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For decades the rationale for treatment of gastro-oesophageal reflux disease (GORD) with acid suppressors, such as proton pump inhibitors (PPIs), was that symptoms were attributable to reflux of acidic stomach contents into the oesophagus. However, recent advances in the understanding of how brain–gut interactions can modulate the perception of visceral stimuli have complicated the concept of GORD.1 It is increasingly evident that altered perception of reflux is an important underlying cause of symptoms.2 A number of syndromes related to visceral hypersensitivity and central nervous system dysregulation are now recognised as ‘functional’ gastrointestinal (GI) disorders, potentially localised to the oesophagus,3 bowel, stomach, duodenum, anorectum, gallbladder, or multiple GI sites in the same patient. These functional syndromes are common; an internet-based health survey of almost 6000 adults in the US, Canada, and the UK found that 35% had symptoms compatible with some functional GI disorder and 7% met diagnostic criteria for a functional oesophageal disorder.4 This could potentially account for a large fraction of the adults with weekly reflux symptoms in population-based assessments (global prevalence ∼13%).5 However, it being impractical to investigate all of these patients, the recognition of altered perception as a major determinant of reflux symptoms has had little impact on management in general practice. To provide guidance for the management of uninvestigated reflux symptoms in primary care, a series of sponsored (Reckitt Benckiser Healthcare Ltd, UK) workshops were held among gastroenterologists, GI surgeons, and GPs. The objective was to translate recent research findings into clinical practice strategies. Epidemiological data suggest that the prevalence of GORD has increased considerably since the mid-1990s. However, wider public awareness of the link between reflux symptoms and oesophageal cancer6 has likely contributed to the increased presentation of symptomatic patients in primary care. Additionally, the more we understand the …

ObjectiveDue to an annual progression rate of Barrett’s oesophagus (BO) with low-grade dysplasia (LGD) between 9% and 13% per year endoscopic ablation therapy is preferred to surveillance. Since this recommendation is based on only one randomised trial, we aimed at checking these results by another multicentre randomised trial with a similar design.DesignA prospective randomised study was performed in 14 centres comparing radiofrequency ablation (RFA) (maximum of 4 sessions) to annual endoscopic surveillance, including patients with a confirmed diagnosis of BO with LGD. Primary outcome was the prevalence of LGD at 3 years. Secondary outcomes were the prevalence of LGD at 1 year, the complete eradication of intestinal metaplasia (CE-IM) at 3 years, the rate of neoplastic progression at 3 years and the treatment-related morbidity.Results125 patients were initially included, of whom 82 with confirmed LGD (76 men, mean age 62.3 years) were finally randomised, 40 patients in the RFA and 42 in the surveillance group. At 3 years, CE-IM rates were 35% vs 0% in the RFA and surveillance groups, respectively (pConclusionRFA modestly reduced the prevalence of LGD as well as progression risk at 3 years. The risk-benefit balance of endoscopic ablation therapy should therefore be carefully weighted against surveillance in patients with BO with confirmed LGD.Trial registration numberNCT01360541.

BEST PRACTICE ADVICE 1: A diagnosis of functional heartburn should be considered when retrosternal burning pain or discomfort persists despite maximal (double-dose) proton pump inhibitor (PPI) therapy taken appropriately before meals during a 3-month period. BEST PRACTICE ADVICE 2: A diagnosis of functional heartburn requires upper endoscopy with esophageal biopsies to rule out anatomic and mucosal abnormalities, esophageal high-resolution manometry to rule out major motor disorders, and pH monitoring off PPI therapy (or pH-impedance monitoring on therapy in patients with proven gastroesophageal reflux disease [GERD]), to document physiologic levels of esophageal acid exposure in the distal esophagus with absence of reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 3: Overlap of functional heartburn with proven GERD is diagnosed according to Rome IV criteria when heartburn persists despite maximal PPI therapy in patients with history of proven GERD (ie, positive pH study, erosive esophagitis, Barrett's esophagus, or esophageal ulcer), and pH impedance testing on PPI therapy demonstrates physiologic acid exposure without reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 4: PPIs have no therapeutic value in functional heartburn, the exception being proven GERD that overlaps with functional heartburn. BEST PRACTICE ADVICE 5: Neuromodulators, including tricyclic antidepressants, selective serotonin reuptake inhibitors, tegaserod, and histamine-2 receptor antagonists have benefit as either primary therapy in functional heartburn or as add-on therapy in functional heartburn that overlaps with proven GERD. BEST PRACTICE ADVICE 6: Based on available evidence, acupuncture and hypnotherapy may have benefit as monotherapy in functional heartburn, or as adjunctive therapy combined with other therapeutic modalities. BEST PRACTICE ADVICE 7: Based on available evidence, anti-reflux surgery and endoscopic GERD treatment modalities have no therapeutic benefit in functional heartburn and should not be recommended.

Per-oral endoscopic myotomy (POEM) is effective in achalasia. The objective of this study was to evaluate the short-term clinical efficacy of POEM in non-achalasia esophageal motility disorders (NAEMD). Patients with NAEMD diagnosed by high-resolution manometry were included in a retrospective multicentric study. For each individual case, two controls paired on gender and age were matched: one with type I/II achalasia and one with type III achalasia. The clinical response, defined by an Eckardt score ≤ 3, was assessed at 3 and 6 months. Ninety patients (mean age 66 years, 57 men) were included, 30 patients with NAEMD (13 jackhammer esophagus, 6 spastic esophageal disorders, 4 nutcracker esophagus, and 7 esophagogastric junction obstruction), 30 patients with type I–II achalasia, and 30 patients with type III achalasia. The 3-month response rates were 80% (24/30), 90% (27/30), and 100% (30/30) in NAEMD, type I–II achalasia and type III achalasia, respectively (p

Home parenteral nutrition (HPN) is the recommended treatment in patients with chronic intestinal failure (CIF). HPN is associated with a worsening of patients' quality of life and has a dramatic impact on personal and familial daily life. Little is known about the informal caregiver burden of patients receiving HPN.To assess informal caregiver burden and the factors associated with moderate-to-severe caregiver burden in patients treated with HPN.Informal caregivers of consecutive patients treated with HPN in a French nutrition referral center were invited to participate in a survey between January 2021 and June 2021. They had to fill out an anonymous standardized self-questionnaire evaluating burden by the Zarit Burden Interview (ZBI) and depression and anxiety symptoms by the Hospital Anxiety and Depression Scale (HADS) score since HPN introduction.Among the 87 HPN patients having informal caregivers, 53 (61%) completed the questionnaire. Thirty (57%) informal caregivers were women. The caregiver's median age was 62 years (IQR, 21.0). Twelve (22%) expressed moderate to severe burden (ZBI score, 41-88). In a multivariate analysis, the caregiver's male gender (odds ratio [OR], 16.45; 95% CI, 2.30-238.75; P = 0.014) and the number of simultaneous infusions per day1 (OR, 9.92; 95% CI, 1.35-121.60; P = 0.0038) were associated with a moderate to severe burden. Twenty caregivers reported anxious and depressive symptoms with an elevated HADS score.In this prospective survey, a minority of informal caregivers of patients with CIF being treated with HPN expressed moderate to severe burden. The caregiver's male gender was associated with a higher burden in patients with CIF.

BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

Summary Background Quadruple therapy using a single capsule formulation of bismuth, metronidazole and tetracycline (BMT; Pylera®), associated with omeprazole for the eradication of Helicobacter pylori, represents the reintroduction of bismuth in France after 40 years. Objective To describe the real-life patterns of use of BMT following a request from the French health authorities. Methods Patients with a first BMT dispensing (index date, ID), with one year of data before and after ID, were identified in the French nationwide claims database 1/97 sample. Misuse of BMT was defined as dispensing >1 pack of BMT at ID or absence of a diagnostic test in the preceding year. Results In total, 540 patients were included. Prescribers were gastroenterologists (n = 243; 45%) and general practitioners (n = 160; 30%). A proton pump inhibitor was co-dispensed to 504 patients (96%). Ten patients (2%) had contraindications to BMT. Fifty-nine patients (11%) met the misuse criteria: ten (2%) were dispensed > 1 pack of BMT and 49 (9%) had not had a diagnostic test for H. pylori in the previous year. During follow-up, 27 patients (5%) required retreatment (treatment failure). Conclusion In this real-life study, most patients were dispensed only one pack of BMT, consistent with recommendations. Misuse related principally to the absence of prior diagnostic test for H. pylori.

Esophageal hypomotility disorders manifest with abnormal esophageal body contraction vigor, breaks in peristaltic integrity, or failure of peristalsis in the context of normal lower esophageal sphincter relaxation on esophageal high-resolution manometry (HRM). The Chicago Classification version 4.0 recognizes two hypomotility disorders, ineffective esophageal motility (IEM) and absent contractility, while fragmented peristalsis has been incorporated into the IEM definition. Updated criteria for ineffective swallows consist of weak esophageal body contraction vigor measured using distal contractile integral (DCI, 100-450 mmHg·cm·s), transition zone defects >5 cm measured using a 20 mmHg isobaric contour, or failure of peristalsis (DCI < 100 mmHg·cm·s). More than 70% ineffective swallows and/or ≥50% failed swallows are required for a conclusive diagnosis of IEM. When the diagnosis is inconclusive (50%-70% ineffective swallows), supplementary evidence from multiple rapid swallows (absence of contraction reserve), barium radiography (abnormal bolus clearance), or HRM with impedance (abnormal bolus clearance) could support a diagnosis of IEM. Absent contractility requires 100% failed peristalsis, consistent with previous versions of the classification. Consideration needs to be given for the possibility of achalasia in absent contractility with dysphagia despite normal IRP, and alternate complementary tests (including timed upright barium esophagram and functional lumen imaging probe) are recommended to confirm or refute the presence of achalasia. Future research to quantify esophageal bolus retention on stationary HRM with impedance and to understand contraction vigor thresholds that predict bolus clearance will provide further refinement to diagnostic criteria for esophageal hypomotility disorders in future iterations of the Chicago Classification.

AIM Low anterior resection syndrome (LARS) following sphincter-preserving surgery for rectal cancer has a high prevalence, with an impact on long-term bowel dysfunction and quality of life. We designed the bowel rehabilitation programme (BOREAL) as a proactive strategy to assess and treat patients with LARS. The BOREAL programme consists of a stepwise approach of escalating treatments: medical management (steps 0-1), pelvic floor physiotherapy, biofeedback and transanal irrigation (step 2), sacral nerve neuromodulation (step 3), percutaneous endoscopic caecostomy and anterograde enema (step 4) and definitive colostomy (step 5). METHODS A pilot study was undertaken to assess the feasibility of collecting LARS data routinely with the parallel implementation of the BOREAL programme. All patients who underwent total mesorectal excision for rectal cancer between February 2017 and March 2019 were included. LARS was assessed using the LARS score and the Wexner Faecal Incontinence score at 30 days and 3, 6, 9 and 12 months postoperatively. A good functional result was considered to be a combined LARS score

Sleep is involved in the regulation of inflammation, healing, and digestion. The pathophysiology of Crohn’s disease (CD) is unclear, and the role of sleep disturbances has recently been suggested. The present study investigated a putative association between sleep disturbances and CD activity. We conducted a prospective observational monocenter translational study, recruiting major CD patients from 2013 to 2015. Disease activity was assessed by the Harvey-Bradshaw index and the CD activity index. Objective sleep quantity and quality were measured by wrist actigraphy over a period of 7 days. The primary objective was to look for an association between wrist actigraphy parameters and CD activity. Thirty-four CD patients, including 14 with active disease and 20 in remission, were included. Sleep efficiency measured by wrist actigraphy was lower in patients with active CD compared to patients in remission. Wake after sleep onset time best predicted CD activity with an AUROC of 0.83. Patients with active CD were more frequently characterized as “poor sleepers” and frequently suffered from excessive daytime sleepiness. Sleep efficiency is lower in patients with active CD than in those in remission. Further studies aimed at better characterizing CD patients’ sleep are warranted.

BACKGROUND The low FODMAPs (fermentable oligo-, di-, monosaccharides, and polyols) diet improves lower gastrointestinal symptoms. Patients suffering from proton pump inhibitor (PPI) refractory gastroesophageal reflux disease (GERD) have limited treatment options. We investigated the efficacy of a low FODMAPs diet in patients with PPI refractory GERD. METHODS This multicenter, randomized, open-label study compared the efficacy of a 4-week low FODMAPs diet and usual dietary advice (ie, low-fat diet and head of bed elevation) in patients with symptomatic PPI refractory GERD, defined by a Reflux Disease Questionnaire (RDQ) score >3 and abnormal pH-impedance monitoring on PPIs. The primary endpoint was the percentage of responders (RDQ ≤3) at the end of the diet. RESULTS Thirty-one patients (55% women, median age 45 years) were included, 16 randomized in the low FODMAPs diet group and 15 in the usual dietary advice group. Adherence to the assigned diet was good, with a significant difference in the FODMAPs intake per day between the low FODMAPs diet (2.5 g) and the usual dietary advice group (13 g) (p

BACKGROUND: Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis. METHODS: A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements. RESULTS: The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT4 receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:9 issue:3 pages:287-306 ispartof: location:England status: published

