Showing papers in "BMJ Open Gastroenterology in 2019"

High potency multistrain probiotic improves liver histology in non-alcoholic fatty liver disease (NAFLD): a randomised, double-blind, proof of concept study

Abstract: Objective Pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still evolving. Probiotics could be a promising treatment option, but their effectiveness needs to be established. The present study aimed to evaluate the efficacy of a high potency multistrain probiotic in adult patients with NAFLD. Methods Thirty-nine liver biopsy-proven patients with NAFLD were randomised in a double-blind fashion to either lifestyle modifications plus an oral multistrain probiotic (675 billion bacteria daily, n=19) or identical placebo (n=20) for 1 year. Lifestyle modifications included regular exercise for all and control of overweight/obesity (with additional dietary restrictions), hypertension and hyperlipidaemia in those with these risk factors. Primary objective of the study was the histological improvement in NAFLD activity score (NAS) and its components and secondary objectives were improvement in alanine transaminase (ALT) and cytokine profile. Results Thirty (76.9%) out of 39 patients with NAFLD completed the study with 1 year of follow-up. A repeat liver biopsy at 1 year could be done in 10 patients (52.6%) in probiotic group and five patients (25%) in placebo group. In comparison to baseline, hepatocyte ballooning (p=0.036), lobular inflammation (p=0.003) and NAS score (p=0.007) improved significantly at 1 year in the probiotic group. When compared with placebo, the NAS score improved significantly in the probiotic group (p=0.004), along with improvements in hepatocyte ballooning (p=0.05) and hepatic fibrosis (p=0.018). A significant improvement in levels of ALT (p=0.046), leptin (p=0.006), tumour necrosis factor-α (p=0.016) and endotoxins (p=0.017) was observed in probiotic group in comparison to placebo at 1 year. No significant adverse events were reported in the study. Conclusion Patients with NAFLD managed with lifestyle modifications and multistrain probiotic showed significant improvement in liver histology, ALT and cytokines. Trial registration number The clinical trial is registered with CLINICAL TRIAL REGISTRYINDIA (CTRI); http://ctri.nic.in, No. CTRI/2008/091/000074

Impact of introducing a faecal immunochemical test (FIT) for haemoglobin into primary care on the outcome of patients with new bowel symptoms: a prospective cohort study

Abstract: Objective To determine whether a faecal immunochemical test (FIT) for faecal haemoglobin concentration (f-Hb) can be safely implemented in primary care as a rule-out test for significant bowel disease (SBD) (colorectal cancer (CRC), higher risk adenoma (HRA) and inflammatory bowel disease (IBD)) when used as an adjunct to the clinical assessment of new bowel symptoms. Design Single-centre prospective cohort study of all patients who attended primary care and submitted a FIT in the first calendar year of the service beginning December 2015. f-Hb was estimated using HM-JACKarc (Kyowa Medex) with a clinical cut-off of ≥10 µg Hb/g faeces. Incident cases of CRC were verified via anonymised record linkage to the Scottish Cancer Registry. Results 5422 patients submitted 5660 FIT specimens, of which 5372 were analysed (positivity: 21.9%). 2848 patients were referred immediately to secondary care and three with f-Hb Conclusion In primary care, measurement of f-Hb, in conjunction with clinical assessment, can safely and objectively determine a patient’s risk of SBD.

Alcohol and hepatocellular carcinoma

Abstract: Background Alcohol is classified as a Group 1 carcinogen by the International Agency for Research on Cancer because it induces hepatocellular carcinoma (among other cancers) in humans. An excessive alcohol intake may result in fatty liver, acute/chronic hepatitis, and cirrhosis and eventually lead to hepatocellular carcinoma. It has been reported that alcohol abuse increases the relative risk of hepatocellular carcinoma by 3- to 10-fold. Aim and Methods To clarify the known mechanisms of alcohol-related carcinogenesis, we searched Pubmed using the terms alcohol and immune mechanism, alcohol and cancer, and immune mechanism and cancer and summarized the articles as a qualitative review. Results From a clinical perspective, it is well known that alcohol interacts with other factors, such as smoking, viral hepatitis, and diabetes, leading to an increased risk of hepatocellular carcinoma. There are several possible mechanisms through which alcohol may induce liver carcinogenicity, including the mutagenic effects of acetaldehyde and the production of ROS due to the excessive hepatic deposition of iron. Furthermore, it has been reported that alcohol accelerates hepatitis C virus-induced liver tumorigenesis through TLR4 signaling. Despite intense investigations to elucidate the mechanisms, they remain poorly understood. Conclusion This review summarizes the recent findings of clinical and pathological studies that have investigated the carcinogenic effects of alcohol in the liver.

Gallstone ileus: a review.

Abstract: Background Gallstone ileus is an important complication of cholecystolithiasis. In general, surgery is the treatment of choice for such cases, but clinicians face difficulty in the selection of an appropriate approach. Closure of a cholecystoenteric fistula can be achieved through one-stage or two-stage operation. Two-stage operation has a lower mortality rate than a one-stage procedure, but persistence of the cholecystoenteric fistula is associated with the risk of carcinogenesis and recurrence of gallstone ileus. Objective This study reviews the different surgical approaches according to the impaction site of the gallstone, using data of previous studies by our group and clinical reports in the literature. Conclusions First, for cases involving impaction at the duodenum, the cholecystoenteric fistula can be repaired in the same surgical field, and one-stage operation obtains favourable outcome; hence, one-stage operation is considered as treatment of choice. Second, for cases involving impaction at the small intestine, natural closure of the cholecystoenteric fistula or low mortality is expected; hence, two-stage operation may be performed, possibly using minimally invasive laparoscopy. Third, for cases involving impaction at the colon, natural closure of the cholecystocolonic fistula is unlikely, and patients have a high risk of reflux cholangitis due to faecal fluid; hence, one-stage operation is considered as treatment of choice.

Combined effect of modifiable and non-modifiable risk factors for colorectal cancer risk in a pooled analysis of 11 population-based studies.

