Search

SummaryBackgroundThere is evidence that idiopathic achalasia has an autoimmune component and a significant association with several autoimmune comorbidities has been described. However, data regarding the prevalence of autoimmune diseases in achalasia are not well established, and few studies have explored this association.ObjectiveOur primary aim was to prospectively investigate the type and frequency of autoimmune comorbidities in a large cohort of consecutive achalasia patients. Our secondary aim was to investigate the effects of autoimmune comorbidities on achalasia phenotype (clinical features and manometric pattern).MethodsThe study population consisted of 375 consecutive patients (215 females—median age 55 ± 17 years), referred at our tertiary referral center from January 2008 to January 2018, with clinical and instrumental (EGDS, barium esophagogram, and manometry) diagnosis of idiopathic achalasia. Gender- and age-matched subjects undergoing manometry and pH-impedance monitoring for typical gastroesophageal reflux (GERD) complaints served as controls. In all patients a detailed history taking was carried out, recording the presence and type of autoimmune comorbidities.ResultsThe overall prevalence of autoimmune comorbidities was two times higher in achalasia than in control patients (12.3 vs. 5%, respectively). The presence of comorbidities did not significantly affect disease’s phenotype, as the age of disease onset was similar in achalasia patients with and without comorbidities (50.13 ± 14.47 and 48.3 ± 18.71, respectively, P = NS).ConclusionsAlthough larger epidemiologic studies are needed to confirm our data, our findings likely suggest that achalasia has a complex multifactorial pathophysiology with an autoimmune component.

BACKGROUND: Gastric contribution to satiety has been mostly investigated by invasive methods and by the administration of liquid meals. Nonetheless, these conditions may alter the physiology of the stomach and do not reflect individual's alimentary habit, respectively. AIM: To study gastric determinant to satiety in a more physiological fashion by a non invasive method as MRI and by standardized solid (SM) and liquid (LM) meal. SUBJECTS AND METHODS: Ten healthy subjects (4 F; Age 22±3; BMI 23±1) underwent satiety tests by SM and LM on two separate occasions. Subjects were requested to maintain intake at regular rate (100 kcal/5 min). At five minute intervals, they scored their satiety using a graphic rating scale that combined verbal descriptors on a scale graded 0-5 (1=threshold, 5=maximum satiety). Kcal and time to reach maximum satiety (MS) were calculated. During the meal tests, a gastric 1.5 T MRI using a multi-receive parallel body-synergy-coil was performed. Three acquisitions were then recorded at baseline, maximum satiety and 120 min postprandially, in order to calculate total, proximal and distal gastric volumes at each time point. Also, residual volumes at 120 min were calculated and expressed as percentage respect to MS. Data are expressed as mean±SD. RESULTS: Kcals ingested and time to reach MS were significantly higher during SM (783±244 kcal; 44±14 min) than LM (630±353 p

Functional dyspepsia and non-erosive reflux disease (NERD) are highly prevalent functional diseases. In both the diseases symptoms overlap can be expected by chance alone, but recent data indicated that acid may be the common factor to explain symptoms generation. Indeed, esophageal acid perfusion has been recently associated with the onset of dyspeptic symptoms in healthy volunteers. Our aim was to study the effect of acid and its suppression, by PPI therapy, on NERD patients with dyspeptic symptoms. Hundred-twenty consecutive patients with reflux-associated symptoms were studied. Sixty-nine of them were selected because they were found to have non-erosive reflux disease during upper GI endoscopy and fulfilled the Rome criteria for functional dyspepsia. A standardized questionnaire, assessing the severity (effect on daily activities, from 0 to 3) of belching, abdominal bloating, early satiety, epigastric pain and burning, nausea, vomiting and postprandial fullness, and an esophagogastric 24hr pHmetry were performed before and at 4th week therapy with esomeprazole 20 mg bid. Intragastric acid inhibition was evaluated as the % of pH >3 and symptoms improvement was considered effective if a reduction of dyspepsia severity score (at least 50%) respect to baseline was obtained. Esophageal basal acid exposure (pH 4%) was pathological in 44 pts, whereas it was normal in 25. No significant difference was observed in the prevalence and the severity of individual dyspeptic symptoms. At baseline the intragastric % pH >3 was similar in subjects with normal and abnormal acid exposure (19±3.8 vs 18±4.5, p=NS). During esomeprazole therapy, reflux-associated symptoms improved in the majority of patients, but 7/69 patients had persistent pathological esophageal acid exposure. Overall PPI therapy significantly improved dyspeptic symptoms in 42/69 patients. Dyspepsia improvement was present in a higher number of patients with abnormal than in those with normal basal acid exposure (31/44 vs 11/25, respectively, p3, p

