Joint Asian Pacific Association of Gastroenterology (APAGE)-Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia.

Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.

Development of the global inflammatory bowel disease visualization of epidemiology studies in the 21st century (GIVES-21).

BACKGROUND: There is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development. METHODS: Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn's disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis. RESULTS: Through November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting. CONCLUSIONS: The GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries.

The impact of diet and ethnicity on gut microbiota variation in irritable bowel syndrome: A multi-center study.

BACKGROUND AND AIM: The gut microbiota in irritable bowel syndrome (IBS) is known to vary with diet. We aim to (i) analyze the gut microbiota composition of IBS patients from a multi-ethnic population and (ii) explore the impact of a low FODMAP diet on gastrointestinal symptoms and gut microbiota composition among IBS patients. METHODS: A multi-center study of multi-ethnic Asian patients with IBS was conducted in two phases: (i) an initial cross-sectional gut microbiota composition study of IBS patients and healthy controls, followed by (ii) a single-arm 6-week dietary interventional study of the IBS patients alone, exploring clinical and gut microbiota changes. RESULTS: A total of 34 adult IBS patients (IBS sub-types of IBS-D 44.1%, IBS-C 32.4%, and IBS-M 23.5%) and 15 healthy controls were recruited. A greater abundance of Parabacteroides species with lower levels of bacterial fermenters and short-chain fatty acids producers were found among IBS patients compared with healthy controls. Age and ethnicity were found to be associated with gut microbiota composition. Following a low FODMAP dietary intervention, symptom and quality of life improvement were observed in 24 (70.6%) IBS patients. Symptom improvement was associated with adherence to the low FODMAP diet (46.7% poor adherence vs 92.9% good adherence, P = 0.014), and gut microbiota patterns, particularly with a greater abundance of Bifidobacterium longum, Anaerotignum propionicum, and Blautia species post-intervention. CONCLUSION: Gut microbiota variation in multi-ethnic IBS patients may be related to dietary intake and may be helpful to identify patients who are likely to respond to a low FODMAP diet.

Dietary Risk Factors and Odds of Colorectal Adenoma in Malaysia: A Case Control Study.

Current evidence suggests that dietary and lifestyle factors may play an important role in colorectal cancer risk but there are only a few studies that investigated their relationship with colorectal adenomas (CRA), the precursors for colorectal cancer. A case-control study was conducted to determine the relationship between dietary and lifestyle factors associated with CRA risk among 125 subjects with CRA and 150 subjects without CRA at Hospital Canselor Tuanku Muhriz UKM (HCTM), Malaysia. We used dietary history questionnaire (DHQ) and International Physical Activity Questionnaire-Short Form (IPAQ) to estimate the diet and physical activity. The findings of this study showed that male gender [OR = 2.71 (95% CI= 1.01-7.27)], smoking [OR = 6.39 (95% CI= 1.04-39.30)], family history of cancer [OR = 6.39 (95% CI= 1.04-39.30)], high body fat percentage [OR = 1.25 (95% CI= 1.04-1.51)], high calorie and fat intake [OR = 1.03 (95% CI= 1.01-1.06)], [OR = 1.01 (95% CI= 0.95-1.09)] and red meat intake more than 100 g per day [OR = 1.02 (95% CI= 1.01-1.04)] increased CRA risk. High fiber [OR = 0.78 (95% CI= 0.64-0.95)] and calcium intake [OR = 0.78 (95% CI= 0.98-1.00)] was found to decrease CRA risk. Some of these modifiable risk factors could be advocated as lifestyle interventions to reduce risk of CRA.

Review of recent evidence on the management of heartburn in pregnant and breastfeeding women.

Gastroesophageal reflux disease (GERD) is one the most common medical complaints in pregnant women. Some women continue to experience GERD symptoms after delivery. Effective management of GERD symptoms is important to improve productivity and quality of life. Management of heartburn in pregnant and breastfeeding women involves lifestyle modifications, dietary modifications, non-pharmaceutical remedies and pharmaceutical drugs. For most patients, lifestyle/dietary modifications are helpful in reducing GERD symptoms. For patients who require a more intense intervention, various types of pharmaceutical drugs are available. However, the suitability of each treatment for use during pregnancy and lactation must be taken into consideration. This article explores the reported efficacy and safety of these treatment options in pregnant and breastfeeding women. Recommended treatment algorithm in pregnant and breastfeeding women have been developed.

