First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases:A 2020 Delphi consensus

Ulcerative colitis and Crohn’s disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract.The incidence and prevalence are on the rise worldwide,and the heterogeneity between patients and within individuals over time is striking.The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients.This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence-and expert opinion-based recommendations.Comprehensive up-to-date guidance is provided regarding diagnosis,evaluation of disease severity,appropriate and timely use of different investigations,choice of appropriate therapy for induction and remission phase according to disease severity,and management of main complications.

Endoscopic papillary large balloon dilatation with sphincterotomy is safe and effective for biliary stone removal independent of timing and size of sphincterotomy

AIM To describe the efficacy and safety of endoscopic papillary large balloon dilatation(EPLBD) in the management of bile duct stones in a Western population. METHODS Data was collected from the endoscopic retrograde cholangiopancreatography(ERCP) and Radiology electronic database along with a review of case notes over a period of six years from 1 st August 2009 to 31 st July 2015 and incorporated into Microsoft excel. Statistical analyses were performed using Med Calc for Windows,version 12.5(Med Calc Software,Ostend,Belgium). Simple statistical applications were applied in order to determine whether significant differences exist in comparison groups. We initially used simple proportions to describe the study populations. Furthermore,we used chi-square test to compare proportions and categorical variables. Non-parametric Mann-Whitney U-test was applied in order to compare continuous variables. All comparisons were deemed to be statistically significant if P values were less than 0.05.RESULTS EPLBD was performed in 229 patients(46 females) with mean age of 68 ± 14.3 years. 115/229(50%) patients had failed duct clearance at previous ERCP referred from elsewhere with standard techniques. Duct clearance at the Index* ERCP(1 st ERCP at our centre) was 72.5%. Final duct clearance rate was 98%. EPLBD after fresh sphincterotomy was performed in 81(35.4%). Median balloon size was 13.5 mm(10-18). In addition to EPLBD,per-oral cholangioscopy(POC) and electrohydraulic lithotripsy(EHL) was performed in 35(15%) patients at index* ERCP. 63(27.5%) required repeat ERCP for stone clearance. 28(44.5%) required POC and EHL and 11(17.4%) had repeat EPLBD for complete duct clearance. Larger stone size(12.4 mm vs 17.4 mm,P < 0.000001),multiple stones(2,range(1-13) vs 3,range(1-12),P < 0.006) and dilated common bile duct(CBD)(12.4 mm vs 18.3 mm,P < 0.001) were significant predictors of failed duct clearance at index ERCP. 47 patients(20%) had ampullary or peri-ampullary diverticula. Procedure related adverse events included 2 cases of bleeding and pancreatitis(0.87%) each.CONCLUSION EPLBD is a safe and effective technique for CBDS removal. There is no difference in outcomes whether it is performed at the time of sphincterotomy or at a later procedure or whether there is a full or limited sphincterotomy.

Translational approaches: From fatty liver to non-alcoholic steatohepatitis

Over the past few decades, non-alcoholic fatty liver disease(NAFLD) has become one, if not the most common,cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early age is the most worrying aspect of this pathology, since it provides more time for its evolution. The spectrum of this disease ranges from liver steatosis to steatohepatitis, fibrosis and in some cases, hepatocellular carcinoma. NAFLD may not always be considered a benign disease and hepatologists must be cautious in the presence of fatty liver. This should prompt the use of the available experimental models to understand better the pathogenesis and to develop a rational treatment of a disease that is dangerously increasing. In spite of the growing efforts, the pathogenesis of NAFLD is still poorly understood. In the present article we review the most relevant hypotheses and evidence that account for the progression of NAFLD to non-alcoholic steatohepatitis(NASH) and fibrosis. The available in vitro and in vivo experimental models of NASH are discussed and revised in terms of their validity in translational studies. These studies must be aimed at the discovery of the still unknown triggers or mediators that induce the progression of hepatic inflammation, apoptosis and fibrosis.

Gastrointestinal neuromuscular apparatus: An underestimated target of gut microbiota

Over the last few years, the importance of the resident intestinal microbiota in the pathogenesis of several gastrointestinal diseases has been largely investigated. Growing evidence suggest that microbiota can influence gastrointestinal motility. The current working hypothesis is that dysbiosis-driven mucosal alterations induce the production of several inflammatory/immune mediators which affect gut neuro-muscular functions. Besides these indirect mucosal-mediated effects, the present review highlights that recent evidence suggests that microbiota can directly affect enteric nerves and smooth muscle cells functions through its metabolic products or bacterial molecular components translocated from the intestinal lumen. Tolllike receptors, the bacterial recognition receptors, are expressed both on enteric nerves and smooth muscle and are emerging as potential mediators between microbiota and the enteric neuromuscular apparatus. Furthermore, the ongoing studies on probiotics support the hypothesis that the neuromuscular apparatus may represent a target of intervention, thus opening new physiopathological and therapeutic scenarios.

