Prospective single-arm trial on feasibility and safety of endoscopic robotic system for colonic endoscopic submucosal dissection.

Introduction The development of EndoMaster EASE system aims to enhance safety and efficacy of colonic ESD through two flexible robotic arms for tissue retraction and dissection. This is the first clinical trial to evaluate the performance of colorectal ESD using EndoMaster. Method Patients with early mucosal colorectal neoplasia not feasible for en-bloc resection with snare-based techniques were recruited. The EndoMaster EASE robotic system consisted of an independently designed flexible robotic platform with 2 robotic arms. The primary outcome was complete resection rate using EndoMaster. Secondary outcomes included operating time, hospital stay, procedure-related complications and oncological outcomes. Results From May 2020 to Jan 2022, 43 patients received robotic ESD with median age of 66 years (40-83). The mean robotic dissection time was 62.0 ± 45.1 minutes. All procedures except six were completed using EndoMaster with technical success rate of 86.1% (37/43). The en-bloc resection rate among cases with technical success was 94.6% (35/37) while the complete resection rate was 83.8% (31/37). The median size of specimen was 35mm (15-90mm). The mean hospital stay was 2.6 ± 1.2 days and there was one delayed bleeding 4 days after ESD which was controlled by endoscopy. One patient sustained perforation during procedure which was completely closed using clips without sequelae. 2 patients required salvage surgery due to deep margin involvement by adenocarcinoma in histopathology. Conclusion This first clinical trial confirmed the safety and efficacy of performing colorectal ESD using EndoMaster EASE robotic system (Clinicaltrial.gov: NCT04196062).

Partially covered versus uncovered pyloro-duodenal stents for unresectable malignant gastric outlet obstruction: Randomized controlled study.

OBJECTIVES: The aim of the current study was to compare the efficacy of partially covered duodenal stent (PCDS) vs. uncovered duodenal stent (UCDS) in patients suffering from unresectable primary malignant gastric outlet obstruction (GOO). METHODS: This was a prospective international randomized controlled study conducted in 10 high-volume institutions. Consecutive patients suffering from malignant GOO were recruited. The primary outcome measurement was the reintervention rate. Secondary outcomes included technical and clinical success, 30-day adverse events, 30-day mortality, causes of stent dysfunction, and the duration of stent patency. RESULTS: Between March 2017 and October 2020, 115 patients (59 PCDS, 56 UCDS) were recruited. The 1-year reintervention was not significantly different (PCDS vs. UDCS = 12/59, 20.3% vs. 14/56, 25%, P = 0.84). There was a trend to fewer patients with tumor ingrowth in the PCDS group (6/59 [10.2%]) vs. 13/56 [23.2%], P = 0.07). There were no significant differences in the technical success (100% vs. 100%, P = 1), clinical success (91.5% vs. 98.2%, P = 0.21), procedural time (21.5 [interquartile range [IQR] 17-30] vs. 20.0 [IQR 15-34.75], P = 0.62), hospital stay (4 [IQR 3-12] vs. 5 [IQR 3-8] days, P = 0.81), 30-day adverse events (18.6% vs. 14.3%, P = 0.62), or 30-day mortality (6.8% vs. 5.2%, P = 1.00). CONCLUSION: The use of PCDS was associated with a lower risk of tumor ingrowth but did not improve on reintervention rates or stent patency. Both kinds of stents could be used in this group of patients.

Impact of COVID-19 infection and vaccination in pancreatobiliary IgG4-related disease patients: An international multicenter study.