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.

Current Updates on the Role of Microbiome in Endometriosis: A Narrative Review.

Endometriosis affects approximately 6 to 10% of reproductive-age women globally. Despite much effort invested, the pathogenesis that promotes the development, as well as the progression of this chronic inflammatory disease, is poorly understood. The imbalance in the microbiome or dysbiosis has been implicated in a variety of human diseases, especially the gut microbiome. In the case of endometriosis, emerging evidence suggests that there may be urogenital-gastrointestinal crosstalk that leads to the development of endometriosis. Researchers may now exploit important information from microbiome studies to design endometriosis treatment strategies and disease biomarkers with the use of advanced molecular technologies and increased computational capacity. Future studies into the functional profile of the microbiome would greatly assist in the development of microbiome-based therapies to alleviate endometriosis symptoms and improve the quality of life of women suffering from endometriosis.

A Malaysian consensus report on the diagnosis and treatment of Helicobacter pylori infection.

Helicobacter pylori is one of the most common chronic bacterial infections in humans and responsible for 90% of duodenal ulcers and 70-90% of gastric ulcers. Despite this, many misconceptions regarding the appropriate diagnostic method and treatment strategies still exist in the Malaysian clinical practice. Under the initiative of the steering committee, an expert panel consisting of nine key opinion leaders in the field of gastroenterology convened to develop a set of consensus statements that are relevant to the Malaysian healthcare practice. The panel members reviewed the current evidence on the management of H. pylori infection, focusing on the best practices that are relevant to the Malaysian population based on clinical experience and published clinical evidence. Using the modified Delphi method, the panel achieved consensus in three areas of H. pylori infection management: indications for testing, diagnosis, and treatment. The panel proposed a set of 19 consensus statements, which were synthesized via two rounds of blinded voting and group discussions. The recommendations provided are relevant to the Malaysian population and can be used as a guide by physicians across various healthcare settings to facilitate appropriate diagnostic testing and treatment of H. pylori infection.

An evaluation of dietary adequacy among patients with constipation-predominant irritable bowel syndrome in Malaysia.

BACKGROUND/AIMS: Substantial proportions of patients with constipation-predominant irritable bowel syndrome (IBS-C) linked their symptoms with particular intake of foods. However, there is lack of current data regarding the intake among IBS-C patients before any dietary interventions. Thus, this study aimed to evaluate the dietary adequacy among IBS-C against the standard recommended nutrient intake (RNI) and healthy controls. METHODS: A retrospective case-control study was conducted involving IBS-C patients and healthy control subjects. A validated 126-food items frequency questionnaire was administered to all the subjects to assess their dietary intake, guided by dietitians. The calculated nutrients intake for IBS-C patients was then compared against the standard RNI and healthy controls. RESULTS: A total of 306 subjects were recruited, among which 218 were diagnosed with IBS-C and 88 were included as healthy controls. IBS-C patients had significantly lower intake of wholegrain products, fried foods, dairy products, fruits, and vegetables compared to healthy controls. The daily intake of energy, certain macronutrients, and micronutrients among IBS-C patients was significantly lower than the healthy subjects. Less than 5% of IBS-C patients and healthy subjects achieved the standard recommendation for dietary fiber. Also, various vitamin intake (B1, B2, B6, folate, B12, E, K, and potassium) among IBS-C patients did not meet the standard RNI. CONCLUSIONS: Dietary intakes of IBS-C patients did not meet the recommended intake for Malaysian and showed the nutritional inadequacies compared to the control subjects. Our study highlighted the importance of dietary evaluation prior to planning strategies for dietary intervention targeting IBS-C patients.

The global burden of coeliac disease: opportunities and challenges.

