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BackgroundThere were limited data on the risk of post-polypectomy bleeding (PPB) in patients on direct oral anticoagulants (DOAC). We aimed to evaluate the PPB and thromboembolic risks among DOAC and warfarin users in a population-based cohort.MethodsWe performed a territory-wide retrospective cohort study involving patients in Hong Kong from 2012 to 2020. Patients who received an oral anticoagulant and had undergone colonoscopy with polypectomy were identified. Propensity-score models with inverse probability of treatment weighting were developed for the warfarin-DOAC and between-DOAC comparisons. The primary outcome was clinically significant delayed PPB, defined as repeat colonoscopy requiring haemostasis within 30 days. The secondary outcomes were 30-day blood transfusion requirement and new thromboembolic event.ResultsApixaban was associated with lower PPB risk than warfarin (adjusted HR (aHR) 0.39, 95% CI 0.24 to 0.63, pFor thromboembolic events, apixaban was associated with lower risk than warfarin (aHR 0.22, 95% CI 0.11 to 0.45, pConclusionsApixaban was associated with a significantly lower risk of PPB and thromboembolism than warfarin, dabigatran and rivaroxaban, particularly in older patients with right-sided polyps.

Artificial intelligence (AI)-assisted colonoscopy improves polyp detection and characterization in colonoscopy. However, data from large-scale multicenter randomized controlled trials (RCT) in an asymptomatic population are lacking.This multicenter RCT aimed to compare AI-assisted colonoscopy with conventional colonoscopy for adenoma detection in an asymptomatic population. Asymptomatic subjects 45-75 years of age undergoing colorectal cancer screening by direct colonoscopy or fecal immunochemical test were recruited in 6 referral centers in Hong Kong, Jilin, Inner Mongolia, Xiamen, and Beijing. In the AI-assisted colonoscopy, an AI polyp detection system (Eagle-Eye) with real-time notification on the same monitor of the endoscopy system was used. The primary outcome was overall adenoma detection rate (ADR). Secondary outcomes were mean number of adenomas per colonoscopy, ADR according to endoscopist's experience, and colonoscopy withdrawal time. This study received Institutional Review Board approval (CRE-2019.393).From November 2019 to August 2021, 3059 subjects were randomized to AI-assisted colonoscopy (n = 1519) and conventional colonoscopy (n = 1540). Baseline characteristics and bowel preparation quality between the 2 groups were similar. The overall ADR (39.9% vs 32.4%; P.001), advanced ADR (6.6% vs 4.9%; P = .041), ADR of expert (42.3% vs 32.8%; P.001) and nonexpert endoscopists (37.5% vs 32.1%; P = .023), and adenomas per colonoscopy (0.59 ± 0.97 vs 0.45 ± 0.81; P.001) were all significantly higher in the AI-assisted colonoscopy. The median withdrawal time (8.3 minutes vs 7.8 minutes; P = .004) was slightly longer in the AI-assisted colonoscopy group.In this multicenter RCT in asymptomatic patients, AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists. (ClinicalTrials.gov, Number: NCT04422548).

Faecal microbiota transplantation (FMT) has been used extensively in the treatment of various gastrointestinal and extra-intestinal conditions, despite that there are still a lot of missing gaps in our knowledge in the gut microbiota and its behaviour. This article describes the unknowns in microbiota biology (undetected microbes, uncertain colonization, unclear mechanisms of action, uncertain indications, unsure long-term efficacy, or side effects). We discuss how these unknowns may affect the therapeutic uses of FMT, and the potentials and caveats of other related microbiota-based therapies. When used as an experimental therapy or last resort in difficult conditions, caution should be taken against inadvertent complications. Clear documentations of post-treatment events should be made mandatory, classified and graded as in clinical trials. Further robust scientific experiments and properly designed clinical studies are needed.

Colorectal cancer (CRC) is a common cancer globally. It is a complex disease influenced by genetic and environmental factors. Early studies on familial cases have identified major genes involved in CRC, such as proto-oncogenes KRAS, PIK3CA and BRAF, and tumour-suppressor genes APC and TP53. These genes have provided valuable insight into the molecular pathogenesis of CRC, and some have made ways to clinical utility to help diagnose cancer syndromes, prognosticate oncological outcomes and predict treatment responses. While these genetic factors are important, recent studies have suggested contribution of microorganisms to colorectal carcinogenesis. Observational studies, animal experiments and translational works have identified several microorganisms as potential carcinogenic bacteria, such as Fusobacterium nucleatum and Peptostreptococcus anaerobius. With the advent of sequencing technology and bioinformatics, more genomic and metagenomic factors are being uncovered as important players in CRC carcinogenesis. This article aims to review recent genomic and metagenomic discoveries relating to CRC.