Abstract: Objective ‘Environmental’ factors associated with colorectal cancer (CRC) risk include modifiable and non-modifiable variables. Whether those with different non-modifiable baseline risks will benefit similarly from reducing their modifiable CRC risks remains unclear. Design Using 7945 cases and 8893 controls from 11 population-based studies, we combined 17 risk factors to characterise the overall environmental predisposition to CRC (environmental risk score (E-score)). We estimated the absolute risks (ARs) of CRC of 10 and 30 years across E-score using incidence-rate data from the Surveillance, Epidemiology, and End Results programme. We then combined the modifiable risk factors and estimated ARs across the modifiable risk score, stratified by non-modifiable risk profile based on genetic predisposition, family history and height. Results Higher E-score was associated with increased CRC risk (ORquartile, 1.33; 95% CI 1.30 to 1.37). Across E-scores, 30-year ARs of CRC increased from 2.5% in the lowest quartile (Q1) to 5.9% in the highest (Q4) quartile for men, and from 2.1% to 4.5% for women. The modifiable risk score had a stronger association in those with high non-modifiable risk (relative excess risk due to interaction=1.2, 95% CI 0.5 to 1.9). For those in Q4 of non-modifiable risk, a decrease in modifiable risk reduced 30-year ARs from 8.9% to 3.4% for men and from 6.0% to 3.2% for women, a level lower or comparable to the average population risk. Conclusions Changes in modifiable risk factors may result in a substantial decline in CRC risk in both sexes. Those with high inherited risk may reap greater benefit from lifestyle modifications. Our results suggested comprehensive evaluation of environmental factors may facilitate CRC risk stratification.

Risk factors for colorectal cancer significantly vary by anatomic site

Abstract: Objective To conduct an anatomic site-specific case–control study of candidate colorectal cancer (CRC) risk factors. Design Case–control study of US veterans with >1 colonoscopy during 1999–2011. Cases had cancer registry-identified CRC at colonoscopy, while controls were CRC free at colonoscopy and within 3 years of colonoscopy. Primary outcome was CRC, stratified by anatomic site: proximal, distal, or rectal. Candidate risk factors included age, sex, race/ethnicity, body mass index, height, diabetes, smoking status, and aspirin exposure summarised by adjusted ORs and 95% CIs. Results 21 744 CRC cases (n=7017 rectal; n=7039 distal; n=7688 proximal) and 612 646 controls were included. Males had significantly higher odds relative to females for rectal cancer (OR=2.84, 95% CI 2.25 to 3.58) than distal cancer (OR=1.84, 95% CI 1.50 to 2.24). Relative to whites, blacks had significantly lower rectal cancer odds (OR=0.88, 95% CI 0.82 to 0.95), but increased distal (OR=1.27, 95% CI 1.19 to 1.37) and proximal odds (OR=1.62, 95% CI 1.52 to 1.72). Diabetes prevalence was more strongly associated with proximal (OR=1.29, 95% CI 1.22 to 1.36) than distal (OR=1.15, 95% CI 1.08 to 1.22) or rectal cancer (OR=1.12, 95% CI 1.06 to 1.19). Current smoking was more strongly associated with rectal cancer (OR=1.81, 95% CI 1.68 to 1.95) than proximal cancer (OR=1.53, 95% CI 1.43 to 1.65) or distal cancer (OR=1.46, 95% CI 1.35 to 1.57) compared with never smoking. Aspirin use was significantly more strongly associated with reduced rectal cancer odds (OR=0.71, 95% CI 0.67 to 0.76) than distal (OR=0.85, 95% CI 0.81 to 0.90) or proximal (OR=0.91, 95% CI 0.86 to 0.95). Conclusion Candidate CRC risk factor associations vary significantly by anatomic site. Accounting for site may enable better insights into CRC pathogenesis and cancer control strategies.

Traditional serrated adenoma: an overview of pathology and emphasis on molecular pathogenesis

Abstract: Objective To provide an overview of the pathology and molecular pathogenesis of traditional serrated adenomas (TSA). Design Describe the morphology and molecules that play a role in their pathogenesis. Results These exuberant polypoid lesions are typified by tall cells with deeply eosinophilic cytoplasm, elongated nuclei bearing delicate chromatin, ectopic crypt foci, deep clefting of the lining mucosa and an overall resemblance to small bowel mucosa. Broadly, TSAs arise via three mechanisms. They may be BRAF mutated and CpG island methylator phenotype (CIMP)-high: right sided, mediated through a microvesicular hyperplastic polyp or a sessile serrated adenoma, may also have RNF43 mutations and result in microsatellite stable (MSS) colorectal cancers (CRC). The second pathway that is mutually exclusive of the first is mediated through KRAS mutation with CIMP-low TSAs. These are left-sided TSAs, are not associated with another serrated polyp and result in MSS CRC. These TSAs also have RSPO3, RNF43 and p53 mutations together with aberrant nuclear localisation of β-catenin. Third, there is a smaller group of TSAs that are BRAF and KRAS wild type and arise by as yet unknown molecular events. All TSAs show retention of mismatch repair proteins. Conclusion These are characteristic unusual polyps with a complex molecular landscape.

Gut microbiome identifies risk for colorectal polyps.

Abstract: Objective To characterise the gut microbiome in subjects with and without polyps and evaluate the potential of the microbiome as a non-invasive biomarker to screen for risk of colorectal cancer (CRC). Design Presurgery rectal swab, home collected stool, and sigmoid biopsy samples were obtained from 231 subjects undergoing screening or surveillance colonoscopy. 16S rRNA analysis was performed on 552 samples (231 rectal swab, 183 stool, 138 biopsy) and operational taxonomic units (OTU) were identified using UPARSE. Non-parametric statistical methods were used to identify OTUs that were significantly different between subjects with and without polyps. These informative OTUs were then used to build classifiers to predict the presence of polyps using advanced machine learning models. Results We obtained clinical data on 218 subjects (87 females, 131 males) of which 193 were White, 21 African-American, and 4 Asian-American. Colonoscopy detected polyps in 56% of subjects. Modelling of the non-invasive home stool samples resulted in a classification accuracy >75% for Naive Bayes and Neural Network models using informative OTUs. A naive holdout analysis performed on home stool samples resulted in an average false negative rate of 11.5% for the Naive Bayes and Neural Network models, which was reduced to 5% when the two models were combined. Conclusion Gut microbiome analysis combined with advanced machine learning represents a promising approach to screen patients for the presence of polyps, with the potential to optimise the use of colonoscopy, reduce morbidity and mortality associated with CRC, and reduce associated healthcare costs.

