62), ALBI-FIB-4 (tAUC: 0.70), and LSM 25 kPa (tAUC: 0.54) to predict liver decompensation at 5 years (P 0.05 for all). Patients with CHESS-ALARM score ≥ -0.37 had an 11-fold higher risk of decompensation (subdistribution hazard ratio = 11.2, 95% CI: 5.1-24.5).CHESS-ALARM score can be readily incorporated into clinical practice of cACLD patients to estimate individual risk of liver decompensation; however, more data are required in morbidly obese cACLD patients of nonviral etiology.

The effectiveness of the hemostatic powder TC-325 as a single endoscopic treatment for acute nonvariceal upper gastrointestinal bleeding is uncertain.To compare TC-325 with standard endoscopic hemostatic treatments in the control of active bleeding from nonvariceal upper gastrointestinal causes.One-sided, noninferiority, randomized, controlled trial. (ClinicalTrials.gov: NCT02534571).University teaching hospitals in the Asia-Pacific region.224 adult patients with acute bleeding from a nonvariceal cause on upper gastrointestinal endoscopy.TC-325 (The primary outcome was control of bleeding within 30 days. Other outcomes included failure to control bleeding during index endoscopy, recurrent bleeding after initial hemostasis, further interventions, blood transfusion, hospitalization, and death.224 patients were enrolled (136 with gastroduodenal ulcers [60.7%], 33 with tumors [14.7%], and 55 with other causes of bleeding [24.6%]). Bleeding was controlled within 30 days in 100 of 111 patients (90.1%) in the TC-325 group and 92 of 113 (81.4%) in the standard treatment group (risk difference, 8.7 percentage points [1-sided 95% CI, 0.95 percentage point]). There were fewer failures of hemostasis during index endoscopy with TC-325 (3 [2.7%] vs. 11 [9.7%]; odds ratio, 0.26 [CI, 0.07 to 0.95]). Recurrent bleeding within 30 days did not differ between groups (9 [8.1%] vs. 10 [8.8%]). The need for further interventions also did not differ between groups (further endoscopic treatment: 8 [7.2%] vs. 10 [8.8%]; angiography: 2 [1.8%] vs. 4 [3.5%]; surgery: 1 [0.9%] vs. 0). There were 14 deaths in each group (12.6% vs. 12.4%).Clinicians were not blinded to treatment.TC-325 is not inferior to standard treatment in the endoscopic control of bleeding from nonvariceal upper gastrointestinal causes.General Research Fund to the University Grants Committee, Hong Kong SAR Government.

Introduction: In Singapore, non-anaesthesiologists generally administer sedation during gastrointestinal endoscopy. The drugs used for sedation in hospital endoscopy centres now include propofol in addition to benzodiazepines and opiates. The requirements for peri-procedural monitoring and discharge protocols have also evolved. There is a need to develop an evidence-based clinical guideline on the safe and effective use of sedation by non-anaesthesiologists during gastrointestinal endoscopy in the hospital setting. Methods: The Academy of Medicine, Singapore appointed an expert workgroup comprising 18 gastroenterologists, general surgeons and anaesthesiologists to develop guidelines on the use of sedation during gastrointestinal endoscopy. The workgroup formulated clinical questions related to different aspects of endoscopic sedation, conducted a relevant literature search, adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology and developed recommendations by consensus using a modified Delphi process. Results: The workgroup made 16 recommendations encompassing 7 areas: (1) purpose of sedation, benefits and disadvantages of sedation during gastrointestinal endoscopy; (2) pre-procedural assessment, preparation and consent taking for sedation; (3) Efficacy and safety of drugs used in sedation; (4) the role of anaesthesiologist-administered sedation during gastrointestinal endoscopy; (5) performance of sedation; (6) post-sedation care and discharge after sedation; and (7) training in sedation for gastrointestinal endoscopy for non-anaesthesiologists. Conclusion: These recommendations serve to guide clinical practice during sedation for gastrointestinal endoscopy by non-anaesthesiologists in the hospital setting. Keywords: Benzodiazepines, gastrointestinal endoscopy opiates, propofol, sedation

