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.

Malaysian Society of Gastroenterology and Hepatology consensus statement on metabolic dysfunction-associated fatty liver disease.

The Malaysian Society of Gastroenterology and Hepatology saw the need for a consensus statement on metabolic dysfunction-associated fatty liver disease (MAFLD). The consensus panel consisted of experts in the field of gastroenterology/hepatology, endocrinology, bariatric surgery, family medicine, and public health. A modified Delphi process was used to prepare the consensus statements. The panel recognized the high and increasing prevalence of the disease and the consequent anticipated increase in liver-related complications and mortality. Cardiovascular disease is the leading cause of mortality in MAFLD patients; therefore, cardiovascular disease risk assessment and management is important. A simple and clear liver assessment and referral pathway was agreed upon, so that patients with more severe MAFLD can be linked to gastroenterology/hepatology care, while patients with less severe MAFLD can remain in primary care or endocrinology, where they are best managed. Lifestyle intervention is the cornerstone in the management of MAFLD. The panel provided a consensus on the use of statin, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, sodium-glucose cotransporter-2 inhibitor, glucagon-like peptide-1 agonist, pioglitazone, vitamin E, and metformin, as well as recommendations on bariatric surgery, screening for gastroesophageal varices and hepatocellular carcinoma, and liver transplantation in MAFLD patients. Increasing the awareness and knowledge of the various stakeholders on MAFLD and incorporating MAFLD into existing noncommunicable disease-related programs and activities are important steps to tackle the disease. These consensus statements will serve as a guide on MAFLD for clinicians and other stakeholders.

Epidemiological trends of gastrointestinal and liver diseases in Malaysia: A single-center observational study.

BACKGROUND AND AIM: The spectrum of gastrointestinal (GI) and liver diseases is recognized to have a geographical variation, which may be due to environmental or genetic differences. We aimed to explore this further in a specialist clinic serving a multi-ethnic Asian urban population. METHODS: A retrospective analysis of outpatient data from this institution's electronic medical records was conducted between January and June 2019. Clinical diagnoses of GI and liver diseases and associated demographic information were collected. RESULTS: Data from 3676 adult patients (median age 62 years, female 51.1%) were available for analysis. The frequency of luminal GI, liver and pancreato-biliary diseases were 34.2%, 63.2%, and 2.6%, respectively. Among luminal GI diseases, 38.6% were functional gastrointestinal disorders and 61.4% had an organic cause. A higher proportion of patients of Indian ethnicity were diagnosed with IBD compared with other ethnic groups (India 21.9%, Malay 16.5%, Chinese 12.2%, P = 0.001). Among liver diseases, the most common etiologies were HBV (44.4%) and NAFLD (39.3%). Cirrhosis and/or hepatocellular carcinoma were present in 18% of liver diseases, with NAFLD as the most frequent etiology. Among patients with NAFLD, a higher proportion of ethnic Malays and Indians were evident (Malay 53.8% vs Chinese 28.7% vs Indian 61.1%, P < 0.001). In contrast, a greater proportion of ethnic Chinese were diagnosed with HBV compared with other ethnic groups (Malay 30.9% vs Chinese 57.5% vs Indian 8.4%, P < 0.001). CONCLUSION: The spectrum of GI and liver diseases has a peculiar epidemiology, particularly with reference to the ethnic predilection of certain diseases.

Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis.

OBJECTIVE: To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO). DESIGN: In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs). RESULTS: In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively. CONCLUSION: Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms. TRIAL REGISTRATION NUMBER: NCT02388724.

Practice of endoscopy during COVID-19 pandemic: position statements of the Asian Pacific Society for Digestive Endoscopy (APSDE-COVID statements).

Coronavirus-19 (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Risk of transmission may occur during endoscopy and the goal is to prevent infection among healthcare professionals while providing essential services to patients. Asia was the first continent to have a COVID-19 outbreak, and this position statement of the Asian Pacific Society for Digestive Endoscopy shares our successful experience in maintaining safe and high-quality endoscopy practice at a time when resources are limited. Sixteen experts from key societies of digestive endoscopy in Asia were invited to develop position statements, including patient triage and risk assessment before endoscopy, resource prioritisation and allocation, regular monitoring of personal protective equipment, infection control measures, protective device training and implementation of a strategy for stepwise resumption of endoscopy services after control of the COVID-19 outbreak.

Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus.

OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Searching for an optimal therapy for H pylori eradication: High-dose proton-pump inhibitor dual therapy with amoxicillin vs. standard triple therapy for 14 days.

BACKGROUND & AIMS: We compared a high-dose dual therapy (HDDT) with rabeprazole and amoxicillin and compared it with a standard triple therapy (STT) with rabeprazole, amoxicillin, and clarithromycin for 2 weeks for H pylori eradication in treatment naïve patients. METHODS: H pylori-positive patients were randomly assigned to either a rabeparzole (Pariet) 20 mg b.i.d., amoxicillin (Ospamox) 1 g b.i.d. and clarithromycin (Klacid) 500 mg b.i.d. for 14 days or rabeprazole (Pariet) 20 mg q.i.d., amoxicillin (Ospamox) 1 g q.i.d. also for 14 days. Eradication was tested for by the C13 -UBT at least 4 weeks after the completion of therapy. RESULTS: H pylori was eradicated in 86.2% of patients (81/94) (95% CI: 77.8-91.7) in the STT group compared with 92.8% (90/97) (95% CI: 85.9-96.5) in the HDDT group on ITT analysis. On PP analysis, H pylori was eradicated in 91.0% of patients (81/89) (95% CI: 83.3-95.4) in the STT group compared with 93.8% (90/96) (95% CI: 87.0-97.1) in the HDDT group. Side effects were few although many patients in the STT arm complained of bitter taste. The HDDT arm was well tolerated by patients. CONCLUSIONS: The HDDT gave a high eradication rate comparable to the STT for 2 weeks and was a well-tolerated regimen for H pylori eradication.

Predictors of advanced fibrosis in elderly patients with biopsy-confirmed nonalcoholic fatty liver disease: the GOASIA study.

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 < 0.001). By multivariable analysis, factors associated with advanced fibrosis in elderly patients included female sex [odds ratio (OR) 3.21; 95% confidence interval (CI) 1.37-7.54] and hypertension (OR 3.68; 95%CI 1.11-12.23). The area under receiver-operating characteristics curve (95% CI) of aspartate aminotransferase-to-platelet ratio index, NAFLD fibrosis score and Fibrosis-4 index for predicting advanced fibrosis in elderly patients were 0.62 (0.52-0.72), 0.65 (0.55-0.75) and 0.64 (0.54-0.74) respectively. 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.

Optimizing Use of Nonalcoholic Fatty Liver Disease Fibrosis Score, Fibrosis-4 Score, and Liver Stiffness Measurement to Identify Patients With Advanced Fibrosis.

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.

Polymorphisms in the host CYP2C19 gene and antibiotic-resistance attributes of Helicobacter pylori isolates influence the outcome of triple therapy.

Objectives: Eradication of Helicobacter pylori is influenced by susceptibility to antimicrobial agents, elevated bacterial load and degree of acid inhibition, which can be affected by genotypes of drug-metabolizing enzymes [cytochrome P450 (CYP) 2C19 polymorphism]. Theoretically, the choice and dose of proton pump inhibitor may also influence the suppression of H. pylori infection. The CYP2C19 genotype has recently been found to have an impact on peptic ulcer healing, H. pylori eradication and therapeutic efficacy of proton pump inhibitors. Methods: Here, we investigated the impact of the CYP2C19 genotype polymorphism and the success of triple therapy (fluoroquinolones/metronidazole/clarithromycin) on antibiotic-resistant strains in eradicating H. pylori in human subjects with non-ulcer dyspepsia (NUD), in human subjects with peptic ulcer disease (PUD) and in asymptomatic human subjects (positive and negative for H. pylori infection). Results: Based on the CYP2C19 genotypes, determined by Droplet Digital PCR (ddPCR) analysis, we found 11.2%, 62.5% and 26.3% corresponding to rapid metabolizers, intermediate metabolizers and poor metabolizers, respectively. However, we did not find any significant effect for homozygous ABCB1 or CYP2C19*2 and CYP2C19*3 alleles. We detected several participants heterozygous for both ABCB1 and CYP2C19*2, CYP2C19*3 and CYP2C19*17 loci. The participants heterozygous for both ABCB1 and CYP2C19*2 and *3 loci should be defined as intermediate and poor metabolizers according to the haplotype analysis in the NUD, PUD and asymptomatic subjects. Conclusions: Consequently, fluoroquinolones/metronidazole/clarithromycin-based triple therapies can be used to eradicate H. pylori infection, if one does not know the CYP2C19 genotype of the patient.

