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BACKGROUND Endoscopic submucosal dissection (ESD) has shown to be effective in management of colorectal neoplasm in the Asian countries, while its implementation in Western countries where endoscopic mucosal resection (EMR) is preferred is still debatable. AIM To compare the surgical, histological, and oncological outcomes between ESD and EMR in the treatment of colorectal polyps, with subgroup analysis comparing the efficacy of ESD and EMR between Japan and the rest of the world. METHODS Embase and Medline databases were searched from inception to October 2020 in accordance with PRISMA guidelines for studies comparing en bloc, complete resection, margin involvement, resection time, need for additional surgery, complications, and recurrence rate of ESD with EMR. RESULTS Of 281344 colorectal polyps from 21 studies were included. When compared to EMR, the pooled analysis revealed ESD was associated with higher en bloc and complete resection rate, and lower lateral margin involvement and recurrence. ESD led to increased procedural time, need for additional surgery, and perforation risk. No significant difference in bleeding risk was found between the two groups. Meta-regression analysis suggested only right colonic polyps correlated with an increased perforation risk in ESD. Confounders including polyp size and invasion depth did not significantly influence the en bloc and complete resection rate, bleeding risk and recurrence. In subgroup analysis, Japan performed better than the rest of the world in both ESD and EMR with perforation risk of 4% and 0.0002%, respectively, as compared to perforation risk of 8% and 1%, respectively, in reports coming from rest of the world. CONCLUSION ESD resulted in better resection outcomes and lower recurrence compared to EMR. With appropriate training, ESD is preferred over EMR as the first-line therapy for resection of colorectal polyps, without restricting to lesions greater than 20 mm and those with high suspicion of submucosal invasion.

Omeprazole is commonly co-prescribed with clopidogrel. Clopidogrel requires bio-activation by cytochrome P450 CYP2C19. Omeprazole may reduce clopidogrel’s antithrombotic efficacy by inhibiting CYP2C19. Studies in Caucasians receiving omeprazole with clopidogrel showed no significant increase in death and myocardial infarction with this drug–drug interaction. There are limited large-scale studies in Asians, who may have a greater prevalence of CYP2C19 loss-of-function polymorphisms. A single centre retrospective cohort study was undertaken based on a review of medication records and prescription data. Patients prescribed clopidogrel from 2009 to 2012 were followed-up with until December 2012 (median:29 months). The primary outcome was all-cause mortality and secondary outcomes were myocardial infarction (MI), cerebrovascular accidents, and subsequent coronary interventions. Of 12,440 patients prescribed clopidogrel, 62%(n = 7714) were on omeprazole (63.8% Chinese, 13.9% Malay, 12.4% Indian, 10.0% others), and 38%(n = 4726) were not on omeprazole or other proton pump inhibitors (62.6% Chinese, 13.5% Malay, 10.7% Indian, 13.2% others). Mortality after co-prescription occurred in 14.3%(n = 1101) of patients, compared to 6.3%(n = 300) of patients prescribed clopidogrel only. Multivariate analysis using propensity score adjusted analysis showed no significant increase in all-cause mortality with co-prescription (adjusted hazards ratio [AHR] 1.13, [95%CI 0.95–1.35]). Patients on co-prescription had a higher risk of subsequent MI (16% vs 3.8%; AHR 2.03 [95%CI 1.70–2.44]), but not of cerebrovascular accidents (5.0% vs 2.0%; AHR 0.98 [95%CI 0.76–1.27]) or coronary interventions (1.7% vs 0.7%; AHR 1.28 [95%CI 0.83–1.96]). The risk of a subsequent MI was higher in the Malay (AHR 2.43 [95%CI 1.68–3.52]) and Chinese (AHR 2.06 [95%CI 1.63–2.60]) population as compared to the Indian (AHR 1.56 [95%CI 1.06–2.31]) population. In conclusion, the use of clopidogrel with omeprazole is associated with an increased risk of MI, but not mortality or stroke, in this multi-ethnic Asian population. These risks appear to vary among different ethnic groups.

White-light endoscopy with biopsy is the current gold standard modality for detecting and diagnosing upper gastrointestinal (GI) pathology. However, missed lesions remain a challenge. To overcome interobserver variability and learning curve issues, artificial intelligence (AI) has recently been introduced to assist endoscopists in the detection and diagnosis of upper GI neoplasia. In contrast to AI in colonoscopy, current AI studies for upper GI endoscopy are smaller pilot studies. Researchers currently lack large volume, well-annotated, high-quality datasets in gastric cancer, dysplasia in Barrett's esophagus and early esophageal squamous cell cancer. This review will look at the latest studies of AI in upper GI endoscopy, discuss some of the challenges facing researchers, and predict what the future may hold in this rapidly changing field.

The endoscope was traditionally used as a diagnostic instrument. In past decades, it has increasingly been adapted for therapeutic intents. Subsequently, the master–slave robotic concept was introduced into the field of endoscopy to potentially reduce the difficulty and complication rates of endoscopic therapeutic procedures. As interest in robotic endoscopy intensified, progressively more robotic endoscopic platforms were developed, tested, and introduced. Nevertheless, the future of robotic endoscopy hinges on the ability to meet specific clinical needs of procedurists. Three aspects are vital in ensuring continued success and clinical adoption of the robotic endoscope—demonstration of clinical safety and cost‐efficacy of the device, widespread availability of directed training opportunities to enhance technical skills and clinical decision‐making capabilities of the procedurist, and continued identification of new clinical applications beyond the current uses of the device. This review provides a brief discussion of the historical development of robotic endoscopy, current robotic endoscopic platforms, use of robotic endoscopy in conventional therapeutic endoscopic procedures, and the future of robotic endoscopy., A successful robotic endoscope must provide beyond the basic requirement of a high functioning endoscopic resection tool. It must be demonstrated to be safe, and cost‐effective for its intended clinical application. Training can be best achieved through the synergy of artificial‐intelligence‐guided deep learning systems and virtual reality. Natural Orifice Transluminal Endoscopic Surgery (NOTES) is an ideal choice for the application of the robotic endoscope as the triangulation afforded by the device effectively solves the challenges faced when performing NOTES using existing endoscopic equipment.