ObjectiveThere is a need for early detection of colorectal cancer (CRC) at precancerous-stage adenoma. Here, we identified novel faecal bacterial markers for diagnosing adenoma.DesignThis study included 1012 subjects (274 CRC, 353 adenoma and 385 controls) from two independent Asian groups. Candidate markers were identified by metagenomics and validated by targeted quantitative PCR.ResultsMetagenomic analysis identified ‘m3’ from a Lachnoclostridium sp., Fusobacterium nucleatum (Fn) and Clostridium hathewayi (Ch) to be significantly enriched in adenoma. Faecal m3 and Fn were significantly increased from normal to adenoma to CRC (pm3 may perform better than Fn in distinguishing adenoma from controls (areas under the receiver operating characteristic curve (AUROCs) m3=0.675 vs Fn=0.620, p=0.09), while Fn performed better in diagnosing CRC (AUROCs Fn=0.862 vs m3=0.741, pm3 and Fn showed sensitivities of 48.3% and 33.8% for adenoma, and 62.1% and 77.8% for CRC, respectively. In a subgroup tested with faecal immunochemical test (FIT; n=642), m3 performed better than FIT in detecting adenoma (sensitivities for non-advanced and advanced adenomas of 44.2% and 50.8% by m3 (specificity=79.6%) vs 0% and 16.1% by FIT (specificity=98.5%)). Combining with FIT improved sensitivity of m3 for advanced adenoma to 56.8%. The combination of m3 with Fn, Ch, Bacteroides clarus and FIT performed best for diagnosing CRC (specificity=81.2% and sensitivity=93.8%).ConclusionThis study identifies a novel bacterial marker m3 for the non-invasive diagnosis of colorectal adenoma.

Background and aim Comorbid generalized anxiety disorder and irritable bowel syndrome are common and therapeutically challenging. We aimed to assess the effectiveness of electroacupuncture in relieving anxiety and bowel symptoms in Chinese adults with this form of comorbidity. Methods In a single-blind randomized sham-controlled trial, subjects with comorbid generalized anxiety disorder and irritable bowel syndrome were randomly assigned to receive 10 weekly sessions of electroacupuncture or sham electroacupuncture. Patients were assessed at baseline, immediately after intervention and at 6-week follow-up. Primary outcome was anxiety (7-item Patient Health Questionnaire section for anxiety). Secondary outcomes included bowel symptoms (bowel symptoms questionnaire), depressive symptoms (9-item Patient Health Questionnaire), somatic symptoms (15-item Patient Health Questionnaire), and health-related quality of life (EuroQol-5 Dimensions). Results Eighty subjects, 40 in each arm, were randomized. All but two in the sham group completed 10 weekly sessions. There was no significant difference in the proportion of patients experiencing significant (≥ 50%) reduction of anxiety symptoms between the two groups immediately after intervention (32.4% vs 21.6%, P = 0.06) and at 6-week follow-up (25.7% in electroacupuncture vs 27% in sham, P = 0.65). Anxiety, depressive symptom, and bowel symptom severity did not differ significantly between electroacupuncture and sham groups. Conclusions Findings failed to support the effectiveness of electroacupuncture for comorbid generalized anxiety disorder and irritable bowel syndrome. Further studies are needed to identify effective acupuncture treatment protocols for such comorbidity.

BACKGROUND Faecal microbiota transplantation (FMT) is effective for Clostridium difficile infections (CDI) refractory to standard treatment and is being studied in other diseases. AIM To evaluate donor characteristics, procedures and clinical outcomes of FMT. METHODS We systematically reviewed FMT studies published up to 29 August 2018 using MEDLINE (R) and EMBASE and identified clinical studies with FMT donor information. We reported data on donor characteristics, screening criteria, administration, clinical outcomes and adverse events. RESULTS Among 5267 reports, 239 full-text articles were screened and 168 articles were included. FMT was performed commonly for CDI (n = 108) and inflammatory bowel disease (IBD) (n = 31). We reported characteristics of 1513 donors [58% male; mean age, 34.3 years; mean body mass index, 21.6]. Donors in Asia were younger than the West (mean age 30.7 vs 32.9, P = 0.00075). Less than 50% of studies screened donors for transmittable pathogens. Final cure rate for CDI was 95.6% (95% confidence interval [CI], 93.9%-97.1%) and final remission rates for ulcerative colitis (UC) and Crohn's disease (CD) were 39.6% (95% CI, 25.4%-54.6%) and 47.5% (95% CI, 29.4%-65.8%), respectively. Cure rates in CDI and final remission rates for CD and UC were comparable across all routes of FMT administration. Overall adverse event incidence was

Evidence of prophylactic clipping is inconsistent except for proximal and large colonic lesions in the general population. Although warfarin and direct oral anticoagulants (DOACs) are significant risk factors of postpolypectomy bleeding (PPB), dedicated studies to examine the benefit of prophylactic clipping in these high-risk patients remain limited.We performed a propensity score-weighted retrospective cohort study from 2012 to 2020. Patients who received an oral anticoagulant and underwent colonoscopic polypectomy were included. Data were collected on baseline demographics, medications (anticoagulant, antiplatelet, and heparin bridging), and endoscopies (polyp number, location, size, morphology, histopathology, resection method and prophylactic clipping). Propensity-score models with inverse probability of treatment weighting were developed between prophylactic clipping and no clipping groups. Unbalanced variables were included in a doubly robust model with multivariate analysis. The primary outcome was clinically significant delayed PPB, defined as a composite endpoint of hemoglobin drop ≥2 g/dL, blood transfusion, or repeat colonoscopy for hemostasis within 30 days.Five hundred forty-seven patients with 1485 polyps were included. Prophylactic clipping was not associated with a reduced risk of PPB (odds ratio [OR], 1.19; 95% confidence interval [CI], .73-1.95; P = .497). The hot resection method was associated with a significantly higher risk of PPB (OR, 9.76; 95% CI, 3.94-32.60; P .001) compared with cold biopsy or snare polypectomy. In a subgroup analysis, prophylactic clipping was associated with a lower PPB risk in patients on DOACs (OR, .36; 95% CI, .16-.82; P = .015).Prophylactic clipping was not associated with an overall reduced risk of PPB in patients on oral anticoagulants. The use of cold snare polypectomy should be maximized in anticoagulated patients.