BACKGROUND High-resolution impedance manometry (HRIM) evaluates esophageal peristalsis and bolus transit. We used esophageal impedance integral (EII), the ratio between bolus presence before and after an expected peristaltic wave, to evaluate predictors of bolus transit. METHODS From HRIM studies performed on 61 healthy volunteers (median age 27 years, 48%F), standard metrics were extracted from each of 10 supine water swallows: distal contractile integral (DCI, mmHg cm s), integrated relaxation pressure (IRP, mmHg), and breaks in peristaltic integrity (cm, using 20 mmHg isobaric contour). Pressure and impedance coordinates for each swallow were exported into a dedicated, python-based program for EII calculation (EII ratio ≥ 0.3 = abnormal bolus clearance). Univariate and multivariate analyses were performed to assess predictors of abnormal bolus clearance. KEY RESULTS Of 591 swallows, 80.9% were intact, 10.5% were weak, and 8.6% failed. Visual analysis overestimated abnormal bolus clearance compared to EII ratio (p ≤ 0.01). Bolus clearance was complete (median EII ratio 0.0, IQR 0-0.12) in 82.0% of intact swallows in contrast to 53.3% of weak swallows (EII ratio 0.29, IQR 0.0-0.57), and 19.6% of failed swallows (EII ratio 0.5, IQR 0.34-0.73, p

Aim: Little is known about the pathophysiology of low anterior resection syndrome (LARS), and evidence concerning the management of patients diagnosed with this condition is scarce. The aim of the LARS Expert Advisory Panel was to develop practical guidance for healthcare professionals dealing with LARS. Method: The ‘Management guidelines for low anterior resection syndrome’ (MANUEL) project was promoted by a team of eight experts in the assessment and management of patients with LARS. After a face-to-face meeting, a strategy was agreed to create a comprehensive, practical guide covering all aspects that were felt to be clinically relevant. Eight themes were decided upon and working groups established. Each working group generated a draft; these were collated by another collaborator into a manuscript, after a conference call. This was circulated among the collaborators, and it was revised following the comments received. A lay patient revised the manuscript, and contributed to a section containing a patient's perspective. The manuscript was again circulated and finalized. A final teleconference was held at the end of the project. Results: The guidance covers all aspects of LARS management, from pathophysiology, to assessment and management. Given the lack of sound evidence and the often poor quality of the studies, most of the recommendations and conclusions are based on the opinions of the experts. Conclusions: The MANUEL project provides an up-to-date practical summary of the available evidence concerning LARS, with useful directions for healthcare professional and patients suffering from this debilitating condition.

Background Esophagogastric junction contractile integral (EGJ-CI) and EGJ morphology are high-resolution manometry (HRM) metrics that assess EGJ barrier function. Normative data standardized across world regions and HRM manufacturers are limited. Methods Our aim was to determine normative EGJ metrics in a large international cohort of healthy volunteers undergoing HRM (Medtronic, Laborie, and Diversatek software) acquired from 16 countries in four world regions. EGJ-CI was calculated by the same two investigators using a distal contractile integral-like measurement across the EGJ for three respiratory cycles and corrected for respiration (mm Hg cm), using manufacturer-specific software tools. EGJ morphology was designated according to Chicago Classification v3.0. Median EGJ-CI values were calculated across age, genders, HRM systems, and regions. Results Of 484 studies (28.0 years, 56.2% F, 60.7% Medtronic studies, 26.0% Laborie, and 13.2% Diversatek), EGJ morphology was type 1 in 97.1%. Median EGJ-CI was similar between Medtronic (37.0 mm Hg cm, IQR 23.6-53.7 mm Hg cm) and Diversatek (34.9 mm Hg cm, IQR 22.1-56.1 mm Hg cm, P = 0.87), but was significantly higher using Laborie equipment (56.5 mm Hg cm, IQR 35.0-75.3 mm Hg cm, P < 0.001). 5(th) percentile EGJ-CI values ranged from 6.9 to 12.1 mm Hg cm. EGJ-CI values were consistent across world regions, but different between manufacturers even within the same world region (P = 0.3) but higher in women (P < 0.001). Conclusions EGJ morphology is predominantly type 1 in healthy adults. EGJ-CI varies widely in health, with significant gender influence, but is consistent within each HRM system. Manufacturer-specific normative values should be utilized for clinical HRM interpretation.

Background and Aims Acid exposure time (AET) and reflux episode thresholds from the Lyon Consensus may not apply for pH impedance studies performed while on proton pump inhibitor (PPI) therapy. We aimed to determine metrics from “on PPI” pH impedance studies predicting need for escalation of therapy. Methods De-identified pH impedance studies performed while on twice-daily PPI (Diversatek, Boulder, CO) in healthy volunteers (n = 66, median age 37.5 years, 43.9% female), and patients with proven gastroesophageal reflux disease (GERD) (European heartburn-predominant cohort: n = 43, median age 57.0 years, 55.8% female; North American regurgitation-predominant cohort: n = 42, median age 41.6 years, 42.9% female) were analyzed. Median values and interquartile ranges for pH impedance metrics in healthy volunteers were compared with proven GERD patients with and without 50% symptom improvement on validated measures. Receiver operating characteristic (ROC) analyses identified optimal thresholds predicting symptom response. Results Both conventional and novel reflux metrics were similar between PPI responders and nonresponders (P ≥ .1 for each) despite differences from healthy volunteers. Combinations of metrics associated with conclusively abnormal reflux burden (AET >4%, >80 reflux episodes) were seen in 32.6% and 40.5% of heartburn and regurgitation-predominant patients, respectively, 57.1% and 82.4% of whom reported nonresponse; and 85% with these metrics improved with invasive GERD management. On ROC analysis, AET threshold of 0.5% modestly predicted nonresponse (sensitivity, 0.62; specificity, 0.51; P = .22), and 40 reflux episodes had better performance characteristics (sensitivity, 0.80; specificity, 0.51; P = .002); 79% with these metrics improved with invasive GERD management. Conclusion Combinations of abnormal “on PPI” pH impedance metrics are associated with PPI nonresponse in proven GERD patients, and can be targeted for treatment escalation, including surgery, particularly in regurgitation-predominant GERD.

International audience; BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ. © 2020 John Wiley & Sons Ltd, National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK: P01 DK092217, National Institute of Diabetes and Digestive and Kidney Diseases, Grant/Award Number: P01 DK092217

Up to 40% of patients with symptoms suspicious of gastroesophageal reflux disease (GERD) do not respond completely to proton pump inhibitor (PPI) therapy. The term “refractory GERD” has been used loosely in the literature. A distinction should be made between refractory symptoms (ie, symptoms may or may not be GERD-related), refractory GERD symptoms (ie, persisting symptoms in patients with proven GERD, regardless of relationship to ongoing reflux), and refractory GERD (ie, objective evidence of GERD despite adequate medical management). The present ESNM/ANMS consensus paper proposes use the term “refractory GERD symptoms” only in patients with persisting symptoms and previously proven GERD by either endoscopy or esophageal pH monitoring. Even in this context, symptoms may or may not be reflux related. Objective evaluation, including endoscopy and esophageal physiologic testing, is requisite to provide insights into mechanisms of symptom generation and evidence of true refractory GERD. Some patients may have true ongoing refractory acid or weakly acidic reflux despite PPIs, while others have no evidence of ongoing reflux, and yet others have functional esophageal disorders (overlapping with proven GERD confirmed off therapy). In this context, attention should also be paid to supragastric belching and rumination syndrome, which may be important contributors to refractory symptoms.