Use of ethylene-oxide gas sterilisation to terminate multidrug-resistant bacterial outbreaks linked to duodenoscopes.

Abstract: Background Cleaning and high-level disinfection have been the standard in the USA and other countries for reprocessing flexible endoscopes, including duodenoscopes and other types of gastrointestinal endoscopes. For decades, this practice has been a cornerstone for infection prevention in the endoscopic setting. However, amid recent reports associating the use of duodenoscopes with infections and outbreaks of carbapenem-resistant Enterobacteriaceae (CRE) and related multidrug-resistant organisms (MDROs), reasonable questions about the adequacy of current practices for reprocessing duodenoscopes have emerged. Objectives To review and evaluate the adequacy of current reprocessing practices for preventing duodenoscopes from transmitting CRE and related MDROs. Methods The MEDLINE/PubMed database was searched to identify published cases associating confirmed (or suspected) infections of CRE or a related MDRO with exposure to a duodenoscope since 2012, when duodenoscopes became a recognised risk factor for the transmission of CRE. The Internet was also searched to identify news articles and other reports documenting eligible cases occurring during this same timeframe but not identified during the MEDLINE database’s search. The Food and Drug Administration’s (FDA) medical device database was queried to identify regulatory reports describing these same types of cases, also recorded since 2012. The clinical and reprocessing details of each eligible case were reviewed to identify (when possible): (a) the reprocessing method (eg, high-level disinfection) performed at the time of the infections, (b) whether the facility’s compliance with the manufacturer’s reprocessing instructions was confirmed, and (c) the measure(s) or corrective action(s) the facility implemented to prevent additional multidrug-resistant infections. Results Seventeen cases in the USA and six in other countries (primarily Europe) associating infections (and colonizations) of CRE or a related MDRO with exposure to a duodenoscope were reviewed. Fourteen of these 23 outbreaks were caused by CRE, and six by a related MDRO. Two of these six latter cases identified Klebsiella pneumoniae carrying the mcr-1 gene as the pathogen. For 12 of these 23 cases, it was reported or implied that the duodenoscope was being high-level disinfected at the time of the infections, consistent with published guidelines. For the remaining 11 cases, the associated report(s) did not clearly identify how the duodenoscope was being reprocessed at the time of the infections (although it may be reasonably concluded that at least some, if not all, of these 11 cases involved high-level disinfection). Further, eight of the 23 cases reported the duodenoscope was being reprocessed in accordance with the manufacturer’s instructions for use (and professional guidelines) at the time of the infections. Seven of the cases discussed the design of the duodenoscope (eg, the forceps elevator mechanism) in the context of reprocessing and the infections. Three of the cases identified one or more reprocessing lapses, including inadequate cleaning, delayed reprocessing and improper drying and/or storage of the duodenoscope. Most of these 23 cases were associated with exposure to a duodenoscope model featuring a sealed elevator-wire channel. Six of the cases reported adopting (or in one case supplementing high-level disinfection with) ethylene oxide (EO) gas sterilisation of the duodenoscope, with at least three reporting this measure terminated the outbreak. Other measures adopted to prevent additional infections included removing the implicated duodenoscope from use, re-training staff about proper cleaning, microbiological culturing of the duodenoscope and returning the duodenoscope to the manufacturer for evaluation, maintenance and/or repair. Conclusions This study9s findings suggest current reprocessing practices may not always be sufficiently effective to prevent a duodenoscope from transmitting CRE and related MDROs, at least in some circumstances including an outbreak setting. Factors this review identified that may contribute to the device remaining contaminated after reprocessing include the device’s design; breaches of recommended reprocessing guidelines (eg, inadequate manual cleaning, delayed reprocessing or improper device storage); damage to the device; lacking servicing, maintenance or repair; and/or the presence of biofilms. Measures that can mitigate the impact of these and other reprocessing challenges and reduce, if not eliminate, the risk of transmission of CRE or a related MDRO by a duodenoscope include the use of EO gas sterilization (or another comparably effective process or method). In 2015, the FDA suggested healthcare facilities consider performing at least one of four supplemental measures, which include EO gas sterilisation, to improve the effectiveness of duodenoscope reprocessing. Whether the FDA and Centers for Disease Control and Prevention might reclassify duodenoscopes as critical devices requiring sterilisation is currently unresolved.

Moderately severe and severe acute pancreatitis : a systematic review of the outcomes in the USA and European Union-5.

Abstract: Background and objectives The global incidence of hospitalisation due to acute pancreatitis (AP) has been rising in the recent decades. In the USA alone, there was a 13.2% increase between 2009 and 2012 compared with 2002–2005. There remains a lack of approved treatments to prevent disease progression, leaving many liable to developing complications that include multisystem organ failure (OF) and death. This therapeutic deficit raises questions about the scale of the current burden of illness (BOI) associated with severe forms of AP. The aim of the systematic literature review (SLR) was to assess clinical, humanistic, and economic outcomes associated with moderately severe AP (MSAP) and severe AP (SAP) in the USA and the European Union-5 (EU-5). Methods Systematic searches were conducted in MEDLINE and Embase to identify studies published in English (between 2007 and 2017) that reported on the BOI of MSAP and/or SAP. Manual searches of ‘grey’ literature sources were also conducted. Results The SLR identified 19 studies which indicated that 15%–20% of patients with AP progress to more severe forms of the disease, up to 10.5% of those with SAP require surgery for complications, and up to 40% die during hospitalisation. By contrast, there appears to be a lack of data on the extent to which SAP affects patients’ quality of life. Conclusion The available evidence clearly demonstrates that the current management for MSAP and SAP in the USA and EU-5 does not adequately meet patients’ needs. Early identification and intervention for AP is crucial, given the evidence of high rates of morbidity and an associated economic burden that is considerable. Since many patients with the condition present to hospitals at a point when multisystem OF or death is highly likely, there is a particularly urgent need for effective treatment options to prevent disease progression.

