Analysis of Postprandial Symptom Patterns in Subgroups of Patients With Rome III or Rome IV Functional Dyspepsia.

BACKGROUND & AIMS: Among patients with functional dyspepsia (FD), there is overlap in symptoms between those in the Rome III subgroups of postprandial distress syndrome (PDS) and those with epigastric pain syndrome (EPS). The Rome IV consensus proposed to incorporate all patients with postprandial symptoms into the PDS group. We aimed to evaluate the assessment of meal-related dyspepsia symptoms in patients with FD according to the Rome III vs Rome IV subdivisions. METHODS: Consecutive patients with FD referred for a gastric emptying test (n = 96) were asked to fill out the Rome III gastroduodenal questionnaire, with questions on meal-related occurrence. Study participants underwent a gastric emptying breath test, during which the intensity of dyspeptic symptoms (fullness, bloating, belching, nausea, epigastric pain, and burning) was scored before and up to 4 hours after a meal. We analyzed the association between the Rome subdivision and symptom severity and pattern during the breath test. RESULTS: According to Rome III, 10% had EPS alone, 29% PDS alone, and 61% overlapping EPS and PDS. The frequency of the symptoms reported in the Rome questionnaire associated with the intensity of the symptoms during the breath test in the PDS group and in the groups with PDS and EPS overlap, but not in the group with EPS. We adapted the definition of the PDS subgroup to include patients with meal-related non-PDS symptoms (Rome IV); this reduced the proportion of patients with overlap of EPS and PDS symptoms from 61% to 18% and in this group the association of symptoms with the meal was reduced. CONCLUSIONS: In an analysis of patients with FD, a meal induced or exacerbated symptoms in most patients. The Rome IV criteria for PDS reduce the proportions categorized as having both PDS and EPS and identify a patient group whose symptoms are associated with the meals. University hospital of Leuven study no: S55426.

The 2018 ISDE achalasia guidelines.

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.

Pathophysiological Abnormalities in Functional Dyspepsia Subgroups According to the Rome III Criteria.

OBJECTIVES: The Rome III criteria proposed to subdivide functional dyspepsia (FD) into a postprandial distress syndrome (PDS) group, characterized by the presence of postprandial fullness and/or early satiety, and an epigastric pain syndrome (EPS) group, characterized by the presence of epigastric pain and/or epigastric burning. It has been suggested that different pathophysiological mechanisms underlie the symptom presentations in these subgroups that might determine treatment choices. The aim of this study was to investigate the prevalence of gastric sensorimotor dysfunction in the PDS, EPS, and overlap groups and to evaluate potential differential associations with dyspeptic symptom scores. METHODS: Consecutive FD patients fulfilling Rome III criteria were recruited and they scored frequency of dyspeptic symptoms (postprandial fullness, early satiety, nausea, bloating, epigastric pain, and epigastric burning) over the past 3 months (0-5; 1=once a month or less, 2=two or three times a month, 3=once a week, 4=several times a week, 5=every day). The cumulative symptom score was calculated by adding up the score of these dyspeptic symptoms. Based on these symptom scores, the patients were subdivided into subgroups according to the Rome III consensus: (i) PDS, characterized by postprandial fullness and/or early satiety at least several times a week, (ii) EPS, characterized by epigastric pain and/or epigastric burning at least once a week, and (iii) overlap, fulfilling the criteria for both PDS and EPS. Gastric sensitivity and gastric accommodation were measured using barostat testing, and solid gastric emptying was determined using the [14C]octanoate breath test. RESULTS: A total of 560 FD patients (165 men, age 41.8±0.7 years) were classified into PDS (n=131), EPS (n=50), and overlap (n=379) groups. The prevalence of gastric hypersensitivity, impaired gastric accommodation, and delayed gastric emptying were 37%, 37%, and 23%, respectively, without any differential distribution in Rome III subgroups (P=0.16, P=0.27, and P=0.39 respectively). Comparing the physiological parameters for these gastric sensorimotor functions, there was only a significant difference in the gastric half emptying time between subgroups, with the overlap group having a higher t1/2 (P<0.05) compared with the EPS group. In the overlap group, gastric hypersensitivity was associated with the severity of PDS symptoms (P=0.03), EPS symptoms (P=0.02), and the cumulative symptom score (P=0.02), whereas delayed gastric emptying was associated with nausea (P=0.02) and the cumulative symptom score (P=0.02). CONCLUSIONS: Except for gastric emptying in the overlap group, FD subgroups as defined by the Rome III criteria are not differentially associated with putative pathophysiological mechanisms. These observations question the utility of this classification for guiding therapeutic choices in clinical practice.