Introduction: The COVID-19 outbreak abruptly restricted gastrointestinal (GI) endoscopy services during the first wave of the pandemic. We aimed to assess the impact of COVID-19 on the practice of GI endoscopy in Asian countries. Methods: This was an International Questionnaire-based Internet Survey conducted at multiple facilities by the International Gastrointestinal Consensus Symposium. A total of 166 respondents in Japan, China, Hong Kong, South Korea, Philippines, Thailand, Indonesia, and Singapore participated in this study. Results: The volume of endoscopic screening or follow-up endoscopies and therapeutic endoscopies were markedly reduced during the first wave of the pandemic, which was mainly attributed to the decreased number of outpatients, cancellations by patients, and adherence to the guidelines of academic societies. The most common indications for GI endoscopy during the first wave were GI bleeding, cholangitis or obstructive jaundice, and a highly suspicious case of neoplasia. The most common GI symptoms of COVID-19 patients during the infected period included diarrhea, nausea, and vomiting. The pandemic exacerbated some GI diseases, such as functional dyspepsia and irritable bowel syndrome. There were cases with delayed diagnosis of cancers due to postponed endoscopic procedures, and the prescription of proton pump inhibitors/potassium-competitive acid blockers, steroids, immunosuppressive agents, and biologics was delayed or canceled. The personal protective equipment used during endoscopic procedures for high-risk patients were disposable gloves, disposable gowns, N95 or equivalent masks, and face shields. However, the devices on the patient side during endoscopic procedures included modified surgical masks, mouthpieces with filters, and disposable vinyl boxes or aerosol boxes covering the head. Furthermore, the time for education, basic research, clinical research, and daily clinical practice decreased during the first wave. Conclusion: This study demonstrated that the COVID-19 pandemic profoundly affected the method of performing GI endoscopy and medical treatment for patients with GI diseases in Asian countries.

Background and aims Artificial intelligence has been extensively studied to assist clinicians in polyp detection, but such systems usually require expansive processing power, making them prohibitively expensive and hindering wide adaption. The current study used a fast object detection algorithm, known as the YOLOv3 algorithm, to achieve real-time polyp detection on a laptop. In addition, we evaluated and classified the causes of false detections to further improve accuracy. Methods The YOLOv3 algorithm was trained and validated with 6,038 and 2,571 polyp images, respectively. Videos from live colonoscopies in a tertiary centre and those obtained from public databases were used for the training and validation sets. The algorithm was tested on 10 unseen videos from the CVC-Video ClinicDB dataset. Only bounding boxes with an intersection over union area of > 0.3 were considered positive predictions. Results Polyp detection rate in our study was 100%, with the algorithm able to detect every polyp in each video. Sensitivity, specificity and F1 score were 74.1%, 85.1% and 83.3, respectively. The algorithm achieved a speed of 61.2 frames per second (fps) on a desktop RTX2070 GPU and 27.2 fps on a laptop GTX2060 GPU. Nearly a quarter of false negatives happened when the polyps were at the corner of an image. Image blurriness accounted for approximately 3% and 9% of false positive and false negative detections, respectively. Conclusion The YOLOv3 algorithm can achieve real-time poly detection with high accuracy and speed on a desktop GPU, making it low-cost and accessible to most endoscopy centres worldwide.

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

Gastric cancer (GC) has a good prognosis, if detected at an early stage. The intestinal subtype of GC follows a stepwise progression to carcinoma, which is treatable with early detection and intervention using high-quality endoscopy. Premalignant lesions and gastric epithelial polyps are commonly encountered in clinical practice. Surveillance of patients with premalignant gastric lesions may aid in early diagnosis of GC, and thus improve chances of survival. An expert professional workgroup was formed to summarise the current evidence and provide recommendations on the management of patients with gastric premalignant lesions in Singapore. Twenty-five recommendations were made to address screening and surveillance, strategies for detection and management of gastric premalignant lesions, management of gastric epithelial polyps, and pathological reporting of gastric premalignant lesions.

Effects of linked-color imaging (LCI) on colorectal lesion detection and colonoscopy quality remain controversial. This study compared the detection rates of adenoma and other precursor lesions using LCI vs white-light imaging (WLI) during screening, diagnostic, and surveillance colonoscopies.This randomized controlled trial was performed at 11 institutions in 4 Asian countries/regions. Patients with abdominal symptoms, a primary screening colonoscopy, positive fecal immunochemical test results, or undergoing postpolypectomy surveillance were recruited and randomly assigned in a 1:1 ratio to either the LCI or high-definition WLI group. The primary outcome was adenoma detection rate (ADR). Secondary outcomes were polyp detection rate, advanced ADR, sessile serrated lesion (SSL) detection rate, and the mean number of adenomas per colonoscopy. The recommended surveillance schedule distribution after trial colonoscopy was analyzed.Between November 2020 and January 2022, there were 3050 participants (LCI, n = 1527; WLI, n = 1523) recruited. The LCI group ADR was significantly higher than the WLI group ADR using intention-to-treat (58.7% vs 46.7%; P.01) and per-protocol analyses (59.6% vs 46.4%; P.01). The LCI group polyp detection rates (68.6% vs 59.5%; P.01), SSL detection rates (4.8% vs 2.8%; P.01), and adenomas per colonoscopy (1.48 vs 1.02; P.01) also were significantly higher. However, the LCI group advanced ADR was nonsignificantly higher (13.2% vs 11.0%; P = .06). The LCI group was categorized in significantly shorter recommended surveillance schedules than the WLI group (P.01).Compared with WLI, LCI improved adenoma and other polyp detection rates, including SSLs, resulting in alteration of the recommended surveillance schedule after screening, diagnostic, and postpolypectomy surveillance colonoscopies.UMIN000042432 (https://www.umin.ac.jp/ctr/index.htm).