Gastrointestinal lymphoma: The New mimic

Abstract: Background Gastrointestinal (GI) lymphomas comprise a group of distinct clinicopathological entities of B- or T- cell type, with primary gastrointestinal Hodgkin lymphoma being extremely uncommon. The GI tract is the predominant site of extranodal non-Hodgkin lymphoma accounting for 30–40% of all extranodal lymphomas. In the Western world, the stomach is the most commonly involved site followed by the small bowel. Several chronic inflammatory and immune-mediated disorders which predispose to accelerated cell turnover may lead to the malignant transformation of gut lymphocytes and ultimately manifest as GI lymphoma. The challenge for the clinical gastroenterologist is that these tumors may have varied presentations, ranging from nonspecific symptoms such as dyspepsia or bloating to abdominal pain, nausea, vomiting, GI bleeding, diarrhea, weight loss or bowel obstruction. Objective We illustrate the range of presentations of GI lymphoma with examples based on consecutive cases evaluated at our institution over a 6-month period. These cases demonstrate how appropriately directed endoscopic evaluation with biopsies has the potential to provide a definitive diagnosis and allow the patient to proceed to definitive therapy. Conclusions The GI tract is the most commonly involved site for extranodal lymphoma with the stomach being most frequently involved organ.Chronic Helicobacter pylori infection, celiac disease, inflammatory bowel disease and autoimmune disorders may predispose to GI lymphoma. This heterogenous group of diseases has varied presentations that may mimic several other GI clinico-pathologic entities. GI lymphomas may be diagnosed with appropriately directed endoscopic evaluation coupled with generous tissue sampling and expert pathologic assessment. Management may range from antibiotic therapy, in the case of Helicobacter pylori-associated gastric MALT lymphoma, to chemotherapy with or without radiation and, in rare instances, surgery. There are presently no guidelines to direct endoscopic surveillance of GI lymphomas following treatment.

Tofacitinib for the treatment of moderately to severely active ulcerative colitis: a systematic review, network meta-analysis and economic evaluation

Abstract: Background and aims In the UK, treatments for patients with moderately to severely active ulcerative colitis who have an inadequate response to conventional therapies comprise four biological therapies—the tumour necrosis factor inhibitor (TNFi) agents adalimumab, golimumab and infliximab and the anti-integrin vedolizumab—and an orally administered small molecule therapy, tofacitinib. However, there have been few head-to-head studies of these therapies. This study aimed to compare the clinical and cost-effectiveness of tofacitinib with biological therapies. Methods A systematic literature review was conducted to identify all relevant randomised controlled trial (RCT) evidence. Clinical response, clinical remission and serious infection rates were synthesised using network meta-analysis (NMA). The results were used to compare the cost-effectiveness of tofacitinib and biologics with conventional therapy, using a Markov model, which incorporated lifetime costs and consequences of treatment from a UK National Health Service perspective. Analyses were conducted separately for TNFi-naive and TNFi-exposed populations. Results Seventeen RCTs were used in the NMAs. There were no statistically significant differences among biological therapies and tofacitinib for either TNFi-naive or TNFi-exposed patients. In TNFi-naive patients, all therapies were more efficacious than placebo. In TNFi-exposed patients, only tofacitinib was significantly more efficacious than placebo as induction therapy, and only tofacitinib and vedolizumab were significantly more efficacious than placebo as maintenance therapies. There were no significant differences in serious infection rates among therapies. The incremental cost-effectiveness ratios for tofacitinib versus conventional therapy were £21 338 and £22 816 per quality-adjusted life year (QALY) in the TNFi-naive and TNFi-exposed populations, respectively. TNFi therapies were dominated or extendedly dominated in both populations. Compared with vedolizumab, tofacitinib was associated with a similar number of QALYs, at a lower cost. Conclusion Tofacitinib is an efficacious treatment for moderately to severely active ulcerative colitis and is likely to be a cost-effective use of NHS resources.

Case report and literature review of auto-brewery syndrome: probably an underdiagnosed medical condition

Abstract: Auto-brewery syndrome (ABS), also known as gut fermentation syndrome, is a rarely diagnosed medical condition in which the ingestion of carbohydrates results in endogenous alcohol production. The patient in this case report had fungal yeast forms in the upper small bowel and cecum, which likely fermented carbohydrates to alcohol. Treatment with antifungal agents allowed subsequent ingestion of carbohydrates without symptoms. He had been exposed to a prolonged course of antibiotics before this occurred. We postulate that the antibiotic altered his gut microbiome, allowing fungal growth. This diagnosis should be considered in any patient with positive manifestations of alcohol toxicity who denies alcohol ingestion. The aim of this case report was confirmation and treatment of ABS using a standardised carbohydrate challenge test followed by upper and lower endoscopy to obtain intestinal secretions to detect fungal growth. These fungi were speciated and antifungal sensitivity performed. This allowed the use of appropriate therapy. The patient was kept on a carbohydrate-free diet during the initial 6-week period of therapy. A single-strain probiotic for competitive inhibition of fungal growth was given to the patient. This probiotic was later replaced by a multistrain bacterial probiotic hoping that the multiple bacteria would inhibit fungi better than a single-strain. The beneficial role of probiotics in this condition has not been studied. The patient was rechallenged for endogenous alcohol production prior to reintroducing carbohydrates in his diet.

Genetic polymorphisms in tumour necrosis factor receptors (TNFRSF1A/1B) illustrate differential treatment response to TNFα inhibitors in patients with Crohn's disease.