Background and aim: Gastrointestinal manifestations of the coronavirus disease 2019 (COVID-19) pandemic may mimic irritable bowel syndrome (IBS), and social distancing measures may affect IBS patients negatively. We aimed to study the impact of COVID-19 on respondents with self-reported IBS. Methods: We conducted an anonymized survey from May to June 2020 in 33 countries. Knowledge, attitudes, and practices on personal hygiene and social distancing as well as psychological impact of COVID-19 were assessed. Statistical analysis was performed to determine differences in well-being and compliance to social distancing measures between respondents with and without self-reported IBS. Factors associated with improvement or worsening of IBS symptoms were evaluated. Results: Out of 2704 respondents, 2024 (74.9%) did not have IBS, 305 (11.3%) had self-reported IBS, and 374 (13.8%) did not know what IBS was. Self-reported IBS respondents reported significantly worse emotional, social, and psychological well-being compared with non-IBS respondents and were less compliant to social distancing measures (28.2% vs 35.3%, P = 0.029); 61.6% reported no change, 26.6% reported improvement, and 11.8% reported worsening IBS symptoms. Higher proportion of respondents with no change in IBS symptoms were willing to practice social distancing indefinitely versus those who deteriorated (74.9% vs 51.4%, P = 0.016). In multivariate analysis, willingness to continue social distancing for another 2-3 weeks (vs longer period) was significantly associated with higher odds of worsening IBS. Conclusion: Our study showed that self-reported IBS respondents had worse well-being and compliance to social distancing measures than non-IBS respondents. Future research will focus on occupational stress and dietary changes during COVID-19 that may influence IBS.

Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, causing significant mortality. There is a mechanistic relationship between intracellular coronavirus replication and deregulated autophagosome–lysosome system. We performed transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and identified the aberrant upregulation of genes in the lysosome pathway. We further determined the capability of two circulating markers, namely microtubule-associated proteins 1A/1B light chain 3B (LC3B) and (p62/SQSTM1) p62, both of which depend on lysosome for degradation, in predicting the emergence of moderate-to-severe disease in COVID-19 patients requiring hospitalization for supplemental oxygen therapy. Logistic regression analyses showed that LC3B was associated with moderate-to-severe COVID-19, independent of age, sex and clinical risk score. A decrease in LC3B concentration

Colorectal cancer (CRC) is a heterogeneous disease with different gene expression patterns. There are two major colorectal carcinogenesis pathways: conventional adenoma-carcinoma pathway and alternative serrated neoplasia pathway. Apart from the conventional pathway that is typically initiated by characteristic APC mutation and chromosomal instability, the serrated neoplasia pathway is mainly characterized by mutations of BRAF or KRAS, microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). Despite the malignant potential of serrated lesions, they can be easily overlooked during endoscopy screening and even in pathological assessment due to its anatomical location, morphology, and histological features. It has been shown that environmental factors especially the gut microbial composition play a key role in CRC pathogenesis. Thus, the preferential localization of serrated lesions in specific intestine areas suggest that niche-specific microbiota composition might intertwined with host genetic perturbations during the development of serrated lesions. Although serrated lesions and conventional adenomas are biologically different, most studies have focused on conventional adenomas, while the pathophysiology and role of microorganisms in the development of serrated lesions remain elusive. In this review, we discuss on the role of gut microbiota in the serrated neoplasia pathway of colorectal carcinogenesis and its specific clinical and molecular features, and summarize the potential mechanisms involved.

ObjectiveThe impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).DesignIn this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24.ResultsProportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (pBifidobacterium and Lactobacillus compared with FMT alone (pConclusionRepeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients’ microbiota and improvement in lipid profile and liver stiffness.Trial registration numberNCT03127696.

Background The Coronavirus Disease 2019 (COVID-19) pandemic had a huge impact on healthcare systems globally. Decline in hospital admissions for common medical emergencies was observed. We investigated its collateral effect on hospitalizations and clinical outcomes in patients with gastrointestinal (GI) and liver diseases in Hong Kong. Methods We performed a territory-wide retrospective cohort study in Hong Kong from January 1, 2019, to May 31, 2020. Data were retrieved through Clinical Data Analysis and Reporting System. We included patients admitted to hospitals with top diagnoses of luminal GI cancers, pancreatico-hepatobiliary cancers, benign pancreaticobiliary disorders, liver diseases, non-infective enteritis and colitis, non-variceal and variceal upper gastrointestinal bleeding (UGIB). We excluded patient-based hospital admissions without emergency department attendance and length of stay equal to or shorter than one day. The primary endpoint was the total number of index hospital admissions related to these diagnoses at different time points. The secondary endpoints were in-hospital mortality, intensive care unit admission, elective or emergency operations and endoscopy. The COVID-19 period was defined as the time after the first local case in January 2020, week 4. Results We recorded a total of 195,867 hospital admissions related to GI diseases during the study period, and 125,049 of them were included in the final analysis. Comparing the same pre-COVID19 and COVID-19 periods, we observed a significant decline in the average number of hospitalizations for GI diseases (17.0% reduction, P Conclusions The number of hospitalizations related to GI diseases reduced drastically during the COVID-19 epidemic, yet no excessive in-hospital mortality was observed. More emergency endoscopies and operations were required, particularly for UGIB and benign pancreaticobiliary conditions.