BACKGROUND AND AIM: Dedicated studies evaluating the impact of COVID-19 on outcomes of pancreatobiliary IgG4 related disease (IgG4-RD) patients are scarce. Whether COVID-19 infection or vaccination would trigger IgG4-RD exacerbation remains unknown. METHODS: Pancreatobiliary IgG4-RD patients ≥ 18 years old with active follow-up since January 2020 from nine referral centers in Asia, Europe, and North America were included in this multicenter retrospective study. Outcome measures include incidence and severity of COVID-19 infection, IgG4-RD disease activity and treatment status, interruption of indicated IgG4-RD treatment. Prospective data on COVID-19 vaccination status and new COVID-19 infection during the Omicron outbreak were also retrieved in the Hong Kong cohort. RESULTS: Of the 124 pancreatobiliary IgG4-RD patients, 25.0% had active IgG4-RD, 71.0% were on immunosuppressive therapies and 80.6% had ≥ 1 risk factor for severe COVID. In 2020 (pre-vaccination period), two patients (1.6%) had COVID-19 infection (one requiring ICU admission), and 7.2% of patients had interruptions in indicated immunosuppressive treatment for IgG4-RD. Despite a high vaccination rate (85.0%), COVID-19 infection rate has increased to 20.0% during Omicron outbreak in the Hong Kong cohort. A trend towards higher COVID-19 infection rate was noted in the non-fully vaccinated/unvaccinated group (17.6% vs 33.3%, P = 0.376). No IgG4-RD exacerbation following COVID-19 vaccination or infection was observed. CONCLUSION: While a low COVID-19 infection rate with no mortality was observed in pancreatobiliary IgG4-RD patients in the pre-vaccination period of COVID-19, infection rate has increased during the Omicron outbreak despite a high vaccination rate. No IgG4-RD exacerbation after COVID-19 infection or vaccination was observed.

Beyond images: Emerging role of Raman spectroscopy-based artificial intelligence in diagnosis of gastric neoplasia.

White-light endoscopy with tissue biopsy is the gold standard interface for diagnosing gastric neoplastic lesions. However, misdiagnosis of lesions is a challenge because of operator variability and learning curve issues. These issues have not been resolved despite the introduction of advanced imaging technologies, including narrow band imaging, and confocal laser endomicroscopy. To ensure consistently high diagnostic accuracy among endoscopists, artificial intelligence (AI) has recently been introduced to assist endoscopists in the diagnosis of gastric neoplasia. Current endoscopic AI systems for endoscopic diagnosis are mostly based upon interpretation of endoscopic images. In real-life application, the image-based AI system remains reliant upon skilful operators who will need to capture sufficiently good quality images for the AI system to analyze. Such an ideal situation may not always be possible in routine practice. In contrast, non-image-based AI is less constraint by these requirements. Our group has recently developed an endoscopic Raman fibre-optic probe that can be delivered into the gastrointestinal tract via the working channel of any endoscopy for Raman measurements. We have also successfully incorporated the endoscopic Raman spectroscopic system with an AI system. Proof of effectiveness has been demonstrated in in vivo studies using the Raman endoscopic system in close to 1,000 patients. The system was able to classify normal gastric tissue, gastric intestinal metaplasia, gastric dysplasia and gastric cancer, with diagnostic accuracy of >85%. Because of the excellent correlation between Raman spectra and histopathology, the Raman-AI system can provide optical diagnosis, thus allowing the endoscopists to make clinical decisions on the spot. Furthermore, by allowing non-expert endoscopists to make real-time decisions as well as expert endoscopists, the system will enable consistency of care.

Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction.

OBJECTIVE: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ. DESIGN: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised. RESULTS: Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO). CONCLUSIONS: This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

Global variations in diagnostic guidelines for Barrett's esophagus.

Endoscopic diagnosis of gastroesophageal junction and Barrett's esophagus is essential for surveillance and early detection of esophageal adenocarcinoma and esophagogastric junction cancer. Despite its small size, the gastroesophageal junction has many inherent problems, including marked differences in diagnostic methods for Barrett's esophagus in international guidelines. To define Barrett's esophagus, gastroesophageal junction location should be clarified. Although gastric folds and palisade vessels are landmarks for identifying this junction, they are sometimes difficult to observe due to air entry or reflux esophagitis. The possibility of diagnosing a malignancy associated with Barrett's esophagus <1 cm, identified using palisade vessels, should be re-examined. Nontargeted biopsies of Barrett's esophagus are commonly used to detect intestinal metaplasia, dysplasia, and cancer as described in the Seattle protocol. Barrett's esophagus with intestinal metaplasia has a high risk of becoming cancerous. Furthermore, the frequency of cancer in patients with Barrett's esophagus without intestinal metaplasia is high, and the guidelines differ on whether to include the presence of intestinal metaplasia in the diagnosis of Barrett's esophagus. Use of advanced imaging technologies, including narrow-band imaging with magnifying endoscopy and linked color imaging, is reportedly valid for diagnosing Barrett's esophagus. Furthermore, artificial intelligence has facilitated the diagnosis of Barrett's esophagus through its deep learning and image recognition capabilities. However, it is necessary to first use the endoscopic definition of the gastroesophageal junction, which is common in all countries, and then elucidate the characteristics of Barrett's esophagus in each region, for example, length differences in the risk of carcinogenesis with and without intestinal metaplasia.