Abstract: Background Monoclonal antibodies inhibiting tumour necrosis factor-α (TNFα) signalling pathway (anti-TNFα) have been widely used in Crohn’s disease (CD). However, treatment response varies among patients with CD and the clinical outcome is dependent on single nucleotide polymorphisms (SNP) in TNFα receptor superfamily 1A and 1B (TNFRSF1A/1B). Methods We tested nine SNPs in TNFα, TNFRSF1A and TNFRSF1B by TaqMan genotyping from peripheral blood samples of 104 subjects. Additionally, we quantified the effects of these SNPs on their corresponding gene expression by RT-PCR and susceptibility to Mycobacterium avium subsp paratuberculosis (MAP) infection by IS900 nested PCR. Results Four SNPs (TNFα:rs1800629, TNFRSF1A:rs767455, TNFRSF1B:rs1061624 and TNFRSF1B:rs3397) were over-represented significantly (p Conclusion The SNPs TNFRSF1A:rs767455 and TNFRSF1B:rs3397, which are known to affect anti-TNFα clinical outcome in CD, were associated with lower corresponding gene expression and higher MAP infection susceptibility.

Non-alcoholic fatty liver disease with obesity as an independent predictor for incident gastric and colorectal cancer: a population-based longitudinal study.

Abstract: Background Colorectal cancer is known to be an extrahepatic complication of non-alcoholic fatty liver disease (NAFLD). However, the interaction of NAFLD with obesity for incident colorectal cancer has not been clarified yet. Moreover, the effect of NAFLD and obesity for incident gastric cancer has not been clarified yet. Thus, we investigated whether NAFLD with or without obesity would be a risk factor for incident gastric cancer as well as colorectal cancer. Methods The study period was set from 2003 to 2016. NAFLD was diagnosed by abdominal ultrasonography using standardised criteria. We applied the Cox proportional hazards model to investigate the effect of NAFLD with or without obesity at baseline on incident gastric cancer as well as colorectal cancer. Age, sex, lifestyle factors including smoking states, alcohol consumption and exercise, and diabetes were used as covariates. Results During the study period, 27 944 individuals (16 454 men and 11 490 women) were registered in the NAfld in Gifu Area, Longitudinal Analysis study. During the mean (SD) observational period of 2357 (1458) days, incident gastric cancers were diagnosed in 48 individuals (incident rate 0.48 per 1000 person-years) and incident colorectal cancers were diagnosed in 52 individuals (incident rate 0.51 per 1000 person-years). The adjusted HR of NAFLD with obesity for incident gastric cancer was 3.58 (95% CI 1.73 to 7.38, p=0.001) and that for incident colorectal cancer was 2.96 (95% CI 1.73 to 7.38, p=0.003). Conclusion NAFLD with obesity was a risk factor for both incident gastric cancer and colorectal cancer in apparently healthy Japanese individuals.

Gut microbiome meta-analysis reveals dysbiosis is independent of body mass index in predicting risk of obesity-associated CRC

Abstract: Objective Obesity is a risk factor for colorectal cancer (CRC), accounting for more than 14% of CRC incidence. Microbial dysbiosis and chronic inflammation are common characteristics in both obesity and CRC. Human and murine studies, together, demonstrate the significant impact of the microbiome in governing energy metabolism and CRC development; yet, little is understood about the contribution of the microbiome to development of obesity-associated CRC as compared to individuals who are not obese. Design In this study, we conducted a meta-analysis using five publicly available stool and tissue-based 16S rRNA and whole genome sequencing (WGS) data sets of CRC microbiome studies. High-resolution analysis was employed for 16S rRNA data, which allowed us to achieve species-level information to compare with WGS. Results Characterisation of the confounders between studies, 16S rRNA variable region and sequencing method did not reveal any significant effect on alpha diversity in CRC prediction. Both 16S rRNA and WGS were equally variable in their ability to predict CRC. Results from diversity analysis confirmed lower diversity in obese individuals without CRC; however, no universal differences were found in diversity between obese and non-obese individuals with CRC. When examining taxonomic differences, the probability of being classified as CRC did not change significantly in obese individuals for all taxa tested. However, random forest classification was able to distinguish CRC and non-CRC stool when body mass index was added to the model. Conclusion Overall, microbial dysbiosis was not a significant factor in explaining the higher risk of colon cancer among individuals with obesity.

Body image dissatisfaction in patients with inflammatory bowel disease: a systematic review.

Abstract: Background and aims Little is known about the relationship between inflammatory bowel disease (IBD) and body image. The aim of this systematic review was to summarise the evidence on body image dissatisfaction in patients with IBD across four areas: (1) body image tools, (2) prevalence, (3) factors associated with body image dissatisfaction in IBD and (4) association between IBD and quality of life. Methods Two reviewers screened, selected, quality assessed and extracted data from studies in duplicate. EMBASE, MEDLINE, PsycINFO and Cochrane CENTRAL were searched to April 2018. Study design–specific critical appraisal tools were used to assess risk of bias. Narrative analysis was undertaken due to heterogeneity. Results Fifty-seven studies using a body image tool were included; 31 for prevalence and 16 and 8 for associated factors and association with quality of life, respectively. Studies reported mainly mean or median scores. Evidence suggested female gender, age, fatigue, disease activity and steroid use were associated with increased body image dissatisfaction, which was also associated with decreased quality of life. Conclusion This is the first systematic review on body image in patients with IBD. The evidence suggests that body image dissatisfaction can negatively impact patients, and certain factors are associated with increased body image dissatisfaction. Greater body image dissatisfaction was also associated with poorer quality of life. However, the methodological and reporting quality of studies was in some cases poor with considerable heterogeneity. Future IBD research should incorporate measurement of body image dissatisfaction using validated tools.

Aspartate transaminase to platelet ratio index (APRI) but not FIB-5 or FIB-4 is accurate in ruling out significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) in an urban slum-dwelling population.