Background and Aim We have previously shown that fecal microbial markers might be useful for non‐invasive diagnosis of colorectal cancer (CRC) and adenoma. Here, we assessed the application of microbial DNA markers, as compared with and in combination with fecal immunochemical test (FIT), in detecting CRC and adenoma in symptomatic patients and asymptomatic subjects. Methods We recruited 676 subjects [210 CRC, 115 advanced adenoma (AA), 86 non‐advanced adenoma, and 265 non‐neoplastic controls], including 241 symptomatic and 435 asymptomatic subjects. Fecal abundances of Fusobacterium nucleatum, a Lachnoclostridium sp. m3, Bacteroides clarus, and Clostridium hathewayi were quantified by quantitative PCR. Combining score of the four microbial markers (4Bac) and diagnostic prediction were determined using our previously established scoring model and cutoff values and FIT with a cutoff of 100 ng Hb/mL. Results 4Bac detected similar percentages of CRC [85.3% (95%CI: 79.2–90.2%) vs 84.9% (68.1–94.9%)] and AA [35.7% (12.8–64.9%) vs 38.6% (29.1–48.8%)], while FIT detected more CRC [72.1% (63.7–79.4%) vs 66.7% (48.2–82.0%)] and AA [28.6% (8.4–58.1%) vs 16.8% (10.1–25.6%)], in symptomatic vs asymptomatic subjects, respectively. Focusing on the asymptomatic cohort, 4Bac was more sensitive for diagnosing CRC and AA than FIT (P

Background & Aims Proteus spp, Gram-negative facultative anaerobic bacilli, have recently been associated with Crohn's disease (CD) recurrence after intestinal resection. We investigated the genomic and functional role of Proteus as a gut pathogen in CD. Methods Proteus spp abundance was assessed by ure gene–specific polymerase chain in 54 pairs of fecal samples and 101 intestinal biopsies from patients with CD and healthy controls. The adherence, invasion, and intracellular presence of 2 distinct isolates of Proteus mirabilis in epithelial cells were evaluated using immunofluorescence and electron microscopy. Intracellular gene expression profiles and regulated pathways were analyzed by RNA sequencing and KEGG pathway analysis. Biologic functions of 2 isolates of P mirabilis were determined by in vitro cell culture, and in vivo using conventional mice and germ-free mice. Results Proteus spp were significantly more prevalent and abundant in fecal samples and colonic tissue of patients with CD than controls. A greater abundance of the genus Fusobacterium and a lesser abundance of the genus Faecalibacterium were seen in patients with CD with a high Proteus spp abundance. All 24 Proteus monoclones isolated from patients with CD belonged to members of P mirabilis lineages and 2 isolates, recovered from stool or mucosa, were used in further studies. Mice gavaged with either P mirabilis strain had more severe colonic inflammation. Co-culture of the isolates with epithelial cell lines showed bacterial adherence, invasion, increased production of pro-inflammatory cytokines IL-18 and IL-1α, and cell necrosis. Both isolates induced key pro-inflammatory pathways, including NOD-like receptor signaling, Jak-STAT signaling, and MAPK signaling, and induced pro-inflammatory genes and activated inflammation-related pathways in gnotobiotic mice. Conclusions P mirabilis in the gut is associated with CD and can induce inflammation in cells and animal models of colitis. P mirabilis can act as a pathobiont and play a crucial role in the pathogenesis of CD.

Irritable bowel syndrome (IBS) is a chronic disease prevalent in today’s society and diet remains the most common aggravator of IBS symptoms. Existing literature suggest that IBS patients are dysbiotic as evidence indicates decreased levels of Bifidobacteria, Bacteroidetes and Faecalibacterium prausnitzii and increased levels of Firmicutes in comparison to healthy individuals. Studies suggest that changes in diet can modulate gut microbiota and therefore improve IBS symptoms. The two diets being investigated are the low FODMAP diet and the use of probiotics. A low FODMAP diet implements a reduction in the amount of poorly absorbed carbohydrates and probiotics are live microorganisms that have been proven beneficial when consumed appropriately. Based on the literature acquired from PubMed, a positive correlation appears to exist between the low FODMAP diet and IBS symptoms; 57% report symptom relief. There is also a notable effect on the gut microbiome after changing to low FODMAP diet, noted with a significant decrease in levels of Bifidobacterium, Clostridium, F. prausnitzii and Actinobacteria. This poses a concern as bacteria such as Bifidobacteria and F. prausnitzii are beneficial for health. When probiotics are taken amongst IBS patients a reduction in symptoms is also observed. Additionally, there is an increase in the abundance of Bifidobacterium and Lactobacilli. It is suggested that co-administration of probiotics with a low FODMAP diet may ensure beneficial levels of Bifidobacterium while IBS symptoms ameliorate.