Standard polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection (ESD) are established techniques for the treatment of gastrointestinal tumors. However, resection of submucosal tumors via ESD often results in low rates of microscopically margin-negative (R0) resection and high rates of perforation. Endoscopic full thickness resection (EFTR) overcomes this adverse event and aids in the therapeutic management of complex tumors. Multiple techniques for EFTR have been developed, each with its own advantages and disadvantages. Submucosal tunneling and non-exposed techniques are generally preferable, because the layer of overlying intact mucosa reduces the incidence of intraperitoneal contamination by the gastric fluid and dissemination of the tumor cells. However, adoption of EFTR by endoscopists in clinical practice remains low. The major challenge seems to be the technical difficulty in performing laparoscopic and/or endoscopic suturing using the currently available instruments. We developed a novel robotic endoscopic platform with suturing capabilities to overcome the technical challenges of suturing. This platform allows easy maneuvering and triangulation of the instruments, thus facilitating endoscopic suturing using robotic arms. Our studies have demonstrated that this robotic endoscopic platform with suturing capabilities is an effective and safe method for performing EFTR with endoscopic suturing.

Barrett's esophagus (BE) is a premalignant condition associated with the development of esophageal adenocarcinoma (EAC). Over the past decade, BE and its associated neoplasia has increased in prevalence globally. Current surveillance guidelines aimed to detect and treat BE‐associated dysplasia early in the hope of improving the morbidity and mortality of the condition. However, due to the lack of long‐term data and the proven benefit that surveillance actually improves mortality from EAC, the guidelines of the United States and Europe are slightly different. This review will focus on discussing the surveillance strategy for BE appropriate for the Asian region, taking into account the unique epidemiologic features of this disease in the Asian region., Current surveillance guidelines aim to detect Barrett's esophagus‐associated dysplasia early. However, due to the lack of long‐term data, and proven benefit that surveillance actually improves mortality from esophageal adenocarcinoma, the guidelines coming from the US and Europe are slightly different. This review will discuss the surveillance strategy for Barrett's esophagus appropriate to the Asian region, taking into account the unique epidemiologic features of this disease in the Asian region.

BACKGROUND Gamma-glutamyl transferase (GGT) is associated with the risk of cardiovascular disease (CVD) in the general population. AIM To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). METHODS This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia (referred to as "GO ASIA") workgroup. All patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation (QRISK2-2017; developed by researchers at the United Kingdom National Health Service; https://qrisk.org/2017/; 10-year cardiovascular risk estimation) were included and compared to healthy controls with the same age, sex, and ethnicity. Relative risk was reported. QRISK2 score > 10% was defined as the high-CVD-risk group. Fibrosis stages 3 and 4 (F3 and F4) were considered advanced fibrosis. RESULTS A total of 1122 patients (73%) had complete data and were included in the final analysis; 314 (28%) had advanced fibrosis. The median age (interquartile range [IQR]) of the study population was 53 (44-60) years, 532 (47.4%) were females, and 492 (43.9%) were of Chinese ethnicity. The median 10-year CVD risk (IQR) was 5.9% (2.6-10.9), and the median relative risk of CVD over 10 years (IQR) was 1.65 (1.13-2.2) compared to healthy individuals with the same age, sex, and ethnicity. The high-CVD-risk group was significantly older than the low-risk group (median [IQR]: 63 [59-67] vs 49 [41-55] years; P < 0.001). Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk (P < 0.001). Median GGT level was not different between the two groups (GGT [U/L]: Median [IQR], high risk 60 [37-113] vs low risk 66 [38-103], P = 0.56). There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score (r = 0.02). CONCLUSION The CVD risk of NAFLD patients is higher than that of healthy individuals. Baseline GGT level cannot predict CVD risk in NAFLD patients. However, advanced fibrosis is a predictor of a high CVD risk.

Therapeutic endoscopic resection has gained favor for its ability to achieve high en bloc and histologically complete resection rates via a minimally invasive approach. The main technical difficulties faced by interventionists are first the lack of traction causing suboptimal visualization of the dis section field and second, the lack of triangulation using existing therapeutic apparatuses. These challenges can be overcome with the use of robots and the multiple degrees of freedom afforded by the robotic wrists. Nevertheless, com plications such as bleeding and perforation can occur. It is hence beneficial for the robotic device to be equipped with additional abilities such as suturing. Once the robotic proto types have been fully optimized and marketed, a structured program should be instituted to ensure proper and adequate training of the end-users. The future of robotics should then explore the possibility of developing a soft robot or a robot with more natural human-like movements. A robot with a force feedback mechanism would be superior and improve safety. Eventually, a supervised autonomous robot may per form interventions with greater precision and accuracy than an expert procedurist. This review describes the benefits of robot-assisted endoscopic resections, recent developments aimed at managing iatrogenic complications and future di rections for robotic endoscopy. (Gut Liver 2020;14:150-152)

Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD) are the standard of care in malignant biliary obstruction cases. Recently, endoscopic ultrasound-guided biliary drainage (EUS-BD) has been widely used after unsuccessful ERCP. However, the patient’s clinical impact of EUS-BD over PTBD is still not obvious. Therefore, this case series study aims to evaluate the clinical outcomes of patients with advanced malignant biliary obstruction who underwent EUS-BD after failed ERCP. A retrospective database study was performed between January 2016 and June 2018 in patients with advanced malignant biliary obstruction. Patients were consecutively enrolled without randomization. Treatment options consisted of ERCP and PTBD or EUS-BD if ERCP failed. Based on 144 biliary obstruction cases, 38 patients were enrolled; 24 (63.2%) were men. The patients’ mean age was 66.8 ± 12.36 years. The most common cause of malignant biliary obstruction was pancreatic cancer (44.7%). Biliary drainage was achieved by ERCP (39.5%), PTBD (39.5%), and EUS-BD (21.1%). The technical success rate was 86.7% by PTBD and 87.5% by EUS-BD (p = 1.000), while the clinical success rate was 93.3% by PTBD and 62.5% by EUS-BD (p = 0.500). The median survival in patients who underwent PTBD versus those wo underwent EUS-BD was 11 versus 3 months (log-rank p = 0.455). In conclusion, there is no significant advantage of EUS-BD when compared to PTBD in terms of clinical success and survival benefit in advanced malignant biliary obstruction.