Management of primary achalasia: The role of endoscopy

Achalasia is an oesophageal motor disorder which leads to the functional obstruction of the lower oesophageal sphincter(LES) and is currently incurable. The main objective of all existing therapies is to achieve a reduction in the obstruction of the distal oesophagus in order to improve oesophageal transit, relieve the symptomatology, and prevent long-term complications. The most common treatments used are pneumatic dilation(PD) and laparoscopic Heller myotomy, which involves partial fundoplication with comparable shortterm success rates. The most economic non-surgical therapy is PD, with botulinum toxin injections reserved for patients with a higher surgical risk for whom the former treatment option is unsuitable. A new technology is peroral endoscopic myotomy, postulated as a possible non-invasive alternative to surgical myotomy. Other endoluminal treatments subject to research more recently include injecting ethanolamine into the LES and using a temporary self-expanding metallic stent. At present, there is not enough evidence permitting a routine recommendation of any of these three novel methods. Patients must undergo follow-up after treatment to guarantee that their symptoms are under control and to prevent complications. Most experts are in favour of some form of endoscopic follow-up, however no established guidelines exist in this respect. The prognosis for patients with achalasia is good, although a recurrence after treatment using any method requires new treatment.

Portal vein cannulation:An uncommon complication of endoscopic retrograde cholangiopancreatography

Portal vein cannulation is a rare complication of endo-scopic retrograde cholangiopancreatography(ERCP).It has been reported that it usually occurs after endo-scopic sphincterotomy,whereas in cases without prior sphincterotomy,the presence of portobiliary fistulas has been shown.Here,we present a case in which cannulation of the portal vein occurred despite careful wire-guided cannulation and the absence of sphinc-terotomy.Although fatal cases of cerebral and pulmo-nary air and/or bile embolism have been reported in patients with combined portal and hepatic vein trauma after ERCP and sphincterotomy,isolated portal vein cannulation,as in the current case,does not usu-ally result in mortality or serious morbidity.However,awareness of this rare complication is important so that no further intervention is performed.

Management of nonalcoholic fatty liver disease:An evidence-based clinical practice review

AIM:To build a consensus among Chilean specialists on the appropriate management of patients with nonalcoholic fatty liver disease(NAFLD)in clinical practice.METHODS:NAFLD has now reached epidemic proportions worldwide.The optimal treatment for NAFLD has not been established due to a lack of evidence-based recommendations.An expert panel of members of the Chilean Gastroenterological Society and the Chilean Hepatology Association conducted a structured analysis of the current literature on NAFLD therapy.The quality of the evidence and the level of recommendations supporting each statement were assessed according to the recommendations of the United States Preventive Services Task Force.A modified three-round Delphi technique was used to reach a consensus among the experts.RESULTS:A group of thirteen experts was established.The survey included 17 open-ended questions that were distributed among the experts,who assessed the articles associated with each question.The levels of agreement achieved by the panel were 93.8%in the first round and 100%in the second and third rounds.The final recommendations support the indication of lifestyle changes,including diet and exercise,for all patients with NAFLD.Proven pharmacological therapies include only vitamin E and pioglitazone,which can be used in nondiabetic patients with biopsy-proven nonalcoholic steatohepatitis(the progressive form of NAFLD),although the long-term safety and efficacy of these therapies have not yet been established.CONCLUSION:Current NAFLD management is rapidly evolving,and new pathophysiology-based therapies are expected to be introduced in the near future.All NAFLD patients should be evaluated using a three-focused approach that considers the risks of liver disease,diabetes and cardiovascular events.

Clinical usefulness of adherence to gastro-esophageal reflux disease guideline by Spanish gastroenterologists