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia.

The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.

Bleeding detection in wireless capsule endoscopy videos - Color versus texture features.

Wireless capsule endoscopy (WCE) is an effective technology that can be used to make a gastrointestinal (GI) tract diagnosis of various lesions and abnormalities. Due to a long time required to pass through the GI tract, the resulting WCE data stream contains a large number of frames which leads to a tedious job for clinical experts to perform a visual check of each and every frame of a complete patient's video footage. In this paper, an automated technique for bleeding detection based on color and texture features is proposed. The approach combines the color information which is an essential feature for initial detection of frame with bleeding. Additionally, it uses the texture which plays an important role to extract more information from the lesion captured in the frames and allows the system to distinguish finely between borderline cases. The detection algorithm utilizes machine-learning-based classification methods, and it can efficiently distinguish between bleeding and nonbleeding frames and perform pixel-level segmentation of bleeding areas in WCE frames. The performed experimental studies demonstrate the performance of the proposed bleeding detection method in terms of detection accuracy, where we are at least as good as the state-of-the-art approaches. In this research, we have conducted a broad comparison of a number of different state-of-the-art features and classification methods that allows building an efficient and flexible WCE video processing system.

The 2017 M Balasegaram Memorial Lecture: The Changing Landscape of Liver Diseases in Malaysia-60 Years On!

The landscape of liver diseases in Malaysia has changed dramatically since the time of Professor Balasegaram Manickavasagar-an eminent surgeon in the 1960s. The most significant discoveries in hepatology have been that of hepatitis B virus in 1963 and hepatitis C virus in 1989, which have both been shown to be predominantly blood borne diseases. Hepatitis B and C infections result in long term carrier state and a high propensity to develop liver cirrhosis and cancer. Hepatitis B is the most common cause of liver cirrhosis and cancer in Malaysia. Blood bank screening and public health preventive measures have reduced the disease burden significantly and an effective vaccination for hepatitis B is now incorporated in our National Immunisation Programme. Although no vaccine is available for hepatitis C, highly effective eradication therapies were introduced in 2011. These agents will significantly change the disease scenario across the world. A "new" disease was described in 1980, by Ludwig et al.-non-alcoholic fatty liver (NAFLD) disease. With the global epidemic of obesity and diabetes mellitus, NAFLD is set to increase exponentially across the world including in Malaysia. It will be the most important liver disease in the future, replacing hepatitis B and C infections.

Management of patients on antithrombotic agents undergoing emergency and elective endoscopy: joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines.

This Guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society for Digestive Endoscopy (APSDE). It was developed in response to the increasing use of antithrombotic agents (antiplatelet agents and anticoagulants) in patients undergoing gastrointestinal (GI) endoscopy in Asia. After reviewing current practice guidelines in Europe and the USA, the joint committee identified unmet needs, noticed inconsistencies, raised doubts about certain recommendations and recognised significant discrepancies in clinical practice between different regions. We developed this joint official statement based on a systematic review of the literature, critical appraisal of existing guidelines and expert consensus using a two-stage modified Delphi process. This joint APAGE-APSDE Practice Guideline is intended to be an educational tool that assists clinicians in improving care for patients on antithrombotics who require emergency or elective GI endoscopy in the Asian Pacific region.

Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018.

Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.

Findings from a large Asian chronic hepatitis C real-life study.