Coeliac disease is a systemic disorder characterized by immune-mediated enteropathy, which is caused by gluten ingestion in genetically susceptible individuals. The clinical presentation of coeliac disease is highly variable and ranges from malabsorption through solely extra-intestinal manifestations to asymptomatic. As a result, the majority of patients with coeliac disease remain undiagnosed, misdiagnosed or experience a substantial delay in diagnosis. Coeliac disease is diagnosed by a combination of serological findings of disease-related antibodies and histological evidence of villous abnormalities in duodenal biopsy samples. However, variability in histological grading and in the diagnostic performance of some commercially available serological tests remains unacceptably high and confirmatory assays are not readily available in many parts of the world. Currently, the only effective treatment for coeliac disease is a lifelong, strict, gluten-free diet. However, many barriers impede patients' adherence to this diet, including lack of widespread availability, high cost, cross-contamination and its overall restrictive nature. Routine follow-up is necessary to ensure adherence to a gluten-free diet but considerable variation is evident in follow-up protocols and the optimal disease management strategy is not clear. However, these challenges in the diagnosis and management of coeliac disease suggest opportunities for future research.

Clinical features, treatment, and survival of patients with colorectal cancer with or without inflammatory bowel disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) increases the risk of colorectal cancer (CRC), indicating that inflammation might alter tumor characteristics and potentially affect treatment and survival. Published data on this topic are inconclusive, so we conducted a population-based study in Ireland to address it. METHODS: We used the National Cancer Registry to collect data on all patients diagnosed with CRC in Ireland from 1994 to 2005 (n = 22,335) and identified those who also had IBD (n = 170). The clinical characteristics, treatment, and survival of patients with IBD and CRC were compared with those of patients with CRC without IBD. RESULTS: Patients with CRC and IBD were, on average, 7.7 years younger than those without IBD at diagnosis of CRC (P = .001), and were less likely to smoke (P = .002). Fewer CRCs in patients with IBD were stage 4 at diagnosis (12% vs 22% in non-IBD patients; P < .001). There was no significant difference in CRC treatment modalities between patients with or without IBD (P = .57). The median survival time of CRC patients with IBD was about 3 years longer than that of patients without IBD (P < .001). However, Cox proportional hazards analysis revealed that IBD was not a significant prognostic factor for CRC (P = .97). However, older age, male sex, smoking, and advanced grade and stage all were associated independently with shorter survival time. When propensity score matching was used to analyze outcomes, the survival times of CRC patients with and without IBD did not differ significantly. CONCLUSIONS: The features of patients with CRC and IBD differ significantly from those of CRC patients without IBD, but each group of patients receive similar treatment and have similar patterns of disease progression after diagnosis.

Biologics for the Management of Inflammatory Bowel Disease: A Review in Tuberculosis-Endemic Countries.

The advent of biologics and biologic therapy has transformed the management of inflammatory bowel disease (IBD) with enhanced early and adequate responses to treatment, fewer hospitalizations, a reduced need for surgery, and unprecedented outcomes including complete mucosal and histologic healing. However, an important issue with the use of anti-tumor necrosis factor (anti-TNF) agents in IBD is the increased risk of tuberculosis (TB). This is compounded by the diagnostic dilemma when differentiating between Crohn's disease and gastrointestinal TB, and the potentially serious consequences of initiating an incorrect treatment in the case of misdiagnosis. The interplay between IBD and TB is most relevant in Asia, where more than 60% of the 10.4 million new TB cases in 2016 were reported. A number of studies have reported an increased risk of TB with anti-TNF agents, including in patients who had tested negative for TB prior to treatment initiation. The limited evidence currently available regarding adhesion molecule antagonists such as vedolizumab suggests a comparatively lower risk of TB, thus making them a promising option for IBD management in TBendemic regions. This comprehensive review examines the available literature on the risk of TB with the use of biologics in the TB-endemic regions of Asia, focusing on the diagnostic dilemma, the risk of reactivation, and the optimized management algorithms for latent and active disease.

Multi-strain probiotics (Hexbio) containing MCP BCMC strains improved constipation and gut motility in Parkinson's disease: A randomised controlled trial.