Abstract: Background and aims Non-invasive assessment of fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) is challenging, especially in resource-limited settings. MR or transient elastography and many patented serum scores are costly and not widely available. There are limited data on accuracy of serum-based fibrosis scores in urban slum-dwelling population, which is a unique group due to its dietary habits and socioeconomic environment. We did this study to compare the accuracy of serum-based fibrosis scores to rule out significant fibrosis (SF) in this population. Methods Histological and clinical data of 100 consecutive urban slum-dwelling patients with NAFLD were analysed. Institutional ethics committee permission was taken. Aspartate transaminase (AST) to platelet ratio index (APRI), fibrosis-4 index (FIB-4) and FIB-5 scores were compared among those with non-significant fibrosis (METAVIR; F0 to F1; n=73) and SF (METAVIR; F2 to F4; n=27). Results AST (IU/mL) (68.3±45.2 vs 23.9±10.9; p Conclusions APRI but not FIB-5 or FIB-4 is accurate in ruling out SF in patients with NAFLD in an urban slum-dwelling population.

Haemostasis treatment using dual red imaging during endoscopic submucosal dissection: a multicentre, open-label, randomised controlled trial.

Abstract: Introduction Patients scheduled to undergo oesophageal, gastric and colorectal endoscopic submucosal dissection (ESD) are to be investigated to verify the efficacy of dual red imaging (DRI) for establishing haemostasis during ESD Methods and analysis The trial is designed as a multicentre, open-label randomised, parallel-group, controlled intervention study Registered patients will be randomly assigned to DRI and white light imaging (WLI) groups In the DRI group, the mucosal incision and submucosal dissection will be performed by WLI, and haemostasis will be managed by DRI when bleeding occurs In the WLI group, the mucosal incision and submucosal dissection are to be performed by WLI and the haemostasis management is to be performed by WLI The primary endpoint is the time from the recognition of bleeding up to the achievement of complete haemostasis (haemostasis time) The secondary endpoints are the operation time, the proportion of cases in which perforation occurs, and the psychological stress experienced by the endoscopist during haemostasis treatment Ethics and dissemination This trial was approved by the Keio University Review Board for Clinical Trials (5 December 2016) Discussion This will be the first multicentre collaborative research using DRI for haemostasis treatment during ESD When the safety and simplicity of DRI as a treatment for haemostasis during ESD can be proven, the ESD procedure can be simplified and disseminated more widely in clinical practice Trial registration number UMIN000025134

Opioid and benzodiazepine prescription among patients with cirrhosis compared to other forms of chronic disease.

Abstract: Objective Data on patterns and correlates of opioid and benzodiazepines prescriptions among patients with chronic conditions are limited. Given a diminished capacity for hepatic clearance, patients with cirrhosis represent a high risk group for use. The aim of this study was to characterise the patterns and correlates of prescription opioid, benzodiazepine and dual drug prescriptions among individuals with common chronic diseases. Design Analysis of Truven Marketscan database to evaluate individuals with drug coverage with cirrhosis (n=169,181), chronic hepatitis C without cirrhosis (n=210 191), congestive heart failure (n=766 840) or chronic obstructive pulmonary disease (n=1 438 798). Pharmacy files were examined for outpatient prescriptions. Results Patients with cirrhosis had a significantly higher prevalence of opioid prescriptions (37.1 per 100 person-years vs 24.3–26.0, p≤0.001) and benzodiazepine prescriptions (21.3 per 100 person-years vs 12.1–12.9, p 90 daily oral morphine equivalents) (29.1% vs 14.4%, p Conclusion Persons with cirrhosis have significantly higher rates of prescription opioid and benzodiazepine prescription compared to others with chronic diseases despite their high risk for adverse drug reactions. Demographics and mental health or substance abuse history can help identify high risk groups to target interventions.

Probiotic L. gasseri strain (LG21) for the upper gastrointestinal tract acting through improvement of indigenous microbiota

Abstract: Objective To describe probiotics including a Lactobacillus gasseri strain LG21 used for the upper gastrointestinal tract, which are considered to act through improvement of indigenous microbiota inhabiting there. Background and design Because the early definition of probiotics emphasized their effects on improving the intestinal microbial ecology, their effects on the intestinal tract and its immunity have been considered common general benefits associated with probiotics. This conclusion was also based on a body of successful clinical trials whose endpoints were the prevention or treatment of intestinal diseases. In contrast to intestinal microbiota, our understanding of the role of gastric microbiota in human health and physiology remains poor, as the bacterial load in the stomach is considered too small to exert a significant effect due to the highly acidic environment of the human stomach. Therefore, the intervention using probiotics in the stomach is still limited at present.Results:In this article using representative 38 quoted articles, we first describe the gastric microbiota, as the indigenous microbiota in the stomach is thought to be significantly involved in the pathophysiology of this organ, since probiotics exert their beneficial effects through improving the resident microbiota. We then review the present status and future prospects of probiotics for the treatment of upper gastrointestinal diseases by quoting representative published articles, including our basic and clinical data. Conclusions Probiotics have been demonstrated to suppress Helicobacter pylori in the stomach, and are also expected to improve functional dyspepsia through the correction of dysbiotic gastric microbiota.

Study protocol for a randomised controlled trial of carvedilol versus variceal band ligation in primary prevention of variceal bleeding in liver cirrhosis (CALIBRE trial)

Abstract: Introduction Liver cirrhosis is the fifth largest cause of adult deaths, and a major complication, variceal bleeding is associated with a 1-year mortality of 40%. There is uncertainty on the first-line therapy for prevention of variceal bleeding owing to a lack of adequately powered trials comparing non-selective beta blockers, in particular carvedilol, with variceal band ligation. Methods and analysis CALIBRE is a multicentre, pragmatic, randomised controlled, open-label trial with an internal pilot. The two interventions are carvedilol 12.5 mg od or variceal band ligation (VBL). Patients with liver cirrhosis and medium to large oesophageal varices that have never bled are eligible for inclusion. The primary outcome is any variceal bleeding within 1 year of randomisation. Secondary endpoints include time to variceal bleed, mortality, transplant-free survival, adverse events, complications of cirrhosis, health-related quality of life, use of healthcare resources, patient preference and use of alternative or crossover therapies. The sample size is 2630 patients over a 4-year recruitment period, across 66 hospitals in the UK. Ethics and dissemination The study has been approved by a National Health Service (NHS) Research Ethics Committee (REC) (reference number 18/NE/0296). The results of this trial will be submitted for publication in a peer reviewed journal. Participants will be informed via a link to a preview of the publication. A lay summary will also be provided via email or posted to participants prior to publication (ISRCTN reference number: 73887615).