Barrett's esophagus (BE), a premalignant condition of the lower esophagus, is increasingly prevalent in Asia. However, endoscopic and histopathological criteria vary widely between studies across Asia, making it challenging to assess comparability between geographical regions. Furthermore, guidelines from various societies worldwide provide differing viewpoints and definitions, leading to diagnostic challenges that affect prognostication of the condition. In this review, the authors discuss the controversies surrounding the diagnosis of BE, particularly in Asia. Differences between guidelines worldwide are summarized with further discussion regarding various classifications of BE used, different definitions of gastroesophageal junction used across geographical regions and the clinical implications of intestinal metaplasia in the setting of BE. Although many guidelines recommend the Seattle protocol as the preferred approach regarding dysplasia surveillance in BE, some limitations exist, leading to poor adherence. Newer technologies, such as acetic acid-enhanced magnification endoscopy, narrow band imaging, Raman spectroscopy, molecular approaches and the use of artificial intelligence appear promising in addressing these problems, but further studies are required before implementation into routine clinical practice. The Asian Barrett's Consortium also outlines its ongoing plans to tackle the challenge of standardizing the diagnosis of BE in Asia.

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.

Background: This extensive meta-analysis sought to compare the surgical, histological, and oncological outcomes between endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) in the treatment of colorectal polyps, with subgroup analysis comparing the efficacy of ESD and EMR between Japan and the rest of the world. Methods: Embase and Medline databases were searched from inception to October 2020 in accordance with PRISMA guidelines for studies comparing en bloc, complete resection, margin involvement, resection time, need for additional surgery, complications, and recurrence rate of ESD with EMR. Results: 281,344 colorectal polyps from 21 studies were included. When compared to EMR, the pooled analysis revealed ESD was associated with higher en bloc and complete resection rate, and lower lateral margin involvement and recurrence. ESD led to increased procedural time, need for additional surgery, and perforation risk. No significant difference in bleeding risk was found between the two groups. Meta-regression analysis suggested only right colonic polyps correlated with an increased perforation risk in ESD. Confounders including polyp size and invasion depth did not significantly influence the en bloc and complete resection rate, bleeding risk and recurrence. In subgroup analysis, Japan performed better than the rest of the world in both ESD and EMR with perforation risk of 4% and 0.0002%, respectively, as compared to perforation risk of 8% and 1%, respectively, in reports coming from rest of the world.Conclusions: This meta-analysis demonstrated increased safety and efficacy of ESD and EMR done in Japan as compared with the rest of the world.

This paper presents a two magnetic sensor based tracking method for a magnetically inflated intragastric balloon capsule (MIBC) which is used for obesity treatment. After the MIBC is swallowed, it is designed to be inflated inside the stomach by approaching a permanent magnet (PM) externally near the abdomen. However, if the balloon inflation is accidentally triggered while the MIBC is still in the esophagus, the esophagus will be damaged. Therefore, to safely inflate the MIBC, we aim to track the MIBC's position along the esophagus and confirm the MIBC passes through. Typically, magnetic sensor based tracking systems tend to be bulky and costly since they involve computationally intensive optimization with many magnetic sensors. To solve those problems, we develop an algorithm that estimates the position of the PM inside the MIBC by using the grid search combined with the dynamically confined search range and search threshold modulation. Our tracking method achieved an average 1D position error of 3.48 mm which is comparable to the up to 4 mm average error for the other magnetic sensor based tracking systems that require more sensors and computational power compared to our system. Nanyang Technological University This research is supported by Nanyang Technological University (Start up Grant M4081419).

Background Hepatocellular carcinoma with biliary ductal invasion is rare and associated with a significantly lower survival rate. Case presentation We present an unusual case of a patient with hepatocellular carcinoma and biliary invasion, who had his diagnosis confirmed by histological analysis from tissue extracted by endoscopic retrograde cholangiopancreatography. An 87-year-old male presented with a 1-day history of right upper quadrant pain and jaundice. His past medical history included recurrent gallstone cholangitis and a previous cholecystectomy. An abdominal CT demonstrated a dilated intrahepatic biliary tree with left proximal intrahepatic hyperdensities, as well as a 3 cm hepatocellular carcinoma. He was initially suspected to have concurrent gallstone cholangitis and a newly diagnosed hepatocellular carcinoma. Endoscopic retrograde cholangiopancreatography and balloon trawling of the intraductal lesions extracted necrotic tumour-like tissue which was histologically consistent with hepatocellular carcinoma. The extraction of the intra-biliary portion of HCC resulted in complete resolution of his jaundice, enabling further treatment with nivolumab, which would not have been possible if the obstruction was not cleared. The patient is currently well and has completed his 6th cycle of nivolumab. Conclusion Obstructive jaundice is an uncommon presentation for patients with HCC. it is key for clinicians to be aware of the possibility of intrabiliary invasion in order obtain an early diagnosis and to reduce any delay in treatment.