From its beginning in December 2019, the coronavirus disease 2019 outbreak has spread globally from Wuhan and is now declared a pandemic by the World Health Organization. The sheer scale and severity of this pandemic is unprecedented in the modern era. Although primarily a respiratory tract infection transmitted by direct contact and droplets, during aerosol-generating procedures, there is a possibility of airborne transmission. In addition, emerging evidence suggests possible fecal-oral spread of the virus. Clinical departments that perform endoscopy are faced with daunting challenges during this pandemic. To date, multiple position statements and guidelines have been issued by various professional organizations to recommend practices in endoscopic procedures. This article aims to summarize and discuss available evidence for these practices, to provide guidance for endoscopy to enhance patient safety, avoid nosocomial outbreaks, protect healthcare personnel, and ensure rational use of personal protective equipment. Responses adapted to national recommendations and local infection control guidelines and tailored to the availability of medical resources are imminently needed to fight the coronavirus disease 2019 pandemic.

The novel coronavirus disease is currently causing a major pandemic. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the Betacoronavirus genus that also includes the SARS-CoV and Middle East respiratory syndrome coronavirus. While patients typically present with fever and a respiratory illness, some patients also report gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Studies have identified the SARS-CoV-2 RNA in stool specimens of infected patients, and its viral receptor angiotensin converting enzyme 2 was found to be highly expressed in gastrointestinal epithelial cells. These suggest that SARS-CoV-2 can actively infect and replicate in the gastrointestinal tract. This has important implications to the disease management, transmission, and infection control. In this article, we review the important gastrointestinal aspects of the disease.

Changes in the intestinal microbiota have been associated with development and progression of colorectal cancer (CRC). Archaea are stable components of the microbiota, but little is known about their composition or contribution to colorectal carcinogenesis. We analyzed archaea in fecal microbiomes of 2 large cohorts of patients with CRC.We performed shotgun metagenomic analyses of fecal samples from 585 participants (184 patients with CRC, 197 patients with adenomas, and 204 healthy individuals) from discovery (165 individuals) and validation (420 individuals) cohorts. Assignment of taxonomies was performed by exact k-mer alignment against an integrated microbial reference genome database.Principal component analysis of archaeomes showed distinct clusters in fecal samples from patients with CRC, patients with adenomas, and control individuals (P.001), indicating an alteration in the composition of enteric archaea during tumorigenesis. Fecal samples from patients with CRC had significant enrichment of halophilic and depletion of methanogenic archaea. The halophilic Natrinema sp. J7-2 increased progressively in samples from control individuals, to patients with adenomas, to patients with CRC. Abundances of 9 archaea species that were enriched in fecal samples from patients with CRC distinguished them from control individuals with areas under the receiver operating characteristic curve of 0.82 in the discovery cohort and 0.83 in the validation cohort. An association between archaea and bacteria diversities was observed in fecal samples from control individuals but not from patients with CRC. Archaea that were enriched in fecal samples from patients with CRC had an extensive mutual association with bacteria that were enriched in the same samples and exclusivity with bacteria that were lost from these samples.Archaeomes of fecal samples from patients with CRC are characterized by enrichment of halophiles and depletion of methanogens. Studies are needed to determine whether associations between specific archaea and bacteria species in samples from patients with CRC contribute to or are a response to colorectal tumorigenesis.

ObjectivesBacteriome and virome alterations are associated with colorectal cancer (CRC). Nevertheless, the gut fungal microbiota in CRC remains largely unexplored. We aimed to characterise enteric mycobiome in CRC.DesignFaecal shotgun metagenomic sequences of 184 patients with CRC, 197 patients with adenoma and 204 control subjects from Hong Kong were analysed (discovery cohort: 73 patients with CRC and 92 control subjects; validation cohort: 111 patients with CRC, 197 patients with adenoma and 112 controls from Hong Kong). CRC-associated fungal markers and ecological changes were also validated in additional independent cohorts of 90 patients with CRC, 42 patients with adenoma and 66 control subjects of published repository sequences from Germany and France. Assignment of taxonomies was performed by exact k-mer alignment against an integrated microbial reference genome database.ResultsPrincipal component analysis revealed separate clusters for CRC and control (pConclusionsThis study revealed CRC-associated mycobiome dysbiosis characterised by altered fungal composition and ecology, signifying that the gut mycobiome might play a role in CRC.

ObjectiveWhile it is recommended that patients presenting with acute upper gastrointestinal bleeding (AUGIB) should receive endoscopic intervention within 24 hours, the optimal timing is still uncertain. We aimed to assess whether endoscopy timing postadmission would affect outcomes.DesignWe conducted a retrospective, territory-wide, cohort study with healthcare data from all public hospitals in Hong Kong. Adult patients (age ≥18) that presented with AUGIB between 2013 and 2019 and received therapeutic endoscopy within 48 hours (n=6474) were recruited. Patients were classified based on endoscopic timing postadmission: urgent (t≤6), early (6ResultsResults showed that urgent timing (n=1008) had worse outcomes compared with early endoscopy (n=3865), with higher 30-day all-cause mortality (pConclusionCompared with urgent and late endoscopy among patients who have received therapeutic endoscopies, early endoscopy was associated with superior outcomes especially among patients with non-variceal bleeding. This supports the notion that non-variceal AUGIB patients should receive endoscopy within 24 hours, but also emphasises the importance of prior resuscitation and pharmacotherapy.