There is a paucity of information on chronic hepatitis C (CHC) patients treated with direct antiviral agents (DAAs) in Asia. We invited Asia-Pacific physicians to collate databases of patients enrolled for CHC treatment, recording baseline clinical, virologic and biochemical characteristics, sustained virologic response at week 12 (SVR12) and virologic failure. SVR12 outcome was based on intention to treat (ITT). Multivariate analysis was used to assess independent risk factors for SVR12 using SPSS version 20. A total of 2171 patients from India (n = 977), Myanmar (n = 552), Pakistan (n = 406), Thailand (n = 139), Singapore (n = 72) and Malaysia (n = 25) were collected. At baseline, mean age was 49 years, 50.2% were males, and 41.8% had cirrhosis. Overall, SVR12 was 89.5% and by genotype (GT) based on ITT and treatment completion, respectively, was 91% and 92% for GT1, 100% and 100% for GT2, 91% and 97% for GT3, 64% and 95% for GT4, 87% and 87% for GT6 and 79% and 91% for GT untested. Patients with cirrhosis had SVR12 of 85% vs 93% for noncirrhosis (P < 0.001) (RR 2.1, 95% CI 1.4-3.1, P = 0.0002). Patients with GT1 and GT3 treated with sofosbuvir/ribavirin (SR) had 88% and 89% SVR12, respectively, but those GT6 treated with sofosbuvir/ledipasvir (SL) had only 77.6% SVR12. Multivariate analysis showed absence of cirrhosis was associated with higher SVR12 (OR 2.0, 95% CI 1.3-3.1, P = 0.002). In conclusion, patients with GT1 and GT3 with/without cirrhosis had surprisingly high efficacy using SR, suggesting that Asians may respond better to some DAAs. However, poor GT6 response to SL suggests this regimen is suboptimal for this genotype.

Helicobacter pylori outer inflammatory protein A (OipA) suppresses apoptosis of AGS gastric cells in vitro.

Outer inflammatory protein A (OipA) is an important virulence factor associated with gastric cancer and ulcer development; however, the results have not been well established and turned out to be controversial. This study aims to elucidate the role of OipA in Helicobacter pylori infection using clinical strains harbouring oipA "on" and "off" motifs. Proteomics analysis was performed on AGS cell pre-infection and postinfection with H. pylori oipA "on" and "off" strains, using liquid chromatography/mass spectrometry. AGS apoptosis and cell cycle assays were performed. Moreover, expression of vacuolating cytotoxin A (VacA) was screened using Western blotting. AGS proteins that have been suggested previously to play a role or associated with gastric disease were down-regulated postinfection with oipA "off" strains comparing to oipA "on" strains. Furthermore, oipA "off" and ΔoipA cause higher level of AGS cells apoptosis and G0/G1 cell-cycle arrest than oipA "on" strains. Interestingly, deletion of oipA increased bacterial VacA production. The capability of H. pylori to induce apoptosis and suppress expression of proteins having roles in human disease in the absence of oipA suggests that strains not expressing OipA may be less virulent or may even be protective against carcinogenesis compared those expressing OipA. This potentially explains the higher incidence of gastric cancer in East Asia where oipA "on" strains predominates.

The impact of wire caliber on ERCP outcomes: a multicenter randomized controlled trial of 0.025-inch and 0.035-inch guidewires.

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

Development of Image-enhanced Endoscopy of the Gastrointestinal Tract: A Review of History and Current Evidences.

Endoscopy imaging of the gastrointestinal (GI) tract has evolved tremendously over the last few decades. Key milestones in the development of endoscopy imaging include the use of various dyes for chromoendoscopy, the application of optical magnification in endoscopy, the introduction of high-definition image capturing and display technology and the application of altered illuminating light to achieve vascular and surface enhancement. Aims of this review paper are to summarize the development and evolution of modern endoscopy imaging and in particular, imaged-enhanced endoscopy (IEE), to promote appropriate usage, and to guide future development of good endoscopy practice. A search of PubMed database was performed to identify articles related to IEE of the GI tract. Where appropriate, landmark trials and high-quality meta-analyses and systematic reviews were used in the discussion. In this review, the developments and evolutions in endoscopy imaging and in particular, IEE, were summarized into discernible eras and the literature evidence with regard to the strengths and weaknesses in term of their detection and characterization capability in each of these eras were discussed. It is in the authors' opinion that IEE is capable of fairly good detection and accurate characterization of various GI lesions but such benefits may not be readily reaped by those who are new in the field of luminal endoscopy. Exposure and training in making confident diagnoses using these endoscopy imaging technologies are required in tandem with these new developments in order to fully embrace and adopt the benefits.