Motilin-induced gastric contractions signal hunger in man.

RATIONALE: Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated by motilin. OBJECTIVES: To study the relationship between hunger and MMC phases (I-III), focusing on spontaneous and pharmacologically induced phase III and the correlation with plasma motilin and ghrelin levels. The role of phase III was also studied in the return of hunger after a meal in healthy individuals and in patients with loss of appetite. FINDINGS: In fasting healthy volunteers, mean hunger ratings during a gastric (62.5±7.5) but not a duodenal (40.4±5.4) phase III were higher (p<0.0005) than during phase I (27.4±4.7) and phase II (37±4.5). The motilin agonist erythromycin, but not the cholinesterase inhibitor neostigmine, induced a premature gastric phase III, which coincided with an increase in hunger scores from 29.2±7 to 61.7±8. The somatostatin analogue octreotide induced a premature intestinal phase III without a rise in hunger scores. Hunger ratings significantly correlated (ß=0.05; p=0.01) with motilin plasma levels, and this relationship was lost after erythromycin administration. Motilin, but not ghrelin administration, induced a premature gastric phase III and a rise in hunger scores. In contrast to octreotide, postprandial administration of erythromycin induced a premature gastric phase III accompanied by an early rise in hunger ratings. In patients with unexplained loss of appetite, gastric phase III was absent and hunger ratings were lower. CONCLUSIONS: Motilin-induced gastric phase III is a hunger signal from GIT in man.

Avoiding the use of long-term parenteral support in patients without intestinal failure: A position paper from the European Society of Clinical Nutrition & Metabolism, the European Society of Neurogastroenterology and Motility and the Rome Foundation for Disorders of Gut-Brain Interaction.

The role of long-term parenteral support in patients with underlying benign conditions who do not have intestinal failure (IF) is contentious, not least since there are clear benefits in utilising the oral or enteral route for nutritional support. Furthermore, the risks of long-term home parenteral nutrition (HPN) are significant, with significant impacts on morbidity and mortality. There has, however, been a recent upsurge of the use of HPN in patients with conditions such as gastro-intestinal neuromuscular disorders, opioid bowel dysfunction, disorders of gut-brain interaction and possibly eating disorders, who do not have IF. As a result, the European Society of Clinical Nutrition and Metabolism (ESPEN), the European Society of Neuro-gastroenterology and Motility (ESNM) and the Rome Foundation for Disorders of Gut Brain Interaction felt that a position statement is required to clarify - and hopefully reduce the potential for harm associated with - the use of long-term parenteral support in patients without IF. Consensus opinion is that HPN should not be prescribed for patients without IF, where the oral and/or enteral route can be utilised. On the rare occasions that PN commencement is required to treat life-threatening malnutrition in conditions such as those listed above, it should only be prescribed for a time-limited period to achieve nutritional safety, while the wider multi-disciplinary team focus on more appropriate biopsychosocial holistic and rehabilitative approaches to manage the patient's primary underlying condition.

Avoiding the use of long-term parenteral support in patients without intestinal failure: A position paper from the European Society of Clinical Nutrition & Metabolism, the European Society of Neurogastroenterology and Motility and the Rome Foundation for Disorders of Gut-Brain Interaction.

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Non-esophageal eosinophilic gastrointestinal diseases: a narrative review.

Eosinophilic gastrointestinal disorders are a group of rare diseases characterized by the infiltration of eosinophils in the gastrointestinal wall in a greater amount than in homeostatic conditions. 'Non-esophageal eosinophilic gastrointestinal disorders' is the umbrella term for all eosinophilic gastrointestinal disorders outside of the well known eosinophilic esophagitis. This includes eosinophilic gastritis, eosinophilic enteritis and eosinophilic colitis. The clinical presentation is atypical and not very different for the three disorders. The depth of infiltration has a bigger influence on the presenting symptoms than the disease location. Although the frequency of diagnosis and research in this subject is increasing over time, non-esophageal eosinophilic disorders are rare and high quality evidence is limited to date. In this narrative review, we provide an overview of the latest insights in the pathophysiology, diagnostic approach and available treatment options. Transcriptome studies have found the pathogenesis to be T helper type 2 driven. Various laboratory findings can be used to trigger raised suspicion and investigation with endoscopy. As the endoscopic appearance of the mucosa is normal in most cases, multiple biopsies in each segment are needed to quantify the amount of eosinophils in the tissue. Eosinophilic cut-offs for diagnosis are a controversial topic and a consensus is still lacking. A recently developed tissue based diagnostic platform which measures differentially expressed genes might be available in the future to classify patients with intermediate eosinophilic tissue levels under the cut-off. For the treatment, corticosteroids are still the cornerstone of treatment but promising research suggests a role of biologicals, such as Lirentelimab (anti-siglec 8) in particular.