Advances in research techniques have made it possible to map the microbial communities in the gastrointestinal (GI) tract, where the majority of bacteria in the human body reside. Disturbances in these communities are referred to as dysbiosis and have been associated with GI cancers. Although dysbiosis is observed in several GI malignancies, the specific role of these changes has not been understood to the extent of Helicobacter pylori (HP) in gastric cancer (GC). This review will address the bacterial communities along the GI tract, from the oral cavity to the anal canal, particularly focusing on bacterial dysbiosis and carcinogenesis. Just as non-HP bacteria in the stomach may interact with HP in gastric carcinogenesis, the same may hold true for other GI tract malignancies, where an interplay between microbes in carcinogenesis seems conceivable, especially in colorectal cancer (CRC). In the last part of this review we will discuss the potential mechanisms of bacterial dysbiosis in GI carcinogenesis.

Background and Aims Endoscopic and histological healing are associated with improved clinical outcomes in ulcerative colitis [UC]. We aimed to investigate the predictive value of faecal immunochemical test [FIT] for endoscopic and histological healing in UC. Methods We measured quantitative FIT and faecal calprotectin [FC] in 140 consecutive UC patients who underwent colonoscopy. We assessed the diagnostic accuracy of FIT for predicting endoscopic healing using the Mayo endoscopic subscore [MES 0/1] and for histological healing using the Geboes score [< 2.0] and Nancy index [grade ≤ 1]. The predictive abilities of FIT were compared with those of FC. Results FIT had an area under the curve [AUC] of 0.77 (95% confidence interval [CI] 0.67-0.86, p < 0.001) for endoscopic healing, an AUC of 0.77 [95% CI 0.67-0.86, p < 0.001] using the Geboes score, and 0.77 [95% CI 0.66-0.85, p < 0.001] using the Nancy Index for histological healing. The AUC of FIT was comparable to that of FC for endoscopic healing [p = 0.773] and histological healing [p = 0.767-0.960], and was comparable to colonoscopy for histological healing [p = 0.384-0.673]. FIT < 50 ng/ml predicted endoscopic healing with a sensitivity, specificity, and positive predictive value [PPV] of 72%, 68%, and 82%, respectively, and for histological healing with a sensitivity, specificity, and PPV of 73-75%, 67%, and 78-80%, respectively. Combining FIT with FC led to a higher specificity [90%] for histological healing. Over 85% of patients with FIT < 50 ng/ml and FC < 50 μg/g achieved histological healing. Conclusions FIT is highly sensitive and accurate to predict endoscopic and histological healing in UC. It represents a promising non-invasive tool for monitoring mucosal healing in UC.

BACKGROUND AND AIM Colorectal cancer (CRC) incidence is rising among

Background Biological therapies, thiopurines and steroid are commonly used in the treatment of inflammatory bowel disease (IBD) and may cause hepatitis B virus (HBV) reactivation. However, their exact risk of hepatitis B flare in patients with previous HBV exposure is poorly defined. We aim to study the risk of hepatitis flare in IBD patients with previous HBV exposure. Methods Patients were identified from a territory-wide Hong Kong IBD Registry. IBD patients who were negative for HBsAg and received biological therapies or thiopurines or steroids from 1 January 2000 to 30 June 2019 were included. Patients who were positive for total antibody to hepatitis B core antigen (anti-HBc) and/or hepatitis B surface antigen (anti-HBs) were defined to have previous HBV exposure. Primary endpoint was development of hepatitis flare (alanine Aminotransferase [ALT) >80U/L). Results Total 369 patients fulfilled the inclusion criteria and were classified into three groups: anti-HBs positive only (n = 246); anti-HBs and anti-HBc positive (n = 78) and anti-HBc positive only (n = 45). Median follow-up duration was 60 months (Interquartile range: 32.7–60 months). Seventy-six IBD patients (20.6%) developed hepatitis flare. Cumulative incidence of hepatitis flare were 13.2%, 18.3% and 22% at 12 months, 36 months and 60 months respectively. Use of thiopurine [adjusted hazard ratio (aHR) 2.56; 95% Confidence Interval (CI) 1.54 – 4.26, p < 0.001]and ever exposure to steroid [aHR 2.73; 95% CI 1.30–5.72; p = 0.008] were risk factors for hepatitis flare after adjustment of baseline ALT level. The use of biological therapy was not associated with risk of hepatitis flare [aHR 1.79; 95% CI 0.79–3.99; p = 0.14]. Ever exposure to steroid was associated with increased risk of hepatitis flare irrespective of the peak dose (40mg daily) [aHR: 2.34–4.18]. Fifteen patients (4.1%) developed severe icteric hepatitis flare (ALT > 120U/L and bilirubin >38 mmol/L). Cumulative incidence of severe icteric hepatitis flare were 2.7%, 7.2% and 8.4% at 12 months, 36 months and 60 months respectively. Conclusion Amongst IBD patients with previous HBV exposure who were treated with biological therapy, thiopurines or steroid, 20.6% developed hepatitis flare. The use of thiopurine and ever exposure to steroid were risk factors for hepatitis flare. The use of biological therapy was not associated with risk of hepatitis flare.