OBJECTIVE: We determined the effectiveness of a multi-strain probiotic (Hexbio®) containing microbial cell preparation MCP®BCMC® on constipation symptoms and gut motility in PD patients with constipation. METHODS: PD patients with constipation (ROME III criteria) were randomized to receive a multi-strain probiotic (Lactobacillus sp and Bifidobacterium sp at 30 X 109 CFU) with fructo-oligosaccaride or placebo (fermented milk) twice daily for 8 weeks. Primary outcomes were changes in the presence of constipation symptoms using 9 items of Garrigues Questionnaire (GQ), which included an item on bowel opening frequency. Secondary outcomes were gut transit time (GTT), quality of life (PDQ39-SI), motor (MDS-UPDRS) and non-motor symptoms (NMSS). RESULTS: Of 55 recruited, 48 patients completed the study: 22 received probiotic and 26 received placebo. At 8 weeks, there was a significantly higher mean weekly BOF in the probiotic group compared to placebo [SD 4.18 (1.44) vs SD 2.81(1.06); (mean difference 1.37, 95% CI 0.68, 2.07, uncorrected p<0.001)]. Patients in the probiotic group reported five times higher odds (odds ratio = 5.48, 95% CI 1.57, 19.12, uncorrected p = 0.008) for having higher BOF (< 3 to 3-5 to >5 times/week) compared to the placebo group. The GTT in the probiotic group [77.32 (SD55.35) hours] reduced significantly compared to placebo [113.54 (SD 61.54) hours]; mean difference -36.22, 95% CI -68.90, -3.54, uncorrected p = 0.030). The mean change in GTT was 58.04 (SD59.04) hour vs 20.73 (SD60.48) hours respectively (mean difference 37.32, 95% CI 4.00, 70.63, uncorrected p = 0.028). No between-groups differences were observed in the NMSS, PDQ39-SI, MDS-UPDRS II and MDS-UPDRS III scores. Four patients in the probiotics group experienced mild reversible side effects. CONCLUSION: This study showed that consumption of a multi-strain probiotic (Hexbio®) over 8 weeks improved bowel opening frequency and whole gut transit time in PD patients with constipation.

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 (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD 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 the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide 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 IBD 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.

Optimizing the multidimensional aspects of the patient-physician relationship in the management of inflammatory bowel disease.

The patient-physician relationship has a pivotal impact on the inflammatory bowel disease (IBD) outcomes. However, there are many challenges in the patient-physician relationship; lag time in diagnosis which results in frustration and an anchoring bias against the treating gastroenterologist, the widespread availability of medical information on the internet has resulted in patients having their own ideas of treatment, which may be incongruent from the treating physicians' goals resulting in patient physician discordance. Because IBD is an incurable disease, the goal of treatment is to sustain remission. To achieve this, patients may have to go through several lines of treatment. The period of receiving stepping up, top down or even accelerated stepping up medications may result in a lot of frustration and anxiety for the patient and may compromise the patient-physician relationship. IBD patients are also prone to psychological distress that further compromises the patient-physician relationship. Despite numerous published data regarding the medical and surgical treatment options available for IBD, there is a lack of data regarding methods to improve the therapeutic patient-physician relationship. In this review article, we aim to encapsulate the challenges faced in the patient-physician relationship and ways to overcome in for an improved outcome in IBD.

Post-transcriptional regulation of microRNAs in cancer: From prediction to validation.

MicroRNA (miRNA) is a small non-coding RNA with an established function to regulate genes at the post-transcriptional level leading to suppression or degradation of its messenger RNA expression (mRNA). Its dysregulation plays a vital role in a variety of biological and pathological processes including cancer. A lot of algorithms have been established to predict the target sites of miRNA, but experimentally identifying and validating its target region is still lacking. Guidance in experimental procedures is really needed to find genuine miRNA targets. Therefore, in this review, we provide an outline on the workflow in predicting and validating the targeted sites of miRNA using several methods as a guideline for the scientists. The final outcome of this type of experiment is essential to explore the major impact of miRNAmRNA interaction involved in the biological processes and to assist miRNA-based drug development in the future.

Gastroesophageal reflux disease in pregnancy.

Gastroesophageal reflux disease during pregnancy is common. Altered structure and function of the normal physiological barriers to reflux of gastric contents into the oesophagus explain the high incidence of this problem in pregnant women. For the majority of patients, life-style modifications are helpful, but are not sufficient to control symptoms and medication is required. The optimum management of reflux in pregnant patients requires special attention and expertise, since the safety of the mother, foetus and neonate remain the primary focus. Gastroenterologists and obstetricians should work together to optimise treatment. Typically, one utilises a step-up program that starts with life-style modifications and antacids. If those methods fail, histamine-2 receptor antagonists and proton pump inhibitors are tried. Rarely, promotility agents are used. Initiation of these medications must be undertaken after a careful discussion of risks and benefits with patients. In patients without a prior history of reflux, symptoms usually abate after delivery.