BACKGROUND Major societies provide differing guidance on management of Barrett’s esophagus (BE), making standardization challenging. AIM To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists. METHODS Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis, surveillance and management of BE. RESULTS Five hundred sixty-nine of 1016 (56.0%) respondents completed the survey, with most respondents from Japan (n = 310, 54.5%) and China (n = 129, 22.7%). Overall, the preferred endoscopic landmark of the esophagogastric junction was squamo-columnar junction (42.0%). Distal palisade vessels was preferred in Japan (59.0% vs 10.0%, P < 0.001) while outside Japan, squamo-columnar junction was preferred (59.5% vs 27.4%, P < 0.001). Only 16.3% of respondents used Prague C and M criteria all the time. It was never used by 46.1% of Japanese, whereas 84.2% outside Japan, endoscopists used it to varying extents (P < 0.001). Most Asian endoscopists (70.8%) would survey long-segment BE without dysplasia every two years. Adherence to Seattle protocol was poor with only 6.3% always performing it. 73.2% of Japanese never did it, compared to 19.3% outside Japan (P < 0.001). The most preferred (74.0%) treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis. For BE with low-grade dysplasia, 6-monthly surveillance was preferred in 61.9% within Japan vs 47.9% outside Japan (P < 0.001). CONCLUSION Diagnosis and management of BE varied within Asia, with stark contrast between Japan and outside Japan. Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction, which is incorrect. Most also did not consistently use Prague criteria, and Seattle protocol. Lack of standardization, education and research are possible reasons.

BackgroundDifferentiating between malignant and normal cells within tissue samples is vital for molecular profiling of cancer using advances in genomics and transcriptomics. Cell-surface markers of tumour–normal discrimination have additional value in terms of translatability to diagnostic and therapeutic strategies. In gastric cancer (GC), previous studies have identified individual genes or proteins that are upregulated in cancer. However, a systematic analysis of cell-surface markers and development of a composite panel involving multiple candidates to differentiate tumour from normal has not been previously reported.MethodsWhole transcriptome sequencing (WTS) of GC and matched normal samples from the Singapore Gastric Cancer Consortium (SGCC) was used as a discovery cohort to identify upregulated putative cell-surface proteins. Matched WTS data from the The Cancer Genome Atlas (TCGA) was used as a validation cohort. Promising candidates from this analysis were validated orthogonally using multispectral immunohistochemistry (mIHC) with automated quantitative analysis using the Vectra platform. mIHC was performed on a tissue microarray containing matched normal, marginal and tumour tissues. The receiver-operating characteristic (ROC) curves were analysed to identify markers with the highest diagnostic validity independently and in combination.ResultsAnalysis of putative membrane protein transcripts from the SGCC discovery cohort WTS data (n=15 matched tumour and normal pairs) identified several differentially and highly expressed candidates in tumour compared with normal tissues. After validation with TCGA data (n=29 matched tumour and normal pairs), the following proteins were selected for mIHC analysis: CEACAM5, CEACAM6, CLDN4, CLDN7, and EpCAM. These were compared with established glycoprotein markers in GC, namely CA19-9 and CA72-4. Individual ROC curves yielded the best performance for CEACAM5 (area under the ROC curve (AUC)=0.80), CEACAM6 (AUC=0.82), EpCAM (AUC=0.83), and CA72-4 (AUC=0.76). Combined multiplexed imaging of these four markers revealed improved specificity and sensitivity for detection of tumour from normal tissue (AUC of 4-plex=0.91).ConclusionCEAMCAM5, CEACAM6, EpCAM, and CA72-4 form a versatile set of markers for robust discrimination of GC from adjacent normal tissue. As cell-surface markers, they are compatible with both IHC and live imaging approaches. These candidates may be exploited to improve automated identification of tumour tissue in GC.

Endoscopic ultrasound (EUS) has evolved to be a key tool in the management of gastrointestinal conditions, and is particularly useful in the management of gastrointestinal malignancy, where the stage depends on the depth of invasion, as well as malignant involvement of locoregional lymph nodes, which besides visualization, can be sampled by concurrent fine-needle aspiration or biopsy.

Background Although endoscopic ultrasound (EUS) features and criteria have been described in chronic pancreatitis, challenges remain with interoperator variability and ease of adoption. The aim of this study was to define and validate the EUS features of chronic pancreatitis in a multicenter prospective study in Asia. Method The study was divided into two parts: the first part was conducted to derive the EUS features of chronic pancreatitis with adequate interoperator agreement; the second was to prospectively evaluate these features in a multicenter cross-sectional study and determine the optimal combination of features for the diagnosis of chronic pancreatitis. Prospectively enrolled cases had standard internationally validated radiologic or histologic features of chronic pancreatitis, and controls were patients without chronic pancreatitis who underwent EUS examination. Results The top six EUS features that had good interobserver agreement (mean kappa 0.73, range 0.60 – 0.90) were selected to be further evaluated in part II of the study. These included: hyperechoic foci with shadowing, lobularity with honeycombing, cysts, dilated main pancreatic duct, dilated side branches, and calculi in the main pancreatic duct. A total of 284 subjects (132 cases, 152 controls) were enrolled from 12 centers in Asia. All six features had high accuracy ranging from 63.3 % to 89.1 %. Two or more of these six EUS features accurately defined chronic pancreatitis (sensitivity 94.7 %, specificity 98.0 %), with an area under the receiver operating curve of 0.986. Conclusion This multicenter Asian study characterized and defined the EUS features of chronic pancreatitis. This provides a useful tool in clinical practice and further research in pancreatic cancer surveillance.

Traditionally, suturing is performed in open surgery using a needle holder and forceps. The aim is to achieve accurate approximation of both edges of the wound and to tie a secure knot. With the development of laparoscopic surgery, traditional suturing methods have been adapted to meet the constraints of rigid laparoscopic instruments with limited degrees of freedom. The subsequent introduction of three-dimensional robotic suturing has since made intracorporeal suturing easier to learn, primarily because of its intuitiveness and the additional degree of freedom of the robotic wrists. With the increasing popularity of therapeutic endoscopic procedures for early gastrointestinal cancers, devices allowing for endoscopic suturing have since been developed. Nevertheless, these devices remain challenging to use as they require double-channel endoscopes and do not have the extra degree of freedom of robotic wrists. The introduction of robotics to the field of endoscopic suturing has proven to be promising. This review describes the development and adaptation of basic suturing techniques to various platforms, such as laparoscopic, robotic and endoscopic.