AIM:To investigate usefulness of adherence to gastroesophageal reflux disease(GERD) guideline established by the Spanish Association of Gastroenterology.METHODS:Prospective,observational and multicentre study of 301 patients with typical symptoms of GERD who should be managed in accordance with guidelines and were attended by gastroenterologists in daily practice.Patients(aged > 18 years) were eligible for inclusion if they had typical symptoms of GERD(heartburn and/or acid regurgitation) as the major complaint in the presence or absence of accompanying atypical symptoms,such as dyspeptic symptoms and/or supraesophageal symptoms.Diagnostic and therapeutic decisions should be made based on specific recommendations of the Spanish clinical practice guideline for GERD which is a widely disseminated and well known instrument among Spanish in digestive disease specialists.RESULTS:Endoscopy was indicated in 123(41%) patients:50 with alarm symptoms,32 with age > 50 years without alarm symptom.Seventy-two patients(58.5%) had esophagitis(grade A,23,grade B,28,grade C,18,grade D,3).In the presence of alarm symptoms,endoscopy was indicated consistently with recommendations in 98% of cases.However,in the absence of alarm symptoms,endoscopy was indicated in 33% of patients > 50 years(not recommended by the guideline).Adherence for proton pump inhibitors(PPIs) therapy was 80%,but doses prescribed were lower(half) in 5% of cases and higher(double) in 15%.Adherence regarding duration of PPI therapy was 69%;duration was shorter than recommended in 1%(4 wk in esophagitis grades C-D) or longer in 30%(8 wk in esophagitis grades A-B or in patients without endoscopy).Treatment response was higher when PPI doses were consistent with guidelines,although differences were not significant(95% vs 85%).CONCLUSION:GERD guideline compliance was quite good although endoscopy was over indicated in patients > 50 years without alarm symptoms;PPIs were prescribed at higher doses and longer duration.

Role of capsule endoscopy in suspected celiac disease: A European multi-centre study

AIM To analyze the diagnostic yield(DY), therapeutic impact(TI) and safety of capsule endoscopy(CE).METHODS This is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease(CD)(mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy(Group-Ⅰ, n = 19), seropositive CD without atrophy(Group-Ⅱ, n = 39), contraindication to gastroscopy(Group-Ⅲ, n = 6), seronegative CD without atrophy, but with a compatible context(Group-Ⅳ, n = 99). DY, TI and the safety of CE were analysed.RESULTS The overall DY was 54% and the final diagnosis was villous atrophy(n = 65, 39.9%), complicated CD(n = 12, 7.4%) and other enteropathies(n = 11, 6.8%; 8 Crohn's). DY for groups Ⅰ to Ⅳ was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases(36.9%), diffuse in 19(29.2%), jejunal in 11(16.9%), and patchy in 10 cases(15.4%). Factors associated with a greater DY were positive serology(68.3% vs 49.2%, P = 0.034) and older age(P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE resultschanged the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI(92.3% vs 45.3%, P < 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention(0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD.CONCLUSION CE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD.

Current role of capsule endoscopy in Crohn's disease

Capsule endoscopy(CE) currently plays an important role in Crohn's disease(CD). It is a noninvasive technique that has led to a breakthrough in the endoscopic diagnosis of diseases of the small intestine. Its superior diagnostic performance and excellent safety profile lead to its considerable acceptance on the part of the patient. This paper reviews current indications of CE in three stages of clinical practice: Suspected CD, unclassified colitis and its extensive role in diagnosed CD. The diagnostic and therapeutic impact of the results of CE on the monitoring of this disease is also reviewed. Knowledge of its applications, the interpretation of its results in an appropriate context and the existence of a validated endoscopic activity index could change the way in which these patients are managed. The definition of mucosal healing and postoperative recurrence by means of endoscopic scoring systems will endow CE with new applications in the management of CD in the near future.

Towards a new paradigm of microscopic colitis: Incomplete and variant forms

Microscopic colitis(MC) is a chronic inflammatory bowel disease that has emerged in the last three decades as a leading cause of chronic watery diarrhoea. MC classically includes two main subtypes: lymphocytic colitis(LC) and collagenous colitis(CC). Other types of histopathological changes in the colonic mucosa have been described in patients with chronic diarrhoea, without fulfilling the conventional histopathological criteria for MC diagnosis. Whereas those unclassified alterations remained orphan for a long time, the use of the term incomplete MC(MCi) is nowadays universally accepted. However, it is still unresolved whether CC, LC and MCi should be considered as one clinical entity or if they represent three related conditions. In contrast to classical MC, the real epidemiological impact of MCi remains unknown, because only few epidemiological studies and case reports have been described. MCi presents clinical characteristics indistinguishable from complete MC with a good response to budesonide and cholestiramine. Although a number of medical treatments have been assayed in MC patients, currently, there is no causal treatment approach for MC and MCi, and only empirical strategies have been performed. Further studies are needed in order to identify their etiopathogenic mechanisms, and to better classify and treat MC.

Very-early-stage Hepatocellular Carcinoma,Are We at Long Last on Route for Achieving Better Patient Outcomes?

Hepatocellular carcinoma(HCC)represents∼90%of the primary liver cancer cases,and 90%of HCC cases occur in patients with chronic liver disease.1 It also represents the sixth most common cancer(4.7%)and the third leading cause of cancer-related death globally(8.3%).2 More troubling,the global incidence and mortality rates have been increasing since 1990.3 In the United States,the highest average annual percentage change(known as AAPC)reported between 2000 and 2012 involved individuals between 55 and 59 years of age(AAPC:8.9%;95%confidence interval:7.1–10.7%).