Current smoking habits in British IBD patients in the age of e-cigarettes.

Abstract: Background Smoking has a detrimental effect on Crohn’s disease (CD) while data on ulcerative colitis (UC) are conflicting. Smoking habits have changed dramatically in the UK due to a public smoking ban and the advent of e-cigarettes. We describe current smoking rates in patients with inflammatory bowel disease (IBD) and any effects on disease course. Methods Self-reported smoking status was elicited in outpatients with IBD, and clinical data were extracted from patient records. Results Of 465 patients (58% CD, 42% UC), 247 (53.1%) were ever-smokers (37.4% ex-smokers, 15.7% current smokers). Electronic cigarettes (e-cigarettes) were ever used by 28 patients (15 current users). All e-cigarette users had previously smoked cigarettes and 13 had stopped smoking completely. Patients with CD were more likely to currently smoke (21.5% vs 7.7%, p Compared with the general population, the proportion of current cigarette smokers (14.9% vs 15.1%) and e-cigarette users was similar in our cohort (4.26% vs 5.5%). Conclusions Patients with IBD show similar smoking behaviour to the general population. E-cigarettes were used as replacement for cigarettes or by some as an intermediate step for smoking cessation. Larger, prospective studies are required to fully determine the effects of e-cigarettes on IBD.

Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel.

Abstract: Background and aims This article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment. Methods In May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice. Results These recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms. Conclusions Pruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.

Real-world comorbidities and treatment patterns among patients with non-alcoholic fatty liver disease receiving phosphatidylcholine as adjunctive therapy in Russia

Abstract: Objective Previous research conducted in Russia showed that the number of patients with non-alcoholic fatty liver disease (NAFLD) and associated metabolic comorbidities is large. We conducted an observational study to describe the management of NAFLD in patients with metabolic syndrome in Russia. Design A total of 2843 adult patients from 174 medical sites across 6 federal districts of Russia with newly diagnosed NAFLD, who had at least one of four comorbidities, namely overweight/obesity, hypertension, type 2 diabetes mellitus, and hypercholesterolaemia, and who received phosphatidylcholine (PPC) as an adjunctive treatment to standard care, were enrolled during 2015–2016. Results Overall, 2263 patients (79.6%) had at least two metabolic comorbidities associated with NAFLD; overweight/obesity was the most common comorbidity reported in 2298 patients (80.8%). Simple steatosis was the most frequently identified clinical form of NAFLD, diagnosed in 2128 patients (74.9%). Among hypertensive patients, ACE inhibitors, statins, and sartans were most commonly prescribed. Biguanides were administered in more than half of diabetic patients. In patients with overweight/obesity and hypercholesterolaemia, statins were the most frequently prescribed medications. Almost all patients (2837/2843; 99.8%) were treated with 1.8 g of PPC three times per day. PPC therapy was associated with a 90.5% 6-month compliance rate, high treatment satisfaction, and a favourable safety profile. However, almost 15% of diabetic patients and 40% of overweight/obese patients received no further treatment. Conclusions In Russia, patients with newly diagnosed NAFLD represent a population heavily burdened by comorbidities, mainly overweight/obesity and hypercholesterolaemia. A significant part of these patients did not receive a comprehensive pharmacotherapy, highlighting the existing unmet need in the current management of NAFLD patients with metabolic syndrome in Russia.

Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndrome

Abstract: Objective The plasma-based methylated SEPTIN9 (mSEPT9) is a colorectal cancer (CRC) screening test for adults aged 50–75 years who are at average risk for CRC and have refused colonoscopy or faecal-based screening tests. The applicability of mSEPT9 for high-risk persons with Lynch syndrome (LS), the most common hereditary CRC condition, has not been assessed. This study sought preliminary evidence for the utility of mSEPT9 for CRC detection in LS. Design Firstly, SEPT9 methylation was measured in LS-associated CRC, advanced adenoma, and subject-matched normal colorectal mucosa tissues by pyrosequencing. Secondly, to detect mSEPT9 as circulating tumor DNA, the plasma-based mSEPT9 test was retrospectively evaluated in LS subjects using the Epi proColon 2.0 CE assay adapted for 1mL plasma using the “1/1 algorithm”. LS case groups included 20 peri-surgical cases with acolonoscopy-based diagnosis of CRC (stages I-IV), 13 post-surgical metastatic CRC, and 17 pre-diagnosis cases. The control group comprised 31 cancer-free LS subjects. Results Differential hypermethylation was found in 97.3% (36/37) of primary CRC and 90.0% (18/20) of advanced adenomas, showing LS-associated neoplasia frequently produce the mSEPT9 biomarker. Sensitivity of plasma mSEPT9 to detect CRC was 70.0% (95% CI, 48%-88%)in cases with a colonoscopy-based CRC diagnosis and 92.3% (95% CI, 64%-100%) inpost-surgical metastatic cases. In pre-diagnosis cases, plasma mSEPT9 was detected within two months prior to colonoscopy-based CRC diagnosis in 3/5 cases. Specificity in controls was 100% (95% CI 89%-100%). Conclusion These preliminary findings suggest mSEPT9 may demonstrate similar diagnostic performance characteristics in LS as in the average-risk population, warranting a well-powered prospective case–control study.