When esophageal acid exposure time (AET) is physiologic, ROME IV stratifies functional esophageal disorders into functional heartburn (FH, with negative reflux-symptom association) and reflux hypersensitivity (RH, with positive reflux-symptom association), and hypothesizes that FH/RH could overlap with proven gastroesophageal reflux disease (GERD). We compared conventional FH/RH diagnosed off antisecretory therapy with overlap FH/RH coexisting with proven GERD.Adult patients with heartburn underwent pH-impedance testing on therapy (proven GERD) and off therapy (unproven GERD) and completed validated questionnaires defining symptoms (Reflux Diagnostic Questionnaire, RDQ), affective state (Hospital Anxiety and Depression Scale, HADS; Visceral Sensitivity Index, VSI), and functional diagnoses (irritable bowel syndrome, IBS; functional dyspepsia, FD on ROME diagnostic questionnaire). AET (pathologic:6%, physiologic4%) and mean nocturnal baseline impedance (MNBI) were calculated. Clinical, psychological, and functional profiles were compared between FH and RH and to a comparison cohort of non-erosive reflux disease (NERD, AET 6%).Study patients included 19 with RH (10 with overlap RH), 60 with FH (31 with overlap FH), and 26 patients with NERD. Clinical, psychological, and functional profiles of conventional FH/RH were similar to overlap FH/RH. Compared with NERD, combined FH and RH cohorts had higher anxiety scores, and lower proportions with IBS. Compared with FH with low MNBI, FH defined using both normal AET and normal MNBI had higher depression scores (p = 0.008), and trended toward higher anxiety scores (p = 0.059).Conventional and overlap FH and RH have similar clinical, psychological and functional profiles, thereby proving ROME IV hypotheses.

Medico-economic data of patients suffering from chronic nausea and vomiting are lacking. In these patients, gastric electrical stimulation (GES) is an effective, but costly treatment. The aim of this study was to assess the efficacy, safety and medico-economic impact of Enterra therapy in patients with chronic medically refractory nausea and vomiting.Data were collected prospectively from patients with medically refractory nausea and/or vomiting, implanted with an Enterra device and followed for two years. Gastrointestinal quality of life index (GIQLI) score, vomiting frequency, nutritional status and safety were evaluated. Direct and indirect expenditure data were prospectively collected in diaries.Complete clinical data were available for142 patients (60 diabetic, 82 non-diabetic) and medico-economic data were available for 96 patients (36 diabetic, 60 non-diabetic), 24 months after implantation. GIQLI score increased by 12.1 ± 25.0 points (p.001), with a more significant improvement in non-diabetic than in diabetic patients (+15.8 ± 25.0 points, p.001 versus 7.3 ± 24.5 points, p = .027, respectively). The proportion of patients vomiting less than once per month increased by 25.5% (p.001). Hospitalisations, time off work and transport were the main sources of costs. Enterra therapy decreased mean overall healthcare costs from 8873 US$ to 5525 US$ /patient/year (p = .001), representing a saving of 3348 US$ per patient and per year. Savings were greater for diabetic patients (4096 US$ /patient/year) than for non-diabetic patients (2900 US$ /patient/year).Enterra therapy is an effective, safe and cost-effective option for patients with refractory nausea and vomiting.gov Identifier: NCT00903799.

Background Oesophageal radiofrequency reduces use of proton pump inhibitors (PPIs) in patients with gastro-oesophageal reflux disease responding to PPIs. Aim To determine the efficacy of oesophageal radiofrequency in patients with PPI-refractory heartburn. Methods A randomised, double-blind, sham-controlled multicentre study was designed to assess the efficacy of oesophageal radiofrequency in PPI non-responding patients with heartburn. Patients had moderate-to-severe heartburn defined by at least 3 occurrences a week, and not improved by continuous PPI treatment. The primary endpoint was clinical success at week 24, defined by intake of less than 7 PPI doses over the 2 preceding weeks and adequate symptom control determined by the patient. Results Sixty two patients were randomised, 29 to the oesophageal radiofrequency group and 33 to the sham group. Intention-to-treat analysis showed that 1/29 (3.4%) and 5/33 (15.1%) achieved the primary endpoint in the oesophageal radiofrequency and sham groups, respectively (NS). There was no significant difference between oesophageal radiofrequency and sham regarding the number of days without heartburn, days with PPI consumption in the last 2 weeks, and patients not taking PPIs. No pH-impedance parameter was associated with clinical response. The occurrence of adverse events was similar in both groups. Conclusion This sham-controlled, randomised study did not demonstrate any efficacy of oesophageal radiofrequency for the treatment of PPI-refractory heartburn regarding symptom relief or consumption of PPIs. ClinicalTrials.gov NCT01682265.

BACKGROUND The definition and relevance of ineffective esophageal motility (IEM) remains debated. Our aim was to determine motility patterns and symptoms associated with IEM defined as impaired bolus clearance. METHODS To define altered bolus clearance, normal range of swallows with complete bolus transit (CBT) on high-resolution impedance manometry (HRIM) was determined in 44 asymptomatic controls. The results were then applied to a cohort of 81 patients with esophageal symptoms to determine the motility patterns which best predicted altered bolus clearance. Subsequently, in a cohort of 281 consecutive patients the identified motility patterns were compared with patients' customary symptoms. KEY RESULTS In asymptomatic controls, the normal range of swallows with CBT was 50%-100%. In patients, altered bolus transit (

There have been conflicting results from trials of gastric electrical stimulation (GES) for treatment of refractory vomiting, associated or not with gastroparesis. We performed a large, multicenter, randomized, double-blind trial with crossover to study the efficacy of GES in patients with refractory vomiting, with or without gastroparesis.For 4 months, we assessed symptoms in 172 patients (66% women; mean age ± standard deviation, 45 ± 12 years; 133 with gastroparesis) with chronic (12 months) of refractory vomiting (idiopathic, associated with a type 1 or 2 diabetes, or postsurgical). A GES device was implanted and left unactivated until patients were randomly assigned, in a double-blind manner, to groups that received 4 months of stimulation parameters (14 Hz, 5 mA, pulses of 330 μs) or no stimulation (control); 149 patients then crossed over to the other group for 4 months. Patients were examined at the end of each 4-month period (at 5 and 9 months after implantation). Primary endpoints were vomiting score, ranging from 0 (daily vomiting) to 4 (no vomiting), and the quality of life, assessed by the Gastrointestinal Quality of Life Index scoring system. Secondary endpoints were changes in other digestive symptoms, nutritional status, gastric emptying, and control of diabetes.During both phases of the crossover study, vomiting scores were higher in the group with the device on (median score, 2) than the control group (median score, 1; P.001), in diabetic and nondiabetic patients. Vomiting scores increased significantly when the device was ON in patients with delayed (P.01) or normal gastric emptying (P = .05). Gastric emptying was not accelerated during the ON period compared with the OFF period. Having the GES turned on was not associated with increased quality of life.In a randomized crossover study, we found that GES reduced the frequency of refractory vomiting in patients with and without diabetes, although it did not accelerate gastric emptying or increase of quality of life. Clinicaltrials.gov, Number: NCT00903799.