BACKGROUNDPatients undergoing immune-modifying therapies demonstrate a reduced humoral response after COVID-19 vaccination, but we lack a proper evaluation of the effect of such therapies on vaccine-induced T cell responses.METHODSWe longitudinally characterized humoral and spike-specific T cell responses in patients with inflammatory bowel disease (IBD), who were on antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors, and/or other biologic treatment (anti-integrin or anti-p40) for up to 6 months after completing 2-dose COVID-19 mRNA vaccination.RESULTSWe demonstrate that a spike-specific T cell response was not only induced in treated patients with IBD at levels similar to those of healthy individuals, but also sustained at higher magnitude for up to 6 months after vaccination, particularly in those treated with TNF inhibitor therapy. Furthermore, the spike-specific T cell response in these patients was mainly preserved against mutations present in SARS-CoV-2 B.1.1.529 (Omicron) and characterized by a Th1/IL-10 cytokine profile.CONCLUSIONDespite the humoral response defects, patients under immune-modifying therapies demonstrated a favorable profile of vaccine-induced T cell responses that might still provide a layer of COVID-19 protection.FUNDINGThis study was funded by the National Centre for Infectious Diseases (NCID) Catalyst Grant (FY2021ES) and the National Research Fund Competitive Research Programme (NRF-CRP25-2020-0003).

Decompensated cirrhosis is characterized by chronic inflammation and severe portal hypertension leading to systemic circulatory dysfunction. Albumin infusion has been widely used in decompensated cirrhosis in patients with spontaneous bacterial peritonitis, large-volume paracentesis and hepatorenal syndrome. Emerging data suggest long-term albumin infusion has both oncotic and non-oncotic properties which may improve the clinical outcomes in decompensated cirrhosis patients. We review the current literature on both the established and potential role of albumin, and specifically address the controversies of long-term albumin infusion in decompensated cirrhosis patients.

BACKGROUND AND AIM Gastrointestinal (GI) lesions may have subtle morphological changes. Linked color imaging (LCI) combines narrow-band wavelength light and white light imaging (WLI) in appropriate balance to enhance lesion detection. We compared the detection rates of upper GI lesions using LCI and WLI. METHOD Patients were randomized in a 1:1 ratio to receive tandem gastroscopy with WLI inspection followed by LCI, or vice versa. Endoscopic examination was performed using the EG-L590ZW gastroscope and the LASEREO endoscope system (Fujifilm Co., Tokyo, Japan). Histology was reported by a specialist GI pathologist blinded to the technique of lesion detection and was used as the gold standard for diagnosis. RESULTS Ninety patients (mean age 66.8 years, 51.5% male patients) were randomized to either LCI examination first followed by WLI (LCI-WLI), or vice versa (WLI-LCI). An 18.9% of gastroscopies in the study were for surveillance of previously known gastric cancer precursors. Ten patients (11.1%) had a history of Helicobacter pylori infection. There was no significant difference in the time taken for examination under LCI (311 ± 96 s) and WLI (342 ± 86 s) (P = 0.700). LCI detection rates were higher than WLI detection rates for gastric cancer precursors such as atrophic gastritis (2.19% vs 0.55%) (P

The management of Helicobacter pylori infection in Singapore remains a clinical challenge. Similar to other regions, there has been an increase in antibiotic resistance rates through the years. Nonetheless, over the past two decades, clarithromycin-based triple therapy has continued to be used as the first line treatment option, with an eradication rate exceeding 90%, although the accepted treatment duration must now be lengthened from 1 to 2 weeks to maintain efficacy. Concomitant and sequential therapies did not demonstrate superiority over standard triple therapy. Current empiric second line treatment utilizes either bismuth-based quadruple therapy or levofloxacin-based triple therapy, but outcomes remain less than ideal. Identifying options to further improve treatment success rates is challenging. Strategies being considered include the use of potent acid suppressants, such as vonoprazan, and H. pylori culture and antibiotic susceptibility testing-guided therapy. (Gut Liver 2021;15:13-18)