Background and Aims One of the difficulties in performing endoscopic submucosal dissection (ESD) is the lack of retraction during submucosal dissection. The development of the EndoMaster EASE System (EndoMaster Pte Ltd, Singapore) aims to enhance the safety and efficacy of ESD through 2 flexible robotic arms for tissue retraction and dissection. This is a preclinical animal study to evaluate the performance of colorectal ESD using the latest version of the EndoMaster EASE System. Methods The latest version of the EndoMaster EASE System consists of an independently designed, flexible platform with a built-in endoscopic imaging system and 3 working channels, 2 for the passage of robotic arms and 1 for accessories. In this animal study, the outcome measures were operating time (from starting incision to finishing dissection), completeness of resection, procedure-related adverse events, and limitations of arm manipulation in a narrow working space as assessed by counting the frequency of blind cutting. Results Five ESD procedures were performed in a 66.7-kg porcine model with the animal under general anesthesia. The mean operative time was 73.8 minutes, and the mean size of the specimen resected was 1340 mm2. There was no perforation, although profuse bleeding was encountered during 1 robotic ESD procedure. Conclusions The current preclinical study confirmed the feasibility of performing colorectal ESD using the latest version of the EndoMaster EASE System. The system was also tested for the ability to manage adverse events including bleeding and perforation. This study provided important preclinical experience for clinical trial.

To study the impact of computer-aided detection (CADe) system on the detection rate of polyps and adenomas in colonoscopy.A total of 1026 patients were prospectively randomly scheduled for colonoscopy with (the CADe group, CADe) or without (the control group, CON) the aid of the CADe system, together with visual notification and voice alarm, so as to compare the detection rate of polyp.Compared with group CON, the detection rate of adenomas increased in group CADe, the average number of adenomas increased, the number of small adenomas increased, the number of proliferative polyps increased, and the differences were statistically significant (P0.001), but the comparison for the number of larger adenomas showed no significant difference between the groups (P0.05).The CADe system is feasible for increasing the detection of polyps and adenomas in colonoscopy.

Although colonoscopy was originally a diagnostic imaging procedure, it has now expanded to include an increasing range of therapeutic interventions. These procedures require precise maneuvers of instruments, execution of force, efficient transmission of force from the operator to the point of application, and sufficient dexterity in the mobilization of endoscopic surgical instruments. The conventional endoscope is not designed to support technically demanding endoscopic procedures. In case of colonoscopy, the tortuous anatomy of the colon makes inserting, moving, and orientating the endoscope difficult. Exerting excessive pressure can cause looping of the endoscope, pain to the patient, and even perforation of the colon. To mitigate the technical constraints, numerous technically enhanced systems have been developed to enable better control of instruments and precise delivery of force in the execution of surgical tasks such as apposing, grasping, traction, counter-traction, and cutting of tissues. Among the recent developments are highly dexterous robotic master and slave systems, computer-assisted or robotically enhanced conventional endoscopes, and autonomously driven locomotion devices that can effortlessly traverse the colon. Developments in endoscopic instrumentations have overcome technical barriers and opened new horizons for further advancements in therapeutic interventions. This review describes examples of some of these systems in the context of their applications to advanced therapeutic colonoscopy.

A significant proportion of the non-alcoholic fatty liver disease (NAFLD) population is non-obese. Prior studies reporting the severity of NAFLD amongst non-obese patients were heterogenous. Our study, using data from the largest biopsy-proven NAFLD international registry within Asia, aims to characterize the demographic, metabolic and histological differences between non-obese and obese NAFLD patients.1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients.One-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01-2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99-3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p 0.001) when classifying patients with F2-4 fibrosis amongst non-obese NAFLD patients. Haemoglobin, GGT, waist circumference and cholesterol are additional variables found on random forest analysis useful for identifying non-obese NAFLD patients with advanced liver disease.A substantial proportion of non-obese NAFLD patients has NASH or advanced fibrosis. FIB-4, compared to NFS better identifies non-obese NAFLD patients with advanced liver disease. Serum GGT, cholesterol, haemoglobin and waist circumference, which are neither components of NFS nor FIB-4, are important biomarkers for advanced liver disease in non-obese patients.

BACKGROUND The Gut and Obesity Asia (GO ASIA) workgroup was formed to study the relationships between obesity and gastrointestinal diseases in the Asia Pacific region. AIM To study factors associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis, and medical treatment of biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients. METHODS Retrospective study of biopsy-proven NAFLD patients from centres in the GO ASIA Workgroup. Independent factors associated with NASH and with advanced fibrosis on binary logistic regression analyses in a training cohort were used for the development of their corresponding risk score, which were validated in a validation cohort. RESULTS We included 1008 patients from nine centres across eight countries (NASH 62.9%, advanced fibrosis 17.2%). Independent predictors of NASH were body mass index ≥30 kg/m2 , diabetes mellitus, dyslipidaemia, alanine aminotransferase ≥88 U/L and aspartate aminotransferase ≥38 U/L, constituting the Asia Pacific NASH risk score. A high score has a positive predictive value of 80%-83% for NASH. Independent predictors of advanced fibrosis were age ≥55 years, diabetes mellitus and platelet count

Drainage of obstructed bile duct and pancreatic duct under endoscopic ultrasonography (EUS) guidance has evolved into viable techniques suitable for patients with failed endoscopic retrograde cholangiopancreatography (ERCP) and/or altered surgical anatomy. One of the major advantages of EUS guidance is the possibility of multiple access points depending upon patient and ductal anatomy. Unlike ERCP, an approachable papilla is not a requisite for successful EUS-guided biliary or pancreatic ductal drainage. Moreover, as the access is away from the papilla, there is the possibility of reduced pancreatitis. A variety of procedures have become available for EUS-guided drainage, and it is important to develop standard terminology and procedural details. EUS-specific stents, including lumen-apposing metal stents have recently become available, and are likely to impact the outcomes of these procedures. Available data show a high success rate and acceptable adverse event rate for EUS-guided biliary drainage. Success rate appears to be low for pancreatic duct drainage because of a variety of reasons. Outcomes of EUS-guided biliary drainage appear equivalent to percutaneous drainage and ERCP. EUS-guided gallbladder drainage appears promising for patients requiring gallbladder drainage but unfit for surgery. Further large controlled studies are needed to evaluate the exact role of these procedures.