In case reports or small studies, percutaneous endoscopic caecostomy (PEC) has been proposed as an alternative to the Malone intervention to perform antegrade colonic enemas. Our goal was to assess the feasibility, efficacy, and tolerance of PEC in a large group of patients with refractory colorectal functional disorders. From September 2006 to April 2014, all patients undergoing PEC for constipation, fecal incontinence, and incontinence after rectal resection in two expert centers were studied. The PEC procedure consisted in anchoring the caecum to the abdominal wall (caecopexy) and placing a specifically designed tube in the colonic lumen to perform antegrade enemas. The quality of life (GIQLI), constipation (Kess), and incontinence (Cleveland) scores were assessed before PEC and at 3, 6, 12, and 24 months. A total of 69 patients were included. GIQLI scores were significantly improved in constipation group (n = 43), incontinence group (n = 19), and rectal resection group (n = 10). In the constipation group, Kess score decreased from 25.9 before PEC to 20.6 at 2 years (p = 0.01). In the incontinence and post-rectal resection groups, Cleveland scores decreased from 14.3 before PEC to 2.7 at 6 months (p = 0.01) and to 10.4 at 2 years (p = 0.04). Overall, PEC was considered successful by patients in 58%, 74%, and 90% of cases, in constipation, incontinence, and rectal resection groups, respectively. Chronic pain (52%) at the catheter site was the most frequent complication. Percutaneous endoscopic caecostomy for antegrade colonic enemas improves significantly the quality of life of patients with colorectal disorder refractory to medical treatment.

Globus is a non-painful sensation of a tightness or a lump/foreign body in the throat that is not associated with dysphagia and may actually improve during meals. While several otorhinolaryngologic, thyroid, and esophageal disorders have been linked to globus, cause-and-effect relationships are difficult to establish. Consequently, though part of the evaluation, objective otorhinolaryngologic and esophageal testing is often negative. The presence of alarm symptoms, particularly pain, weight loss, dysphagia, or odynophagia is indications for objective testing. A diagnosis of idiopathic globus requires exclusion of pharyngeal, laryngeal, and esophageal disorders with laryngoscopy, endoscopy, high-resolution manometry, barium radiography, and/or ambulatory reflux monitoring. A trial of acid-suppressive therapy may be reasonable in the absence of alarm symptoms, especially if concurrent reflux symptoms are identified. Ablation of heterotopic gastric mucosa in the proximal esophagus has been reported to improve globus symptoms. Beyond these specific approaches, further management of idiopathic globus consists of reassurance, neuromodulators, and complementary approaches. Globus has a benign course with no long-term consequences, and the overall prognosis is good as the magnitude of symptoms may decline over time.

International audience; BACKGROUND:According to infliximab (IFX) license in Crohn's disease (CD), infusion doses are based on patient's body-weight. Dose banding providing standardized doses (SD) has been implemented in parenteral chemotherapy in order to optimize aseptic unit capacity and reduce drug expenditure, duration of hospital stay and costs without decreasing efficacy.MATERIAL AND METHOD:The first part was a single-center retrospective analysis of consecutive CD patients receiving IFX maintenance therapy to determine standardized doses covering more than 50% of infusions. The second part was a prospective cohort study assessing the impact of SD compared to body-weight doses (BWD) on admission duration and costs.RESULTS:Six IFX SD covering more than 90% of infusion doses were implemented for dose banding. According to the Monte-Carlo simulation, there was no significant difference between IFX SD and BWD maintenance regimens. When assessed prospectively in 116 patients (75 patients treated with SD and 41 with BWD) corresponding to 128 infusions, hospitalization duration was shortened by 70 min per patient (p

The purpose of this review is to outline the recent developments in the field of extraesophageal reflux disease and provide clinically relevant recommendations. The recommendations outlined in this review are based on expert opinion and on relevant publications from PubMed and EMbase. The Clinical Practice Updates Committee of the American Gastroenterological Association proposes the following recommendations: Best Practice Advice 1: The role of a gastroenterologist in patients referred for evaluation of suspected extra esophageal symptom is to assess for gastroesophageal etiologies that could contribute to the presenting symptoms. Best Practice Advice 2: Non-GI evaluations by ENT, pulmonary and/or allergy are essential and often should be performed initially in most patients as the cause of the extraesophageal symptom is commonly multifactorial or not esophageal in origin. Best Practice Advice 3: Empiric therapy with aggressive acid suppression for 6-8 weeks with special focus on response of the extraesophageal symptoms can help in assessing association between reflux and extraesophageal symptoms. Best Practice Advice 4: No single testing methodology exists to definitively identify reflux as the etiology for the suspected extra esophageal symptoms. Best Practice Advice 5: Constellation of patient presentation, diagnostic test results and response to therapy should be employed in the determination of reflux as a possible etiology in extra esophageal symptoms. Best Practice Advice 6: Testing may need to be off or on proton pump inhibitor (PPI) therapy depending on patients' presenting demographics and symptoms in assessing the likelihood of abnormal gastroesophageal reflux. A. On therapy testing may be considered in those with high probability of baseline reflux (those with previous esophagitis, Barrett's esophagus or abnormal pH). B. Off therapy testing may be considered in those with low probability of baseline reflux with the goal of identifying moderate to severe reflux at baseline. Best Practice Advice 7: Lack of response to aggressive acid suppressive therapy combined with normal pH testing off therapy or impedance-pH testing on therapy significantly reduces the likelihood that reflux is a contributing etiology in presenting extraesophageal symptoms. Best Practice Advice 8: Surgical fundoplication is discouraged in those with extra esophageal reflux symptoms unresponsive to aggressive PPI therapy. Best Practice Advice 9: Fundoplication should only be considered in those with a mechanical defect (e.g., hiatal hernia), moderate to severe reflux at baseline off PPI therapy who have continued reflux despite PPI therapy and have failed more conservative non-GI treatments.

