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.

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.

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.

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.

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.

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.