Objective Patients with resolved hepatitis B virus (HBV) infection are at risk of HBV reactivation during treatment for hematological malignancies. We conducted a systematic review and meta-analysis of the data on the efficacy of antiviral prophylaxis for the prevention of HBV reactivation in this group of patients. Methods We conducted a systemic literature search of PubMed including MEDLINE and EMBASE databases to 31 January 2019 to identify studies published in English comparing antiviral prophylaxis with no prophylaxis for HBV reactivation in patients treated for hematological malignancies. The search terms used were ("occult hepatitis B" OR "resolved hepatitis B") AND ("reactivation") AND ("haematological malignancy" OR "hematological malignancy" OR "chemotherapy" OR "immunotherapy" OR "chemoimmunotherapy" OR "lymphoma" OR "leukemia" OR "transplant"). The primary outcome was the reactivation of HBV infection. Pooled estimates of relative risk (RR) were calculated. Results We identified 13 relevant studies including two randomized controlled trials (RCT), one post hoc analysis from RCT and 10 cohort studies. There was a trend towards a lower rate of HBV reactivation using antiviral prophylaxis, but the difference was not significant (RR 0.57, 95% confidence interval [CI] 0.23-1.40, P = 0.22). When limiting the analysis to the three prospective studies of patients receiving anti-CD20 monoclonal antibodies, we found antiviral prophylaxis was associated with a significantly lower risk of HBV reactivation (RR 0.17, 95% CI 0.06-0.49, P = 0.001). Conclusion Antiviral prophylaxis reduced the risk of HBV reactivation in patients receiving anti-CD20 monoclonal antibodies for hematological malignancies but not in a broader group of patients receiving anticancer therapy.

Colorectal cancer (CRC) accounts for about 10% of all new cancer cases globally. Located at close proximity to the colorectal epithelium, the gut microbiota comprises a large population of microorganisms that interact with host cells to regulate many physiological processes, such as energy harvest, metabolism and immune response. Sequencing studies have revealed microbial compositional and ecological changes in patients with CRC, whereas functional studies in animal models have pinpointed the roles of several bacteria in colorectal carcinogenesis, including Fusobacterium nucleatum and certain strains of Escherichia coli and Bacteroides fragilis. These findings give new opportunities to take advantage of our knowledge on the gut microbiota for clinical applications, such as gut microbiota analysis as screening, prognostic or predictive biomarkers, or modulating microorganisms to prevent cancer, augment therapies and reduce adverse effects of treatment. This Review aims to provide an overview and discussion of the gut microbiota in colorectal neoplasia, including relevant mechanisms in microbiota-related carcinogenesis, the potential of utilizing the microbiota as CRC biomarkers, and the prospect for modulating the microbiota for CRC prevention or treatment. These scientific findings will pave the way to clinically translate the use of gut microbiota for CRC in the near future.

Background It is unknown whether cognitive dysfunction found in patients with irritable bowel syndrome (IBS) was attributable to the different subtypes, ongoing pathophysiological processes, trait characteristics, or psychiatric comorbidity. Methods Forty Rome-III patients with IBS (20 diarrhea-predominant [IBS-D] and 20 constipation-predominant [IBS-C]) and 40 age-, sex-, education-matched healthy controls were systematically recruited and compared on their cognitive function with continuous performance test (CPT), Wisconsin Card Sorting Test (WCST) and emotional Stroop test. Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Patient Health Questionnaire-15 (PHQ-15) and a structured bowel symptom questionnaire were performed to measure anxiety, depressive, somatization, and bowel symptoms, respectively. Psychiatric diagnoses were ascertained with SCID-I (Structured Clinical Interview for DSM-IV Axis I Disorders). Key results Patients with IBS showed significantly increased standard deviation of reaction time (SDRT) (P = .003) on CPT, increased failure to maintain set (FMS) (P=.002), and percentage of perseverative errors (P = .003) on WCST. SDRT did not correlate with illness chronicity or bowel symptoms. FMS correlated with bowel symptom severity. In logistic regression models controlled for BAI, BDI-II, and PHQ-15, SDRT (AOR = 1.08, P = .025), but not FMS (P = .25) or percentage of perseverative errors (P = .24), significantly differentiated IBS from controls. Cognitive function was not significantly different between IBS-C and IBS-D (P > .05), or between pure IBS (n = 22) and IBS with generalized anxiety disorder (GAD) (n = 17) (P > .05). Conclusions & inferences Patients with IBS showed attentional and executive function impairment irrespective of subtypes but otherwise heterogeneous in terms of its state-trait correlations and overlap with anxiety comorbidity.

Background & Aims Streptococcus thermophilus was identified to be depleted in patients with colorectal cancer (CRC) by shotgun metagenomic sequencing of 526 multicohort fecal samples. Here, we aim to investigate whether this bacterium could act as a prophylactic for CRC prevention. Methods The antitumor effects of S thermophilus were assessed in cultured colonic epithelial cells and in 2 murine models of intestinal tumorigenesis. The tumor-suppressive protein produced by S thermophilus was identified by mass spectrometry and followed by β-galactosidase activity assay. The mutant strain of S thermophilus was constructed by homologous recombination. The effect of S thermophilus on the gut microbiota composition was assessed by shotgun metagenomic sequencing. Results Oral gavage of S thermophilus significantly reduced tumor formation in both Apcmin/+ and azoxymethane-injected mice. Coincubation with S thermophilus or its conditioned medium decreased the proliferation of cultured CRC cells. β-Galactosidase was identified as the critical protein produced by S thermophilus by mass spectrometry screening and β-galactosidase activity assay. β-Galactosidase secreted by S thermophilus inhibited cell proliferation, lowered colony formation, induced cell cycle arrest, and promoted apoptosis of cultured CRC cells and retarded the growth of CRC xenograft. The mutant S thermophilus without functional β-galactosidase lost its tumor-suppressive effect. Also, S thermophilus increased the gut abundance of known probiotics, including Bifidobacterium and Lactobacillus via β-galactosidase. β-Galactosidase-dependent production of galactose interfered with energy homeostasis to activate oxidative phosphorylation and downregulate the Hippo pathway kinases, which partially mediated the anticancer effects of S thermophilus. Conclusion S thermophilus is a novel prophylactic for CRC prevention in mice. The tumor-suppressive effect of S thermophilus is mediated at least by the secretion of β-galactosidase.