Total mesorectal excision and preoperative radiotherapy in mid and low rectal cancer allow us to achieve very good oncological results. However, major and refractory low anterior resection syndrome and fecal incontinence alter the quality of life of patients with a long expected life span.We assessed the functional results of patients treated by antegrade enema for refractory low anterior resection syndrome and fecal incontinence after total mesorectal excision.This is a prospective monocentric study from 2012 to 2016.Patients who underwent percutaneous endoscopic cecostomy for refractory low anterior resection syndrome and fecal incontinence after total mesorectal excision were prospectively analyzed.We assessed the morbidity of the procedure and compared low anterior resection syndrome score, Wexner score, and Gastrointestinal Quality of Life Index before and after the use of antegrade enema.Of 25 patients treated by antegrade enema over the study period, 6 (24%) had a low anterior resection, 18 (72%) had a coloanal anastomosis, and 1 (4%) had a perineal colostomy. Postoperatively, the rate of local abscess was 8%, all treated by antibiotics. Low anterior resection syndrome score (33 vs 4, p0.001), Wexner score (16 vs 4, p0.001), and Gastrointestinal Quality of Life Index (73 vs 104, p0.001) were all significantly improved after antegrade enema. The 2 main symptoms reported by patients were sweating (28%) and local pain (36%). At the end of the follow-up, 16% (n = 4) catheters were removed, and the rate of definitive colostomy was 12% (n = 3).The main limitations of this study are the monocentric features and the sample size.Antegrade enema for major and refractory low anterior resection syndrome and fecal incontinence after total mesorectal excision appears to be a promising treatment to avoid definitive colostomy. See Video Abstract at http://links.lww.com/DCR/A608.

Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD in isolation, but are of value in determining need for further investigation. Conclusive evidence for reflux on oesophageal testing include advanced grade erosive oesophagitis (LA grades C and D), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal oesophageal acid exposure time (AET) >6% on ambulatory pH or pH-impedance monitoring. A normal endoscopy does not exclude GERD, but provides supportive evidence refuting GERD in conjunction with distal AET

In most patients presenting without alarm features, gastro-oesophageal reflux disease (GORD) is diagnosed empirically, based on symptoms assessment and response to medical therapy, mainly proton pump inhibitors (PPIs). Despite its low specificity (placebo response) and the risk of PPI overuse, the empiric PPI trial is cost-effective and recommended as a first line strategy when GORD is suspected.1 Additional testing is indicated when empiric treatment fails to provide adequate symptom relief and/or prior antireflux surgery. In 2017, the so-called ‘Lyon consensus’ experts proposed guidelines for GORD diagnosis based on the results of endoscopy and ambulatory pH (impedance) monitoring. Briefly, these experts considered as a conclusive diagnosis of GORD the presence of Los Angeles grade C/D oesophagitis, peptic stricture, long-segment Barrett’s mucosa or acid exposure time (AET) superior to 6% on pH monitoring. An AET below 4% is considered as definitely normal, and consequently, the experts acknowledged the possibility of an inconclusive diagnosis in patients with an AET between 4% and 6%: the ‘grey area’. In this situation, considering additional parameters (baseline impedance, histology, oesophageal motility abnormalities) may help to shrink this area as much as possible. In Gut , Rusu et al report the results of a study which …

Gastroesophageal reflux disease encompasses a wide spectrum of disorders related to the reflux of gastric contents into the esophagus. Extraesophageal reflux (EER) may be suspected in patients with unexplained chronic cough, pharyngolaryngeal symptoms, and asthma. For physicians, suspected EER is challenging as there is currently no tool that can reliably make a definitive diagnosis. Endoscopic signs are not specific, pharyngeal and proximal reflux monitoring are not reliable, and if distal pH or pH-impedance monitoring can identify patients with abnormal reflux, they cannot predict the response to therapy. Controlled randomized trials have failed to reliably demonstrate any benefit of high-dose proton-pump inhibitors over placebo in patients with laryngeal symptoms, chronic cough, and asthma. Overall, the role of gastroesophageal reflux has been largely overestimated in patients with suspected EER. Especially when proton-pump inhibitors failed to improve symptoms, other diagnosis should be considered, such as functional laryngeal disorders which are probably much more prevalent in these patients than pathologic gastroesophageal reflux.

Background Improvement of quality of life is a main objective in inflammatory bowel disease [IBD] management. Data on sexual dysfunction [SD] in IBD are scarce. This study compared rates of SD between IBD patients and healthy controls [HC], and searched for predictors of SD. Methods All consecutive IBD patients seen in two tertiary centres during 2 months were invited to fill an anonymous validated questionnaire on their sexual function [Female Sexual Index Function and International Index of Erectile Function]. The same questionnaires were filled by HC and by patients with irritable bowel syndrome [IBS] enrolled as a second comparative group. Results In all, 358 IBD patients filled the questionnaire [192 women]-including 238 with Crohn's disease and 120 with ulcerative colitis-and 110 HC [54 women] and 107 IBS patients [54 women]. In women, SD rates were 53.6% in IBD vs 28% in HC [p < 0.01] and 77.5% in IBS [p = 0.10] patients; in men, figures were 16.9% in IBD, 7.4% in HC [p = 0.64], and 26.4% in IBS [p = 0.60]. An erectile dysfunction [ED] was reported by 43% of IBD patients, 13% of HC [p < 0.01] and 55% of IBS patients [p = 0.60 vs IBD]. Predictors of SD and ED were social and emotional functioning, anxiety in women and depression in men. IBD activity was not associated with SD. Conclusions In IBD, 54% of women have an SD and 43% of men an ED. These rates are significantly higher than in HC, mostly driven by psychological factors, and independent from disease severity.

A fixed-dose association of bismuth subcitrate, metronidazole and tetracycline (BMT) (Pylera®, Allergan, NJ, USA) was made available in France in 2013 for the eradication of Helicobacter pylori. Due to a historical issue of bismuth encephalopathy, the French Health Authorities requested a study of blood and plasma bismuth concentrations with BMT in daily practice. The aim of the study was to measure eventual bismuth accumulation and neurological toxicity in patients prescribed BMT. Patients initiating BMT for H. pylori between March 2014 and December 2015 were included. A blood sample was taken before first BMT intake and 24 h after the last intake, for assay of bismuth. A concentration > 50 μg/L was considered abnormal. Neurological complaints were assessed at inclusion, at the end of the 10-day treatment course, and 28 days later. 202 patients were included, of whom 190 took at least one dose of BMT, and 167 provided both required blood samples. Mean blood bismuth concentrations after the BMT course were 16.9 μg/L (95% confidence interval 15.6–18.3). Concentrations were > 50 μg/L (56.0 μg/L and 50.9 μg/L) in two elderly patients, one of whom presented mild, transient memory impairment during treatment. Non-serious neurological symptoms occurred in 20% of all patients and treatment failure was documented in 5% of patients. In this study measuring blood bismuth concentrations in real-life practice, in 50 μg/L. No serious neurological adverse events were observed. EU-PAS register EUPAS3142 at www.encepp.eu ; ENCePP study seal.