Background & Aims Acid hypersensitivity is claimed to be a symptomatic trigger in functional dyspepsia (FD); however, the neuroimmune pathway(s) and the mediators involved in this process have not been investigated systematically. Palmitoylethanolamide (PEA) is an endogenous compound, able to modulate nociception and inflammation, but its role in FD has not been assessed. Methods Duodenal biopsy specimens from FD and control subjects, and peroxisome proliferator-activated receptor-α (PPARα) null mice were cultured at a pH of 3.0 and 7.4. Mast cell (MC) number, the release of their mediators, and the expression of transient receptor potential vanilloid receptor (TRPV)1 and TRPV4, were evaluated. All measurements also were performed in the presence of a selective blocker of neuronal action potential (tetradotoxin). FD and control biopsy specimens in acidified medium also were incubated in the presence of different PEA concentrations, alone or combined with a selective PPARα or PPAR-γ antagonist. Results An acid-induced increase in MC density and the release of their mediators were observed in both dyspeptic patients and controls; however, this response was amplified significantly in FD. This effect was mediated by submucosal nerve fibers and up-regulation of TRPV1 and TRPV4 receptors because pretreatment with tetradotoxin significantly reduced MC infiltration. The acid-induced endogenous release of PEA was impaired in FD and its exogenous administration counteracts MC activation and TRPV up-regulation. Conclusions Duodenal acid exposure initiates a cascade of neuronal-mediated events culminating in MC activation and TRPV overexpression. These phenomena are consequences of an impaired release of endogenous PEA. PEA might be regarded as an attractive therapeutic strategy for the treatment of FD., Graphical abstract

Background: In gastroesophageal reflux disease (GORD) patients, coexistence of functional dyspepsia (FD) is known to be associated with poor response to proton pump inhibitors (PPIs), but the contribution of specific dyspepsia symptoms has not been systematically investigated yet. Objective: To characterize the impact of dyspepsia symptoms on PPIs response in GORD patients. Methods:. The enrolled subjects were 100 patients with diagnosis of GORD. All patients underwent a 24 hour pH-impedance test, while on PPIs-therapy. Patients were divided into two groups, refractory and responders, according to the persistence of GORD symptoms. A standardized questionnaire for FD was also administered to assess presence of dyspepsia symptoms. Results: In the subgroup of refractory patients FD was more prevalent than in responder ones, with postprandial fullness, nausea, vomiting, early satiation and epigastric pain being significantly prevalent in refractory GORD-patients. In the multivariate analysis only early satiation and vomiting were significantly associated with poor response to PPIs Conclusion: Coexistence of FD is associated with refractory-GORD. We showed that only early satiation and vomiting are risk factors for poor response to PPIs therapy. Our findings suggest that symptoms of early satiation and vomiting would help to identify the subset of PPIs-refractory GORD patients.

Background There is conflicting data on the effects of carbon dioxide contained in beverages on stomach functions. We aimed to verify the effect of a pre-meal administration of a 300 ml non-caloric carbonated beverage (B+CO2) compared to water or a beverage without CO2 (B-CO2), during a solid (SM) and a liquid meal (LM) on: a) gastric volume, b) caloric intake, c) ghrelin and cholecystokinin (CCK) release in healthy subjects. Methods After drinking the beverages (Water, B-CO2, B+CO2), ten healthy subjects (4 women, aged 22-30 years; BMI 23 ± 1) were asked to consume either an SM or an LM, at a constant rate (110 kcal/5 min). Total gastric volumes (TGV) were evaluated by Magnetic Resonance Imaging after drinking the beverage and at maximum satiety (MS). Total kcal intake at MS was evaluated. Ghrelin and CCK were measured by enzyme immunoassay until 120 min after the meal. Statistical calculations were carried out by paired T-test and analysis of variance (ANOVA). The data is expressed as mean ± SEM. Results TGV after B+CO2 consumption was significantly higher than after B-CO2 or water (p < 0.05), but at MS, it was no different either during the SM or the LM. Total kcal intake did not differ at MS after any of the beverages tested, with either the SM (Water: 783 ± 77 kcals; B-CO2: 837 ± 66; B+CO2: 774 ± 66) or the LM (630 ± 111; 585 ± 88; 588 ± 95). Area under curve of ghrelin was significantly (p < 0.05) lower (13.8 ± 3.3 ng/ml/min) during SM following B-CO2 compared to B+CO2 and water (26.2 ± 4.5; 27.1 ± 5.1). No significant differences were found for ghrelin during LM, and for CCK during both SM and LM after all beverages. Conclusions The increase in gastric volume following a 300 ml pre-meal carbonated beverage did not affect food intake whether a solid or liquid meal was given. The consistency of the meal and the carbonated beverage seemed to influence ghrelin release, but were unable, under our experimental conditions, to modify food intake in terms of quantity. Further studies are needed to verify if other food and beverage combinations are able to modify satiation.