Novel corticosteroid formulations in the treatment of eosinophilic esophagitis: what is the evidence?

Background and study aims: Eosinophilic esophagitis (EoE) is a food allergen-induced disease of the esophagus. Chronic, eosinophil-predominant inflammation eventually leads to fibrosis, esophageal dysfunction and severe morbidity. Swallowed topical corticosteroids (STCs) are a mainstay of anti-inflammatory therapy in the treatment of active EoE. Data on the efficacy of novel corticosteroid formulations, developed specifically for esophageal delivery, have recently become available. Methods: A comprehensive review was performed aiming to summarize evidence on the role of STCs in the treatment of EoE. Two biomedical bibliographic databases (PubMED, EMBASE) were searched for articles providing original information on the efficacy and safety of STCs in adult EoE patients. Results: Budesonide orodispersible tablet (BOT) and budesonide oral suspension (BOS) both surpassed placebo formulations regarding the efficacy of inducing and maintaining histologic, symptomatic and endoscopic remission. Overall, BOT displayed the highest grade of efficacy with clinico-histologic remission rates up to 75% after 1 year. Fluticasone propionate (APT-1011) achieved and maintained histologic and endoscopic responses in the majority of patients, whereas only a positive trend was demonstrated for symptomatic improvement. Mometasone and ciclesonide were studied in a limited number of smaller-scale trials and placebo-controlled data are required to substantiate the promising findings. All STCs displayed a similar side effects profile and were generally considered safe and well-tolerated. Conclusions: Current evidence supports long-term treatment with novel corticosteroid formulations, challenging the established treatment paradigm of EoE. BOT appears to be the most effective steroid therapy, although head-to-head comparative trials between STCs are needed.

Neuromodulating agents in functional dyspepsia: a comprehensive review.

Background and study aims: Functional dyspepsia is a common chronic condition with upper abdominal symptoms in the absence of an organic cause. The first line treatment consists of protonpomp inhibition or Helicobacter pylori eradication. However, this approach often does not provide enough symptom relief. Neuromodulating agents are commonly used in clinical practice but only tricyclic antidepressant (TCAs) are mentioned in European and American and Canadian guidelines. Methods: We performed a comprehensive review of the literature in Pubmed for full-text randomized controlled trials in English with adult participants (>18 years) who met the Rome II, III or IV criteria or were diagnosed by a physician with a negative upper endoscopy and that compared a neuromodulating agent with placebo. Results: The search strategy identified 386 articles of which 14 articles met the eligibility criteria. TCAs like amitriptyline and imipramine have been shown to be effective in the treatment of functional dyspepsia whereas other neuromodulating agents like tetracyclic antidepressants, levosulpiride and anxiolytics might be beneficial but conclusive evidence is lacking. serotonin and noradrenaline reuptake inhibitors (SNRI) and selective serotonin reuptake inhibitors (SSRI) have not shown benefit in patients with functional dyspepsia. Conclusion: Selected neuromodulators have an established efficacy in functional dyspepsia. The best supporting evidence is available for TCAs with a potential role for tetracyclic antidepressants, levosulpiride and anxiolytics.

Dumping syndrome after bariatric surgery: prevalence, pathophysiology and role in weight reduction - a systematic review.

Background: Dumping syndrome is a frequent and wellknown adverse event after bariatric surgery and covers a dynamic spectrum of early and late dumping. Accelerated gastric emptying is generally considered to be the cause of gastrointestinal and vasomotor complaints. However, there is much uncertainty regarding the exact pathophysiology of dumping. It has been speculated that the syndrome is a desired consequence of bariatric surgery and contributes to more efficient weight loss, but supporting data are scarce. Methods: A systematic search was conducted in PubMed in July-August 2021. The prevalence of dumping after the most frequently performed bariatric procedures was analyzed, as well as underlying pathophysiology and its role in weight reduction. Results: Roux-en-Y gastric bypass (RYGB) is associated with the highest postoperative prevalence of dumping. The fast transit induces neurohumoral changes which contribute to an imbalance between postprandial glucose and insulin levels, resulting in hypoglycemia which is the hallmark of late dumping. Early dumping can, when received in a positive way, become a tool to maintain a strict dietary pattern, but no significant relationship to the degree of weight loss has been shown. However, late dumping is detrimental and promotes overall higher caloric intake. Conclusion: Dumping syndrome is common after bariatric surgery, especially after RYGB. The pathophysiology is complex and ambiguous. Currently available data do not support dumping as a necessary condition to induce weight loss after bariatric surgery.