Background The Gut and Obesity in Asia (GOASIA) Workgroup was formed to study obesity and gastrointestinal diseases in the Asia Pacific region. We aimed to 1) compare the characteristics of elderly (i.e. age ≥ 60) vs. non-elderly patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD); 2) identify predictors of advanced fibrosis in elderly patients with NAFLD; and 3) assess the performance of non-invasive fibrosis scores in the prediction of advance fibrosis in the elderly population. Methods We abstracted the data of 1008 patients with NAFLD from nine centers across eight countries. Characteristics of elderly and non-elderly patients with NAFLD were compared using 1:3 sex-matched analysis. Results Of the 1008 patients, 175 were elderly [age 64 (62–67) years], who were matched with 525 non-elderly patients [46 (36–54) years]. Elderly patients were more likely to have advanced fibrosis (35.4% vs. 13.3%; p Conclusions Elderly patients with NAFLD had a higher prevalence of advanced fibrosis than non-elderly patients. Female and hypertension were predicting factors for advanced fibrosis in the elderly. Non-invasive fibrosis scores had a lower specificity in elderly.

Objective Intestinal metaplasia (IM) is a premalignant stage that poses a greater risk for subsequent gastric cancer (GC). However, factors regulating IM to GC progression remain unclear. Previously, activated DNA damage response (DDR) signalling factors were shown to engage tumour-suppressive networks in premalignant lesions. Here, we interrogate the relationship of DDR signalling to mutational accumulation in IM lesions. Design IM biopsies were procured from the gastric cancer epidemiology programme, an endoscopic surveillance programme where biopsies have been subjected to (epi)genomic characterisation. IM samples were classified as genome-stable or genome-unstable based on their mutational burden/somatic copy-number alteration (CNA) profiles. Samples were probed for DDR signalling and cell proliferation, using the markers γH2AX and MCM2, respectively. The expression of the gastric stem cell marker, CD44v9, was also assessed. Tissue microarrays representing the GC progression spectrum were included. Results MCM2-positivity increased during GC progression, while γH2AX-positivity showed modest increase from normal to gastritis and IM stages, with further increase in GC. γH2AX levels correlated with the extent of chronic inflammation. Interestingly, genome-stable IM lesions had higher γH2AX levels underscoring a protective anti-cancer role for DDR signalling. In contrast, genome-unstable IM lesions with higher mutational burden/CNAs had lower γH2AX levels, elevated CD44v9 expression and modest promoter hypermethylation of DNA repair genes WRN, MLH1 and RAD52. Conclusions Our data suggest that IM lesions with active DDR will likely experience a longer latency at the premalignant state until additional hits that override DDR signalling clonally expand and promote progression. These observations provide insights on the factors governing IM progression.

Barrett's oesophagus is a pre-malignant condition associated with the development of oesophageal adenocarcinoma. Currently white light endoscopy and biopsy is the mainstay diagnostic tool. Yet this approach is troubled by issues related to cumbersome biopsy sampling, biopsy sampling errors and cost. Therefore in order to overcome such adversity, there needs to be evolutionary advancement in terms of diagnosis, which should address these concerns and ideally enhance risk stratification in order to provide timely management in real time. This review highlights the current endoscopic tools aimed to enhance the diagnosis of Barrett's oesophagus and its subsequent progression.

Background/Aims The prevalence of irritable bowel syndrome (IBS) has risen considerably over the past decade in Singapore. We aim to explore the contribution of changes in diet, lifestyle and habits that may contribute to the increased prevalence and development of IBS. Methods This is a survey-based cross-sectional population study aimed to gather demographic, socio-economical, lifestyle, dietary, antibiotic usage and other related information. Subjects were adult male or female Singaporeans aged 21 years or above. Association of the factors gathered with the presence or absence of IBS (by Rome III criteria) was assessed using chi-square or Fisher’s exact test. Variables with a level of statistical significance of 0.1 or less in the univariate analysis were entered into a stepwise logistic regression model. Results A total of 297 subjects participated in the study (female 60.3%). Overall, 20.9% subjects fulfilled the Rome III IBS criteria. Univariate analysis showed that IBS was associated with pet ownership, antibiotic usage, late dinner, (> 9 PM) and consumption of Western meals, coffee, and bread. The multivariate logistic regression analyses showed that IBS was independently associated with being a pet owner (P = 0.008; OR, 2.5; 95% CI, 1.278–5.037). Conclusions The prevalence of IBS was 20.9% using the Rome III criteria in our study. The association between IBS and pet ownership will need further investigation.

Endoscopic ultrasound-guided biliary drainage (EUS-BD) is emerging as a safe and effective alternative for endoscopic BD. The advantage of multiple access points from stomach and duodenum allows EUS-BD in patients with altered surgical anatomy and duodenal stenosis. EUS-BD is also useful in patients with failed endoscopic retrograde cholangiopancreatography or difficult biliary cannulation. Depending on the access and exit route of the stent, a variety of EUS-BD procedures have been described. Trans-papillary as well as trans-luminal stent placements are possible with EUS-BD. Recent studies have shown a clinical success rate in excess of 90% and complication rates of < 15%. Prospective studies are needed to know the long-term results and relative efficacy of this technique.

Drainage of pseudocyst and walled-off pancreatic necrosis has traditionally been achieved by surgical means. Recently, there has been a progressive shift in paradigm to performing endoscopic drainage for these conditions. Endoscopic ultrasound (EUS)-guided drainage is the preferred approach for drainage of pancreatic pseudocyst. However, many controversies still exist on the optimal management and wide variations in techniques exist. There is a pressing need for establishment of a consensus for safe practices in EUS-guided pseudocyst drainage.