BACKGROUND Almost no prospective data on endoscopy in MUTYH monoallelic carriers are available. OBJECTIVE This study aimed to define the prevalence of colorectal and duodenal adenomas in a population of people presenting with a single mutation of the MUTYH gene and being first-degree relatives of biallelic MUTYH mutation carriers. DESIGN This study is a prospective cohort evaluation. PATIENTS Patients were first-degree relatives of a patient who had polyposis with biallelic MUTYH mutation and carrying a single gene mutation of the gene from 12 French centers. SETTINGS This is a multicenter study. INTERVENTION Detailed data on life habits (tobacco, alcohol, and nonsteroidal anti-inflammatory drugs), extraintestinal manifestations, and germline analysis were recorded. Complete endoscopic evaluation (colonoscopy and upper endoscopy) with chromoendoscopy was performed. RESULTS Sixty-two patients were prospectively included (34 women (55%), mean age of 54, range 30-70 years). Thirty-two patients (52%) presented with colorectal polyps at colonoscopy. Of these patients with polyps, 15 (25%) had only adenomas, 8 (13%) had only hyperplastic polyps, 1 (1%) had sessile serrated adenomas, and 8 (13%) had adenomas and/or sessile serrated adenomas. We detected, in total, 29 adenomas with low-grade dysplasia, 5 adenomas with high-grade dysplasia, and 6 sessile serrated adenomas. Fourteen patients (23%) presented with a single adenoma, and 10 (16%) had 1 to 5 adenomas. No patient had more than 5 adenomas. At upper endoscopy, 3 had a limited number of fundic gland polyps; none had duodenal adenomas. The 2 main missense mutations c.1145G>A, p.Gly382Asp and c.494A>G, p.Tyr165Cys were associated with the development of colorectal adenomas/serrated polyps in these monoallelic carriers. LIMITATIONS This study was limited by the small number of patients. CONCLUSIONS This prospective study provides unique prospective data suggesting that monoallelic mutation carriers related to patients with polyposis show no colorectal polyposis and have very limited upper GI manifestations justifying an endoscopic follow-up. See Video Abstract at http://links.lww.com/DCR/A862.

Background & Aims Most patients with Crohn's disease (CD) eventually require an intestinal resection. However, CD frequently recurs after resection. We performed a randomized trial to compare the ability of infliximab vs placebo to prevent CD recurrence. Methods We evaluated the efficacy of infliximab in preventing postoperative recurrence of CD in 297 patients at 104 sites worldwide from November 2010 through May 2012. All study patients had undergone ileocolonic resection within 45 days before randomization. Patients were randomly assigned (1:1) to groups given infliximab (5 mg/kg) or placebo every 8 weeks for 200 weeks. The primary end point was clinical recurrence, defined as a composite outcome consisting of a CD Activity Index score >200 and a ≥70-point increase from baseline, and endoscopic recurrence (Rutgeerts score ≥i2, determined by a central reader) or development of a new or re-draining fistula or abscess, before or at week 76. Endoscopic recurrence was a major secondary end point. Results A smaller proportion of patients in the infliximab group had a clinical recurrence before or at week 76 compared with the placebo group, but this difference was not statistically significant (12.9% vs 20.0%; absolute risk reduction [ARR] with infliximab, 7.1%; 95% confidence interval: -1.3% to 15.5%; P =.097). A significantly smaller proportion of patients in the infliximab group had endoscopic recurrence compared with the placebo group (30.6% vs 60.0%; ARR with infliximab, 29.4%; 95% confidence interval: 18.6% to 40.2%; P

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

With the development of high-resolution manometry and specific metrics to characterize esophageal motility, the Chicago Classification has become the gold standard for the diagnosis of esophageal motor disorders. Major and significant disorders, that is, never observed in healthy subjects, are achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, absent peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is relevant to predict the response to endoscopic and surgical therapies as several studies suggest that, pneumatic dilation is less effective than Heller myotomy, in type III achalasia. Peroral endoscopic myotomy, initially developed in expert centers, is a promising technique for the treatment of achalasia. The medical therapeutic options for distal esophageal spasm and hypercontractile esophagus are smooth muscle relaxants and pain modulators. Intraesophageal injection of botulinum toxin might be an interesting option for treatment of these disorders but further studies are required to determine the optimal injection protocol and the best candidates based on manometric patterns. The treatment of hypotensive motility disorders is disappointing and relies mainly on dietary and lifestyle changes as no effective esophageal prokinetic is currently available.

Psoriasiform eruptions are a classical adverse skin reaction of tumour necrosis factor (TNF)-α inhibitors. The aim of this study was to identify the association between the severity or pattern of psoriasiform reactions and the underlying disease. A retrospective study was conducted between January 2012 and May 2015. Adult patients who developed psoriasiform eruptions whilst being treated with TNFα inhibitors were included. For each patient, 3 independent blinded dermatologists graded twice the severity of the lesions according to 6 clinical psoriasiform eruption types. Inter- and intra-individual kappa tests were performed to evaluate the robustness of the scoring system. The association between severity score levels or the pattern of reactions and the underlying disease was assessed. The severity scoring system showed good inter- and intra-observer reproducibility. Women patients treated with TNFα inhibitors for inflammatory bowel diseases showed a higher risk of developing severe reactions with scalp and skin-fold involvement.

Oesophageal dysphagia is a common symptom, which might be related to severe oesophageal diseases such as carcinomas. Therefore, an organic process must be ruled out in the first instance by endoscopy in all patients presenting with dysphagia symptoms. The most prevalent obstructive aetiologies are oesophageal cancer, peptic strictures and eosinophilic oesophagitis. Eosinophilic oesophagitis is one of the most common causes of dysphagia in adults and children, thus justifying the need to obtain oesophageal biopsy samples from all patients presenting with unexplained dysphagia. With the advent of standardized high-resolution manometry and specific metrics to characterize oesophageal motility, the Chicago classification has become a gold-standard algorithm for manometric diagnosis of oesophageal motor disorders. In addition, sophisticated investigations and analysis methods that combine pressure and impedance measurement are currently in development. In the future, these techniques might be able to detect subtle pressure abnormalities during bolus transport, which could further explain pathophysiology and symptoms. The degree to which novel approaches will help distinguish dysphagia caused by motor abnormalities from functional dysphagia still needs to be determined.

Background & Aims Combined pH and impedance monitoring can detect all types of reflux episodes within the esophageal lumen and the pharynx. We performed a multicenter study to establish normal values of pharyngeal and esophageal pH-impedance monitoring in individuals on and off therapy and to determine the interobserver reproducibility of this technique. Methods We collected ambulatory 24-hour pH-impedance recordings from 46 healthy subjects by using a bifurcated probe that allowed for detection of reflux events in the distal and proximal esophagus and pharynx. Data were collected when subjects had not received any medicine (off therapy) and after receiving 40 mg esomeprazole twice daily for 14 days (on therapy). The interobserver agreement for the detection of reflux events was determined in 20 subjects off and on therapy. Results were expressed as median (interquartile range). Results Off therapy, subjects had a median of 32 reflux events (17–45) in the distal esophagus and 3 (1–6) in the proximal esophagus; they had none in the pharynx. On therapy, subjects had a median number of 21 reflux events (6–37) in the distal esophagus and 2 (0–5) in the proximal esophagus; again, there were none in the pharynx. Interobserver agreement was good for esophageal reflux events but poor for pharyngeal events. Conclusions We determined normal values of pharyngeal and gastroesophageal reflux events by 24-hour pH-impedance monitoring of subjects receiving or not receiving esomeprazole therapy. Analyses of esophageal events were reproducible, but analyses of pharyngeal events were not; this limitation should be taken into account in further studies. Eudract.ema.europa.eu, Number: 2010-022845-48.