Is underwater endoscopic mucosal resection of colon polyps superior to conventional techniques? A network analysis of endoscopic mucosal resection and submucosal dissection.

Background and study aims Evidence from recent trials comparing conventional endoscopic mucosal resection (EMR) to underwater EMR (UEMR) have matured. However, studies comparing UEMR to endoscopic submucosal dissection (ESD) are lacking. Hence, we sought to conduct a comprehensive network meta-analysis to compare the efficacy of UEMR, ESD, and EMR. Methods Embase and Medline databases were searched from inception to December 2020 for articles comparing UEMR with EMR and ESD. Outcomes of interest included rates of en bloc and complete polyp resection, risk of perforation and bleeding, and local recurrence. A network meta-analysis comparing all three approaches was conducted. In addition, a conventional comparative meta-analysis comparing UEMR to EMR was performed. Analysis was stratified according to polyp sizes (< 10 mm, ≥ 10 mm, and ≥ 20 mm). Results Twenty-two articles were included in this study. For polyps ≥ 10 mm, UEMR was inferior to ESD in achieving en bloc resection ( P  = 0.02). However, UEMR had shorter operating time for polyps ≥ 10 mm ( P  < 0.001), and ≥20 mm ( P  = 0.019) with reduced perforation risk for polyps ≥ 10 mm ( P  = 0.05) compared to ESD. In addition, en bloc resection rates were similar between UEMR and EMR, although UEMR had reduced recurrence for polyps ≥ 10 mm ( P  = 0.013) and ≥ 20 mm ( P  = 0.014). UEMR also had shorter mean operating than EMR for polyps ≥ 10 mm ( P  < 0.001) and ≥ 20 mm ( P  < 0.001). Risk of bleeding and perforation with UEMR and EMR were similar for polyp of all sizes. Conclusions UEMR has demonstrated technical and oncological outcomes comparable to ESD and EMR, along with a desirable safety profile. UEMR appears to be a safe and effective alternative to conventional methods for resection of polyps ≥ 10 mm.

Non-obese non-alcoholic fatty liver disease (NAFLD) in Asia: an international registry study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. CONCLUSION: 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.

Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP).

OBJECTIVE: To 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. METHODS: A 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). RESULTS: There 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; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III-IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III-IV developed within 2 years (range: 12.7-44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III-IV if they are negative for H. 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. CONCLUSIONS: We 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.

Changing perspectives in the training of endoscopic ultrasonography in Asia.

Training of endoscopic ultrasound (EUS) in Asia faces challenges of the ever-increasing demand for skills to handle a growing range of both diagnostic and interventional EUS procedures, and a continual shortage of EUS training programs. To keep up with the pace of development in EUS, more short-term EUS programs have been conducted across Asia in recent years. In this aspect, the Asian EUS Group (AEG) has taken the lead to fast-track the dissemination of EUS knowledge and skills across Asia through its multinational network of training centers. AEG's programs are brought to wherever there is demand. Its versatile modular structure allows the program to be easily customized and scaled up or down to align to local needs, making it highly adaptable to the changing and varying needs in different countries. Even with the current pandemic situation, it has been able to continue its training efforts through the use of technology, including webinars, and live case demonstration.

Endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal polyps: A meta-analysis and meta-regression with single arm analysis.

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.

Multinational survey on the preferred approach to management of Barrett's esophagus in the Asia-Pacific region.

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.

Two Magnetic Sensor Based Real-Time Tracking of Magnetically Inflated Swallowable Intragastric Balloon.

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.

Artificial intelligence in upper GI endoscopy - current status, challenges and future promise.

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.