Association of fatty liver disease with mortality outcomes in an Eastern Finland male cohort

Abstract: Objective Fatty liver disease (FLD) has been associated with extrahepatic morbidity outcomes. However, reports on the association of FLD, assessed using fatty liver index (FLI), with mortality outcomes have been inconsistent. Our objective was to examine the effect of metabolic factors (blood pressure, insulin, fasting glucose, lipoproteins) on the associations of FLI with mortality outcomes among middle-aged men. Study design Prospective cohort study. Methods Our subjects were 1893 men at baseline from 1984 to 1989 in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort. Multivariable Cox regression models were used to analyse the association of baseline FLI, with the HRs for all-cause, disease, cardiovascular, non-cardiovascular and cancer mortality outcomes. Results The mean FLI in the FLI categories were 16.2 in the low and reference category (FLI Conclusion High FLI (FLD) is associated with increased risks of mortality outcomes. The FLI-CVD mortality association can be largely explained by metabolic factors. Persons with FLD should be monitored for metabolic deterioration and extrahepatic morbidity to improve their prognoses.

Volumetric laser endomicroscopy features of dysplasia at the gastric cardia in Barrett's oesophagus: results from an observational cohort study.

Abstract: Objective Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used in Barrett’s oesophagus (BE) to help identify dysplasia in the oesophagus. VLE criteria exist for oesophageal dysplasia but not for dysplasia in the gastric cardia. The aim of this study was to determine if there are in vivo VLE features that can predict gastric cardia dysplasia in BE. Design This was a single-centre observational cohort study from August 2016 to August 2018. Patients were included if they had BE, were undergoing a VLE exam as standard of care, and had a suspicious target laser marked at the gastric cardia. The following VLE features were correlated to histology to determine if an association existed between histology subtype and VLE feature: wide crypts, irregular surface, one large isolated gland, multiple glands, and complex glands. Results A total of 110 in vivo gastric cardia targets in 77 patients with BE were analysed. The following abnormalities were identified: 61 wide crypts, 34 isolated glands, 16 irregular surfaces, 15 multiple glands, and 11 complex glands. Complex glands were the only VLE feature that correlated to any histology subtype. They were present in 71% of targets with high-grade dysplasia (HGD), T1a cancer or T1b cancer and had a sensitivity, specificity, and accuracy of 71%, 99%, and 85%, respectively. Of the 10 patients with complex glands on VLE and HGD/cancer on histology, 4 had a normal-appearing mucosa (40%) on endoscopy. Conclusion Identification of complex glands on VLE may aid in detection of HGD or early cancer in the gastric cardia in BE. This is particularly important, as dysplasia at the gastric cardia can be difficult to see endoscopically.

Effects of preoperative endoanal ultrasound on functional outcome after anal fistula surgery.

Abstract: Objective Endoanal ultrasound (EAUS) is a recommended preoperative investigation for fistula-in-ano (FiA) which aims to provide the best chance of healing and preservation of continence function. This study aims are (1) to assess effect of EAUS on functional outcome and (2) to determine factors associated with clinical outcomes after FiA surgery. Design Retrospective analysis of subjects with cryptogenic FiA between January 2011 and December 2016, in a tertiary hospital, was performed by comparing EAUS and no-EAUS groups. Postoperative change in St. Mark’s faecal incontinence severity score (cFISS=FISS at 6 months after surgery–FISS before surgery) were compared. General linear model was used to determine factors associated with cFISS. Binary logistic regression was used to assess factors related to clinical outcomes. A p-value of Results We enrolled 339 subjects; 109 (M:F 91:18, mean age 41.7±13.6 years) of 115 in EAUS group and 230 in no-EAUS group (M:F 195:35, mean age 42.6±13.0 years). There were higher proportions of recurrent cases (24.8% vs 13.9%, p=0.014) and complex FiA (80.7% vs 50.4%, p=0.001) in EAUS group. Postoperative FISS (mean±SE) were increased in both groups; preoperative versus postoperative FISS were 0.36±0.20 versus 0.59±0.25 in EAUS group (p=0.056) and 0.31±0.12 versus 0.76±0.17 in no-EAUS group (p Conclusion EAUS had favourable effects on functional outcome after FiA surgery while multiple factors were associated with clinical outcomes. EAUS is useful, accurate, inexpensive and can be the first tool for planning of complex and recurrent FiA.

Cytomegalovirus colitis in inflammatory bowel disease and after haematopoietic stem cell transplantation: diagnostic accuracy, predictors, risk factors and disease outcome

Abstract: Background Concurrent cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) and after haematopoietic stem cell transplantation (HSCT) is an important clinical entity associated with high rates of morbidity and mortality. Methods A retrospective study of 47 patients with IBD and 61 HSCT patients was performed regarding the evaluation of diagnostic accuracy of applied methods, predictors, risk factors for CMV disease manifestation, the proportion of patients with antiviral treatment and disease outcome. Results The sensitivity of quantitative PCR (qPCR) with a cut-off value of >250 copies/mg for CMV colitis in patients with IBD and HSCT patients was 79% and 92%, respectively. Predictors for CMV colitis in the IBD cohort were anaemia and the presence of endoscopic ulcers. Glucocorticoids, calcineurin inhibitors and >2 concurrent lines of treatment with immunosuppressive drugs could be identified as risk factors for CMV colitis in the IBD cohort with an OR of 7.1 (95% CI 1.7 to 29.9), 21.3 (95% CI 2.4 to 188.7) and 13.4 (95% CI 3.2 to 56.1), respectively. Predictors and risk factors for CMV gastroenteritis in the HSCT cohort was the presence of endoscopic ulcers (OR 18.6, 95% CI 3.3 to 103.7) and >2 concurrent lines of treatment with immunosuppressive drugs. Antiviral therapy was administered in 70% of patients with IBD and 77% of HSCT patients with CMV disease. 71% of antiviral-treated patients with IBD showed an improvement of their disease activity and 14% underwent colectomy. The mortality rate of HSCT patients was 21% irrespective of their CMV status. Conclusions In addition to the implementation of histological methods, qPCR may be performed in patients with suspected high-risk IBD and HSCT patients for CMV colitis. Independent validations of these results in further prospective studies are needed.