Eosinophilic esophagitis is a major cause of dysphagia and esophageal food impaction in young adults, although the diagnostic can be made in older patients. The diagnosis of eosinophilic esophagitis is suspected on endoscopic abnormalities of esophageal mucosa and confirmed by esophageal biopsy samples. Approximately 50% of patients with eosinophilic esophagitis do respond to proton pump inhibitors therapy. The first line therapy for eosinophilic esophagitis is proton pump inhibitor therapy. Ingested topical steroids represent a second-line therapy. The practical modalities of this treatment should be clearly explained to patients. A diet that eliminates most alimentary allergens provide a 75% clinical and histological remission rate. The progressive reintroduction protocol allows to identify the allergen(s) involved in the disease. Endoscopic dilatations should be proposed in patients with significant esophageal stricture.

Background The role of gastroesophageal reflux in chronic laryngeal symptoms is difficult to establish. The aim of this study was to characterize pharyngeal and esophageal pH–impedance reflux patterns in a group of patients with suspected laryngopharyngeal reflux and to determine predictive factors of response to proton pump inhibitors. Methods Patients with chronic pharyngolaryngeal symptoms were evaluated with a symptom score questionnaire, laryngoscopy, and 24-hour pharyngeal and esophageal pH–impedance monitoring at baseline and after 8-week treatment with esomeprazole 40 mg b.i.d. Response to treatment was defined by a diminution of more than 50% of the score for the primary symptom. Reflux patterns and baseline impedance values were compared to those obtained in 46 healthy subjects. Key Results Twenty-four patients were included (17 women, median age 54 years), all previously refractory to antisecretory therapy. Symptom scores were 46 (32–62) and 40 (27–76) off and on therapy, respectively (P=.1). There was no significant difference between patients and controls for pH–impedance reflux parameters and baseline values off and on therapy in distal and proximal esophagus and in the pharynx. Median numbers of pharyngeal reflux were 0 and 0 off and on therapy, respectively. Only two patients were responders to treatment, both with excessive distal reflux but no pharyngeal reflux. Only one patient had abnormal pharyngeal reflux but did not respond to proton pump inhibitors. Conclusions Patients with suspected laryngopharyngeal reflux refractory to therapy do not exhibit abnormal pharyngeal or esophageal pH–impedance reflux. In these patients, laryngopharyngeal reflux is unlikely.

International audience; Faecal microbiota transplantation is effective for treating recurrent forms of Clostridium difficile infection and its use in this indication is recommended in the most recent European and North American guidelines. In this context, faecal microbiota transplantation is beginning to be performed in France in clinical practice, while the rules governing this procedure have been defined in France only for clinical trials. To unify, secure, and evaluate practice in this field in France, the French Group of Faecal microbiota Transplantation (FGFT) was created in October 2014 with the support of the French National Society of Gastroenterology, the French Infectious Disease Society, and the National Academy of Pharmacy. We present here the deliberations of this group regarding the use of faecal microbiota transplantation for recurrent Clostridium difficile infection. The issues addressed are the indications, therapeutic sequence, delivery procedures, donor selection, methods and conditions of specimen preparation, and traceability.

Introduction Cyclosporine (CsA) is an effective agent for treating patients with acute steroid-refractory ulcerative colitis (UC). The aim was to assess endoscopic and histologic responses to CsA and to determine their predictive value on UC outcome. Patients and methods Consecutive UC patients who received intravenous CsA for an acute refractory UC were included when they had endoscopic assessments with biopsies at entry and, at CsA interruption in responders. Mucosal healing (MH) was defined by Mayo endoscopic subscore ≤1 and, histologic response (HR) by the absence of basal plasmocytosis or a Geboes score Results Among 21 patients who responded to CsA, MH was achieved in 81%. Survival rates without relapse at 2 years were 79% and 25% in patients with MH and without MH, respectively (p = 0.04). HR was observed in 84% of patients according to basal plasmocytosis and in 68% according to Geboes score. Multivariate analysis revealed that a Mayo endoscopic subscore of 0 was the only prognostic factor associated with absence of relapse (RR = 12; 95%CI: 1.05–136.79). Conclusion CsA provides MH and HR in most of UC patients responding to this drug. As suggested with other UC treatments, a complete MH with CsA has a good prognostic value.

International audience; Objectives: High-resolution manometry (HRM) might be superior to conventional manometry (CM) to diagnose esophageal motility disorders. We aimed to compare the diagnosis performed with HRM and CM and confirmed at 6 months in a multicenter randomized trial.Methods: Patients with unexplained dysphagia were randomized to undergo either CM or HRM. Motility disorders were diagnosed using the Castell and Spechler classification for CM and the Chicago classification for HRM. Diagnosis confirmation was based on clinical outcome and response to treatment after 6-month follow-up. The initial diagnosis and percentage of confirmed diagnoses were compared between the two arms (CM and HRM).Results: In total, 247 patients were randomized and 245 analyzed: 122 in the CM arm and 123 in the HRM arm. A manometric diagnosis was more frequently initially achieved with HRM than with CM (97% vs. 84%;P

Background & Aims: We compared the ability of laparoscopic antireflux surgery (LARS) and esomeprazole to control esophageal acid exposure, over a 5-year period, in patients with chronic gastroesophageal reflux disease (GERD). We also studied whether intraesophageal and intragastric pH parameters off and on therapy were associated with long-term outcomes. Methods: We analyzed data from a prospective, randomized, open-label trial comparing the efficacy and safety of LARS vs esomeprazole (20 or 40 mg/d) over 5 years in patients with chronic GERD. Ambulatory intraesophageal and intragastric 24-hour pH monitoring data were compared between groups before LARS or the start of esomeprazole treatment, and 6 months and 5 years afterward. A secondary aim was to evaluate the association between baseline and 6-month pH parameters and esomeprazole dose escalation, reappearance of GERD symptoms, and treatment failure over 5 years in patients receiving LARS or esomeprazole. Results: In the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P

Approximately 20-30% of patients with gastro-esophageal reflux symptoms report inadequate symptom relief while on proton-pump inhibitor therapy. The mechanisms involved are failure of the antireflux barrier (transient lower esophageal sphincter relaxations), high proximal extent of the refluxate, esophageal hypersensitivity and impaired mucosal integrity. Persisting acid or nonacid reflux can be demonstrated in 40-50% of cases, suggesting that there is room for antireflux therapy in these patients. New antireflux compounds have been shown to decrease the occurrence of transient lower esophageal sphincter relaxations. The most promising classes of compounds are GABA type B agonists and metabotropic glutamate receptor 5 antagonists, which can reduce both reflux episodes and symptoms, but the development of these compounds has been abandoned for either safety issues or lack of efficacy. Esophageal hypersensitivity and impaired mucosal integrity may prove to be relevant therapeutic targets in the future.