Globally white-light endoscopy with biopsy sampling is the gold standard diagnostic modality for esophageal, gastric, and colonic pathologies. However, there is overwhelming evidence to highlight the deficiencies of an approach based predominantly on eyeball visualization. Biopsy sampling is also problematic due in part to excessive sampling and hence attendant cost. Various innovations are currently taking place in the endoscopic domain to aid operators in diagnosis forming. These include narrow band imaging which aims to enhance the surface anatomy and vasculature, and confocal laser endomicroscopy which provides real time histological information. However, both of these tools are limited by the skill of the operator and the extensive learning curve associated with their use. There is a gap therefore for a new form of technology that relies solely on an objective measure of disease and reduces the need for biopsy sampling. Raman spectroscopy (RS) is a potential platform that aims to satisfy these criteria. It enables a fingerprint capture of tissue in relation to the protein, DNA, and lipid content. This focused review highlights the strong potential for the use of RS during endoscopic gastroenterological examination.

The incidence of obesity is increasing in Asia, with implications on gastrointestinal (GI) and liver diseases. The Gut and Obesity in Asia Workgroup comprises regional experts with the aim of studying relationship between obesity and the GI and liver diseases in Asia. Through literature review and the modified Delphi process, consensus statements examining the impact of obesity on esophageal, gastric, pancreatic, colorectal, and liver diseases, exploring relationship between gut microbiome and obesity, and assessing obesity therapies have been produced by the Gut and Obesity in Asia Workgroup. Sixteen experts participated with 9/15 statements having strong consensus (>80% agreement). The prevalence of obesity in Asia is increasing (100% percentage agreement in brackets), and this increased prevalence of obesity will result in a greater burden of obesity-related GI and liver diseases (93.8%). There was consensus that obesity increases the risk of gastric cancer (75%) and colorectal neoplasia (87.5%). Obesity was also associated with Barrett's esophagus and esophageal adenocarcinoma (66.7%) and pancreatic cancer (66.7%) in Asia. The prevalence of non-alcoholic fatty liver disease (NAFLD) in Asia is on the rise (100%), and the risk of NAFLD in Asia (100%) is increased by obesity. Obesity is a risk factor for the development of hepatocellular carcinoma (93.8%). Regarding therapy, it was agreed that bariatric surgery was an effective treatment modality for obesity (93.8%) but there was less agreement on its benefit for NAFLD (62.5%). These experts' consensus on obesity and GI diseases in Asia forms the basis for further research, and its translation into addressing this emerging issue.

Full-thickness gastrointestinal defects such as perforation, anastomotic leak, and fistula are severe conditions caused by various types of pathologies. They are more likely to require intensive care and a long hospital stay and have high rates of morbidity and mortality. After intentional full-thickness opening of hollow organs for natural orifice transluminal endoscopic surgery, safe and secure closure is urgently required. The currently available advanced endoscopic closing techniques have a major role in the treatment of full-thickness gastrointestinal defects. Appropriate usage of these techniques requires taking into account their advantages and limitations during practical application. We reviewed the available endoscopic modalities, including endoscopic clips, stents, vacuum-assisted closure, gap filling, and suturing devices, discussed their advantages and limitations when treating full-thickness gastrointestinal defects, and explored emerging innovations, including a novel endoluminal surgical platform for versatile suturing and a cell-laden scaffold for effective gap filling. Although these emerging technologies still require further pre-clinical and clinical trials to assess their feasibility and efficacy, the available modalities may be replaced and refined by these new techniques in the near future.

// Rony K. Roy 1, * , Michal M. Hoppe 1, * , Supriya Srivastava 1 , Animesh Samanta 2 , Neel Sharma 3 , Kar Tong Tan 1 , Henry Yang 1 , Dominic C. Voon 1 , Brendan Pang 4 , Ming Teh 4 , Naoko Murata-Kamiya 5 , Masanori Hatakeyama 5 , Young-Tae Chang 2 , Wei Peng Yong 1, 6 , Yoshiaki Ito 1, 6 , Khek Yu Ho 2, 6 , Patrick Tan 1, 6 , Richie Soong 1 , Phillip H. Koeffler 1, 2 , Khay Guan Yeoh 2, 6 , Anand D. Jeyasekharan 1, 6 1 Cancer Science Institute of Singapore, National University of Singapore, Singapore 2 Department of Chemistry, National University of Singapore, Singapore 3 Division of Gastroenterology and Hepatology, National University Hospital, Singapore 4 Department of Pathology, National University Hospital, Singapore 5 University of Tokyo, Tokyo, Japan 6 Singapore Gastric Cancer Consortium, National University of Singapore, Singapore * These authors have contributed equally to this work Correspondence to: Khay Guan Yeoh, email: mdcykg@nus.edu.sg Anand D. Jeyasekharan, email: csiadj@nus.edu.sg Keywords: gastric cancer, biomarker, Helicobacter pylori, CEACAM6, endoscopy Received: February 19, 2016 Accepted: May 23, 2016 Published: July 11, 2016 ABSTRACT Early detection of gastric cancers saves lives, but remains a diagnostic challenge. In this study, we aimed to identify cell-surface biomarkers of early gastric cancer. We hypothesized that a subset of plasma membrane proteins induced by the Helicobacter pylori oncoprotein CagA will be retained in early gastric cancers through non-oncogene addiction. An inducible system for expression of CagA was used to identify differentially upregulated membrane protein transcripts in vitro . The top hits were then analyzed in gene expression datasets comparing transcriptome of gastric cancer with normal tissue, to focus on markers retained in cancer. Among the transcripts enriched upon CagA induction in vitro , a significant elevation of CEACAM6 was noted in gene expression datasets of gastric cancer. We used quantitative digital immunohistochemistry to measure CEACAM6 protein levels in tissue microarrays of gastric cancer. We demonstrate an increase in CEACAM6 in early gastric cancers, when compared to matched normal tissue, with an AUC of 0.83 for diagnostic validity. Finally, we show that a fluorescently conjugated CEACAM6 antibody binds avidly to freshly resected gastric cancer xenograft samples and can be detected by endoscopy in real time. Together, these results suggest that CEACAM6 upregulation is a cell surface response to H. pylori CagA, and is retained in early gastric cancers. They highlight a novel link between CEACAM6 expression and CagA in gastric cancer, and suggest CEACAM6 to be a promising biomarker to aid with the fluorescent endoscopic diagnosis of early neoplastic lesions in the stomach.