Review article: Functional dyspepsia-a gastric disorder, a duodenal disorder or a combination of both?

BACKGROUND: Functional dyspepsia (FD) is one of the most frequent conditions in gastroenterological outpatient health care. Most recent research in FD has shifted its focus to duodenal pathophysiological mechanisms, although current treatments still focus mainly the stomach. AIM: The aim of the study was to provide a comprehensive overview of the pathophysiology of FD focusing on a paradigm shift from gastric towards duodenal mechanisms. METHODS: We conducted a literature search in PubMed for studies describing mechanisms that could possibly cause FD. RESULTS: The pathophysiology of FD remains incompletely understood. Recent studies show that duodenal factors such as acid, bile salt exposure and eosinophil and mast cell activation correlate with symptom pattern and burden and can be associated with gastric sensorimotor dysfunction. The evolving data identify the duodenum an interesting target for new therapeutic approaches. Furthermore, the current first-line treatment, that is proton pump inhibitors, reduces duodenal low-grade inflammation and FD symptoms. CONCLUSION: Future research for the treatment of FD should focus on the inhibition of duodenal mast cell activation, eosinophilia and loss of mucosal integrity.

Chronic intestinal pseudo-obstruction: a case report with review of the literature and practical guidance for the clinician.

Chronic Intestinal Pseudo-obstruction (CIPO) is a rare but debilitating and severe form of gastrointestinal dysmotility. The diagnosis is often made very late in the disease course due to its rarity and complexity. Treatment is mainly supportive, as there is no definitive cure. Pharmacologic therapy comprises prokinetics, antibiotics for bacterial overgrowth and pain management. Pain can also be alleviated with intestinal decompression in selected cases. Beside the pharmacologic therapy, nutrition and fluid replacement play a key role. Rarely, intestinal transplantation is necessary in patients with CIPO and intestinal failure. In this review, we describe an advanced CIPO case and provide an update of the clinical and diagnostic features and current management strategies. The goal of our review is to raise awareness around CIPO and to give practical guidance for the clinician.

Belgian consensus on irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice. METHODS: A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement. RESULTS: Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged. CONCLUSIONS: A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.

Effect of obesity on gastrointestinal transit, pressure and pH using a wireless motility capsule.

BACKGROUND: Despite the increasing prevalence and medical burden of obesity, the understanding of gastrointestinal physiology in obesity is scarce, which hampers drug development. AIM: To investigate the effect of obesity and food intake on gastrointestinal transit, pressure and pH. MATERIAL AND METHODS: An exploratory cross-sectional study using a wireless motility capsule (SmartPill©) was performed in 11 participants with obesity and 11 age- and gender-matched participants with normal weight (group) in fasted and fed state (visit). During the first visit, the capsule was ingested after an overnight fast. During a second visit, the capsule was ingested after a nutritional drink to simulate fed state. Linear mixed models were constructed to compare segmental gastrointestinal transit, pressure and pH between groups (obesity or control) and within every group (fasted or fed). RESULTS: Food intake slowed gastric emptying in both groups (both P < 0.0001), though food-induced gastric contractility was higher in participants with obesity compared to controls (P = 0.02). In the small intestine, a higher contractility (P = 0.001), shorter transit (P = 0.04) and lower median pH (P = 0.002) was observed in participants with obesity compared to controls. No differences were observed for colonic measurements. CONCLUSION: Obesity has a profound impact on gastrointestinal physiology, which should be taken into account for drug development.

Intralesional steroid injections in addition to endoscopic dilation in benign refractory esophageal strictures : a systematic review.