In this paper, we aim to provide professional guidance to clinicians who are managing patients with chronic liver disease during the current coronavirus disease 2019 (COVID-19) pandemic in Singapore. We reviewed and summarised the available relevant published data on liver disease in COVID-19 and the advisory statements that were issued by major professional bodies, such as the American Association for the Study of Liver Diseases and European Association for the Study of the Liver, contextualising the recommendations to our local situation.

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.

Patients undergoing immune-modifying therapies demonstrate a reduced humoral response after COVID-19 vaccination, but we lack a proper evaluation of the impact of such therapies on vaccine-induced T cell responses. Here, we longitudinally characterised humoral and Spike-specific T cell responses in inflammatory bowel disease (IBD) patients who are on antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors and/or other biologic treatment (anti-integrin or anti-p40) after mRNA vaccination up to 3 months after completing two vaccine doses. We demonstrated that a Spike-specific T cell response is not only induced in treated IBD patients at levels similar to healthy individuals, but also sustained at higher magnitude, particularly in those treated with TNF inhibitor therapy. Furthermore, the Spike-specific T cell response in these patients is mainly preserved against mutations present in SARS-CoV-2 B.1.1.529 (Omicron) and characterized by a Th1/IL-10 cytokine profile. Thus, despite the humoral response defects, the favourable profile of vaccine-induced T cell responses might still provide a layer of COVID-19 protection to patients under immune-modifying therapies.

Background The use of macroscopic on-site evaluation (MOSE) to estimate the adequacy of a specimen for histological diagnosis during endoscopic ultrasound (EUS)-guided fine-needle tissue acquisition (FNTA) has recently been advocated. This study aimed to evaluate the diagnostic yield of MOSE compared with conventional EUS-FNTA without rapid on-site evaluation (ROSE).Methods This was an international, multicenter, prospective, randomized controlled study. After providing informed consent, consecutive adult patients referred for EUS-FNTA for solid lesions larger than 2 cm were randomized to a MOSE arm or to a conventional arm without ROSE. A designated cytopathologist from each center performed all cytopathological examinations for that center and was blinded to the randomization results. The primary outcome measure was the diagnostic yield, and the secondary outcomes included sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and the rate of procedure-related complications.Results 244 patients (122 conventional, 122 MOSE) were enrolled during the study period. No significant differences between the two arms were found in procedure time or rate of procedure-related adverse events. The diagnostic yield for the MOSE technique (92.6 %) was similar to that for the conventional technique (89.3 %; P = 0.37), with significantly fewer passes made (median: conventional 3, MOSE 2; P Conclusions EUS-FNTA with the MOSE technique provided a similar diagnostic yield to conventional EUS-FNTA technique in the absence of ROSE but with fewer passes. This technique can be used when ROSE is not available.

The landscape of ulcerative colitis has changed in the last two decades. Advancements in pharmacotherapeutics have heralded the introduction of new treatment options, with many agents in development. Better clinical outcomes are seen with tighter disease control, made possible with greater understanding of inflammatory pathways and their blockade with drugs. There has been a resultant shift in treatment targets, beyond symptoms to endoscopic and histological healing. Controlling the burden of disease activity also lowers the risk of developing colorectal cancer. Colorectal cancer screening now requires the use of dye-based agents and high definition colonoscopy to improve detection of colonic neoplasms.