Several EUS-specific stents have become available. It has been claimed that some of these stents have lumen-apposing properties, but objective data measuring such properties are not available. The aim of this study is to measure the lumen-apposing force (LAF) of these stents.The LAF of 3 EUS-specific metallic stents (stents A, N, and S) were compared in an ex vivo setting. Four types of anastomoses were performed with the stents including cholecysto-duodenal, cholecysto-gastric, gastro-gastric, and gastro-jejunal and compared with a hand-sewn (HS) equivalent of the anastomosis. The outcome parameter was the LAF created by each type of stent.Sixty-four anastomoses were created. The overall mean (standard deviation) LAFs were significantly higher for stents A and S (P .001). This difference persisted regardless of the type of anastomosis: gastro-gastric (P = .002), gastro-jejunal (P = .005), cholecysto-gastric (P = .002), and cholecysto-jejunal (P = .003). The differences in LAF created by each type of stent across different types of anastomoses were also compared. A trend to significance was observed in the anastomoses created by stent N (P = .064) and stent A (P =.052); a significant difference in LAF was observed among different anastomoses created by stent S (P = .015). The LAF created by HS anastomosis was significantly higher than that for all stents across all anastomoses.Stents A and S had a higher LAF. The use of these stents should be considered when performing EUS-guided transmural luminal anastomoses in non-adherent organs. Further studies are required to confirm the clinical efficacies of these EUS-specific stents.

We report a unique simultaneous fingerprint (FP) and high-wavenumber (HW) Raman spectroscopy technique coupled with a beveled fiber-optic Raman probe for improving in vivo detection of gastric intestinal metaplasia (IM)–precancerous lesions in real-time during clinical gastroscopy. A total of 4,520 high-quality in vivo FP/HW gastric Raman spectra (normal = 4,178; IM = 342) were acquired from 157 gastric patients undergoing endoscopic examination. Multivariate diagnostic algorithms based on principal components analysis and linear discriminant analysis together with the leave-one tissue site-out, cross-validation on in vivo tissue Raman spectra yield the diagnostic sensitivities of 89.3%, 89.3%, and 75.0%; specificities of 92.2%, 84.4%, and 82.0%; positive predictive values of 52.1%, 35.2%, and 28.4%; and negative predictive values of 98.9%, 98.8%, and 97.2%, respectively, by using the integrated FP/HW, FP, and HW Raman techniques for identifying IM from normal gastric tissue. Further, ROC curves generated show that the integrated FP/HW Raman technique gives the integration area under the ROC curve of 0.92 for IM classification, which is superior to either FP (0.89) or HW Raman (0.86) technique alone. This work demonstrates for the first time that the simultaneous FP/HW fiber-optic Raman spectroscopy has great potential to enhance early diagnosis of gastric precancer in vivo during routine endoscopic examination. Cancer Prev Res; 9(6); 476–83. ©2016 AACR.

The incidence of esophageal adenocarcinoma is rapidly increasing in Western countries. This is despite the introduction of sophisticated endoscopic techniques and our ability to readily monitor the presumed precursor lesion known as Barrett’s esophagus. Preemptive approaches, including radiofrequency ablation (RFA), and photodynamic therapy (PDT) for Barrett’s esophagus and dysplasia are achieving dramatic initial results. Although the long-term efficacy of these nonspecific ablative therapies is awaiting longitudinal studies, reports of recurrences are increasing. More targeted therapies, particularly directed at the stem cells of Barrett’s esophagus, demand knowing the origin of this intestinal metaplasia (IM). The prevailing concept holds that Barrett’s esophagus arises from the “transcommitment” of esophageal stem cells to produce an intestine-like epithelium. An alternative explanation derives from the discovery of a discrete population of residual embryonic cells (RECs) existing at the gastroesophageal junction in normal individuals that expands and colonizes regions of the esophagus denuded by chronic reflux. These RECs form IM within days of esophageal injury, suggesting a novel mechanism of tumorigenesis.

Background & Aims Measuring liver stiffness only in patients with indeterminate or high nonalcoholic fatty liver disease (NAFLD) fibrosis scores (called a 2-step approach) was reported to reduce indeterminate or discordant results while maintaining the accuracy to identify patients with advanced fibrosis. We aimed to validate this approach using data collected from the Gut and Obesity in Asia Workgroup. Methods We performed a retrospective analysis of data from 759 patients with biopsy-proven NAFLD (24% with advanced fibrosis), seen at 10 centers in 9 countries in Asia, from 2006 through 2018. By using liver biopsies as the reference standard, we calculated percentages of misclassifications and indeterminate or discordant results from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis-4 score) and liver stiffness measurements (LSMs), alone or in combination. The analysis was repeated using randomly selected subgroups with a different prevalence of advanced fibrosis (histologic fibrosis stage ≥F3). Results In groups in which 3.7% and 10% of patients had advanced fibrosis, a 2-step approach (using the NFS followed by LSM only for patients with indeterminate or high NFS) and using a gray zone of 10 to 15 kPa for LSM, produced indeterminate or discordant results for 6.9% of patients and misclassified 2.7% of patients; only 25.6% of patients required LSM. In the group in which 10% of patients had advanced fibrosis, the same approach produced indeterminate or discordant results for 7.9% of patients and misclassified 6.6% of patients; only 27.4% of patients required LSM. In groups in which 24% and 50% of patients had advanced fibrosis, using LSM ≥10 kPa alone for the diagnosis of advanced fibrosis had the highest accuracy and misclassified 18.1% and 18.3% of patients, respectively. These results were similar when the Fibrosis-4 score was used in place of NFS. Conclusions In a retrospective analysis, we found that a 2-step approach using fibrosis scores followed by LSM most accurately detects advanced fibrosis in populations with a low prevalence of advanced fibrosis. However, LSM ≥10 kPa identifies patients with advanced fibrosis with the highest level of accuracy in populations with a high prevalence of advanced fibrosis.