BACKGROUND AND STUDY AIMS: Benign esophageal strictures are primarily treated with dilation therapy, but strictures can recur or can be unresponsive, requiring additional or repeated treatment. This study investigates the efficacy and safety of intralesional steroid injections in addition to dilation in comparison to dilation alone in patients with benign refractory or recurrent esophageal strictures. METHODS: A systematic search was carried out in PubMed, using the search terms "Esophageal Stenosis"[Mesh] AND "Injections, Intralesional"[Mesh]. In addition, the reference list of all selected articles was searched manually for other relevant articles. All clinical trials and case series were considered. RESULTS: This systematic review included four randomized controlled trials, six case series and two cohort studies, comprising 341 patients with benign esophageal strictures of different etiologies. A benefit of adding intralesional steroid injections to dilation in reducing the need for repeat dilation was seen in the subgroups of peptic, radiation-induced and corrosive strictures. Results were inconsistent for anastomotic strictures and too limited for strictures due to eosinophilic esophagitis, sclerotherapy or pill esophagitis. Complications were rare and of limited severity. CONCLUSION: Endoscopic dilation remains the first-line treatment, since its efficacy and safety are mostly satisfactory. In recurrent or refractory strictures, intralesional steroid injections are advised in peptic strictures and can be considered in radiation- induced, corrosive strictures and anastomotic strictures. It is recommended to restrict the steroid use to a maximum of three sessions and to consider alternative treatment if treatment effects remain insufficient.

Eosinophilic peak counts in eosinophilic esophagitis : a retrospective study.

BACKGROUND: The histologic diagnosis of eosinophilic esophagitis (EoE) is based on finding >15 eosinophils/high power field (HPF) on any level within the squamous epithelium of the esophagus. However, this criterion is based on a consensus statement, and controversy remains about the exact number of eosinophils/HPF needed to diagnose EoE. We aimed to determine eosinophilic peak counts in esophageal, gastric, and duodenal biopsies from suspected EoE patients, investigate the correlation between eosinophilic peak counts at different biopsy locations, and determine inter-observer and intra-observer reliability in reporting eosinophilic peak counts. METHODS: We selected 103 suspected EoE patients, who underwent an endoscopic procedure between June 1, 2010 and July 15, 2017. Eosinophilic peak counts in 1 HPF were obtained by a medical student and an experienced gastrointestinal pathologist. RESULTS: Eosinophilic peak counts in suspected EoE patients are highly variable (esophagus : IQR 66-178, median 110 ; stomach : IQR 2-10, median 3 ; duodenum : IQR 16-44, median 25). No significant correlation was found between eosinophilic peak counts at different biopsy locations. The inter-observer and intra-observer correlation for reporting eosinophilic peak counts was in the nearperfect range (ρ ranged from 0.93 to 0.99, P<0.0001). CONCLUSIONS: Our data suggest that the accuracy of determining eosinophilic peak counts is not influenced by the pathologist's experience. Therefore, variability in reporting eosinophilic peak counts is unlikely to influence the diagnostic accuracy of EoE. To further improve diagnostic accuracy, investigation of other histologic features observed in EoE is needed.

A single-center audit of the indications and clinical impact of prolonged ambulatory small intestinal manometry.

BACKGROUND: Small bowel manometry is a diagnostic test available only in a few specialized referral centers. Its exact place in the management of refractory symptoms is controversial. METHODS: The records of all patients who underwent 24-hour ambulatory duodenojejunal manometry over a 6-year period were retrospectively reviewed. We studied the clinical indications for small bowel manometry, and reviewed the impact of manometric findings on the clinical outcome. One hundred and forty-six studies were performed in 137 patients (46M, 91F) with a mean age of 44.9 ± 15.7 years. Mean follow-up duration was 15.1 ± 22.6 months. Appropriate endoscopic, radiological and gastric scintigraphy studies were performed in all patients prior to small bowel manometry. Criteria for abnormal motor activity were based on Bharucha's classification. KEY RESULTS: The indications for small bowel manometry were chronic abdominal pain (n = 43), slow-transit constipation (n = 17), refractory gastroparesis (n = 16), chronic diarrhea (n = 7), recurrent episodes of subocclusion (n = 16), postsurgical evaluation (n = 36), suspicion of gut involvement in systemic disease (n = 9), and unexplained nausea (n = 2). The most common finding was a normal 24-hour ambulatory small bowel manometry (n = 113). Thirty-three studies yielded abnormal findings which included extrinsic neuropathy (n = 6), intrinsic neuropathy (n = 18), intestinal myopathy (n = 2), and subocclusion (n = 7). Ambulatory small bowel manometry excluded a generalized motility disorder in 77% and had a significant impact on the subsequent clinical course in 23%. CONCLUSIONS & INFERENCES: Ambulatory small bowel manometry is a useful and safe diagnostic tool to complement traditional investigative modalities in patients with severe unexplained abdominal symptoms.