Objective There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma. Design We measured relative abundance of Fusobacterium nucleatum ( Fn ), Peptostreptococcus anaerobius ( Pa ) and Parvimonas micra ( Pm ) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects. Results The abundance was higher for all three individual markers in patients with CRC than controls (p Fn in patients with advanced adenoma than controls (p=0.022). The marker Fn , when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p Conclusions This study identified marker Fn as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.

Background: The incidence of Crohn’s disease (CD) is increasing in Asia and Eastern Europe. Limited studies have reported on the frequency of upper gastrointestinal (GI) involvement in patients with CD in non-Western countries. This prospective study compared the rate of macroscopic and microscopic upper GI manifestations and Helicobacter pylori (H. pylori) positivity in asymptomatic CD patients in Asia and Eastern Europe. Methods: Consecutive asymptomatic CD patients were prospectively recruited for upper GI endoscopy between 2013 and 2015 in Hong Kong and in Hungary. Endoscopy and biopsy findings were recorded and histology was performed to assess for H. pylori and microscopic signs characteristic for CD, using standardized diagnostic criteria. Results: One hundred and eighty CD patients (100 Hong Kong; 80 Hungary; 70.6% male; mean age, 38.5 years) and 189 controls (100 Hong Kong; 89 Hungary; 57.7% male; mean age 41 years) were included. Gastroduodenal involvement of CD was significantly higher in Hungary than in Hong Kong (16.5% vs 2.0%, p≤0.001). H. pylori positivity was significantly higher in Hungarian than Chinese CD patients (13.9% vs. 4.0%, p≤0.001). Granulomas were detected in 1% in Hong Kong and 7.6% in Hungary (p≤0.001). Chinese CD subjects had a significantly lower H. pylori positivity compared with controls (6% vs. 15%; p≤0.001). Conclusion: Upper GI CD was significantly higher in Eastern Europe compared with Asia. The detection of granuloma in Hungary was similar to the literature data, whereas focal gastritis was lower than expected in both cohorts.

Inflammatory bowel disease (IBD) has become more common in Asia over the past few decades. The rate of increase in prevalence of the disease varies greatly in Asia, with several countries in East Asia experiencing a more than doubled increase in IBD prevalence over the past decade. Historically, ulcerative colitis (UC) is more common than Crohn's disease (CD) in Asia. However, a reverse trend is beginning to appear in more developed countries in Asia such as Japan, Korea, and Hong Kong. While Asian IBD patients share many similarities with their Western counterparts, there are important differences with significant clinical implications. In Asia, there are more men with CD, more ileo-colonic involvement in CD, less familial aggregation, fewer extra-intestinal manifestations and worse clinical outcomes for older-onset patients with UC. These differences are likely related to the different genetic makeup and environmental exposures in different regions. Evaluation of the differences and rates in epidemiologic trends may help researchers and clinicians estimate disease burden and understand the reasons behind these differences, which may hold the key to unravel the etiology of IBD.

SummaryBackground The performance of faecal occult blood tests (FOBTs) to screen proximally located colorectal cancer (CRC) has produced inconsistent results. Aim To assess in a meta-analysis, the diagnostic accuracy of FOBTs for relative detection of CRC according to anatomical location of CRC. Methods Diagnostic studies including both symptomatic and asymptomatic cohorts assessing performance of FOBTs for CRC were searched from MEDINE and EMBASE. Primary outcome was accuracy of FOBTs according to the anatomical location of CRC. Bivariate random-effects model was used. Subgroup analyses were performed to evaluate test performance of guaiac-based FOBT (gFOBT) and immunochemical-based FOBT (iFOBT). Results Thirteen studies, with 17 cohorts, reporting performance of FOBT were included; a total of 26 342 patients (mean age 58.9 years; 58.1% male) underwent both colonoscopy and FOBT. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of FOBTs for CRC detection in the proximal colon were 71.2% (95% CI 61.3–79.4%), 93.6% (95% CI 90.7–95.7%), 11.1 (95% CI 7.8–15.8) and 0.3 (95% CI 0.2–0.4) respectively. Corresponding findings for CRC detection in distal colon were 80.1% (95% CI 70.9–87.0%), 93.6% (95% CI 90.7–95.7%), 12.6 (95% CI 8.8–18.1) and 0.2 (95% CI 0.1–0.3). The area-under-curve for FOBT detection for proximal and distal CRC were 90% vs. 94% (P = 0.0143). Both gFOBT and iFOBT showed significantly lower sensitivity but comparable specificity for the detection of proximally located CRC compared with distal CRC. Conclusion Faecal occult blood tests, both guaiac- and immunochemical-based, show better diagnostic performance for the relative detection of colorectal cancer in the distal colon than in the proximal bowel.