Introduction: Acute malignant large bowel obstruction (MBO) occurs in 8-15% of colorectal cancer patients. Self-expandable metal stents (SEMS) have progressed from a palliative modality to use as bridge-to-surgery (BTS). We aimed to conduct a clinical audit on safety and efficacy of SEMS for MBO in our institution. Methods: Data from a prospectively maintained electronic database in a tertiary referral centre in Singapore was reviewed for all consecutive patients undergoing SEMS insertion for MBO. Technical success defined as successful SEMS deployment across tumour without complications. Clinical success defined as colonic decompression without requiring further surgical intervention. Rates of complications, median time to surgery, types of surgery and rates of recurrence were studied. Results: 79 patients underwent emergent SEMS placement from September 2013 to February 2020. Mean age 68.8±13.8 years, male 43/79 (54%). Mean tumour length 4.2cm±2.2cm; 89.9% (71/79) distal to splenic flexure. Technical and clinical success was 94.9% (75/79) and 98.7% (74/75), respectively. Perforation occurred in 5.1% (4/79), with no cases of stent migration or bleeding. 50/79(63.3%) of SEMS inserted as BTS. Median time to surgery was 20 days (range 6-57). Majority (41/50;82%) underwent minimally invasive surgery (robotic-assisted 7/50,14%; laparoscopic 34/50,68%). Primary anastomosis rate was 98% (49/50). 39 patients had follow-up beyond 1-year post-treatment (median 34 months). Local recurrence and distant metastasis were observed in 4/39(10.3%) and 5/39(12.8%), respectively. Conclusion: SEMS acute MBO has high technical and clinical success rates with a good safety profile. Majority of patients in our audit underwent minimally invasive surgery and primary anastomosis after successful BTS.

H. pylori eradication reduces the risk of gastric malignancies and peptic ulcer disease. First-line therapies include 14-day PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) and PBMT (PPI, bismuth, metronidazole, tetracycline). Second-line therapies include 14-day PBMT and PAL (PPI, amoxicillin, levofloxacin). This clinical audit examined current treatment outcomes in Singapore.Clinical data of H. pylori-positive patientswho underwent empirical first- and second-line eradication therapies from 1 January 2017 to 31 December 2018 were reviewed. Treatment success was determined byA total of 963 patients (862 PAC, 36 PMC [PPI, metronidazole, clarithromycin], 18 PBMT, 13 PBAC [PAC with bismuth], 34 others) and 98 patients (62 PMBT, 15 PAL, 21 others) received first-and second-line therapies respectively. A 14-day treatment duration was appropriately prescribed for first- and second-line therapies in 65.2% and 82.7% of patients, respectively. First-line treatment success rates were noted for PAC (seven-day: 76.9%, ten-day: 88.3%, 14-day: 92.0%), PMC (seven-day: 0, ten-day: 75.0%, 14-day: 69.8%), PBMT (ten-day: 100%, 14-day: 87.5%) and PBAC (14-day: 100%). 14-day treatment was superior to seven-day treatment (90.8% vs. 71.4%; P = 0.028). PAC was superior to PMC (P0.001) but similar to PBMT (P = 0.518) and PBAC (P = 0.288) in 14-day therapies. 14-day second-line PAL and PBMT had similar efficacy (90.9% vs. 82.4%; P = 0.674).First-line empirical treatment using PAC, PBMT and PBAC for 14 days had similar efficacy. Success rates for second-line PBMT and PAL were similar.

BACKGROUND AND AIM Our aim was to evaluate the efficacy and safety of a lumen-apposing metal stent with an electrocautery-enhanced delivery system (EDS-LAMS) for endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) in regular clinical practice. METHODS A retrospective and subsequent prospective analysis was undertaken of all patients who underwent EUS-guided drainage of their PFCs using the EDS-LAMS at 17 tertiary therapeutic endoscopy centers. RESULTS Two hundred eight cases of EDS-LAMS deployment were attempted in 202 patients (mean age 52.9 years) at time of evaluation. Ninety-seven patients had pancreatic pseudocysts (PPs), 75 walled-off pancreatic necrosis (WOPN), 10 acute peripancreatic fluid collections (APFCs), 6 acute necrotic collections (ANCs), and 14 postoperative collections (POCs). Procedural technical success was achieved in 202/208 cases (97.1%). Maldeployment occurred in 7/208 cases (3.4%). Clinical success was achieved in 142/160 (88.8%) patients (PP 90%, WOPN 85.2%, APFC 100%, ANC 75%, POC 100%). Delayed adverse events included stent migration in 15/202 (7.4%), stent occlusion and infection in 16/202 (7.9%), major bleeding in 4/202 (2%), and buried EDS-LAMS in 2/202 (1%). PFC recurrence occurred in 13/142 (9.2%) patients; 9/202 (4.5%) required surgical or radiological intervention for PFC management after EDS-LAMS insertion. CONCLUSIONS This large international multicenter study evaluating the EDS-LAMS for drainage of PFCs in routine clinical practice suggests that the EDS-LAMS are safe and effective for drainage of all types of PFCs; however, further endoscopic therapy is often required for WOPN. Major bleeding was a rare complication in our cohort.

ObjectiveTo investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC.MethodsA prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN).ResultsThere were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; pH. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II–IV.ConclusionsWe suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III–IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.