ACHALASIA TREATMENT IMPROVES SPECIFIC SYMPTOMS AND QUALITY OF LIFE: VALIDATION OF AN ACHALASIA SPECIFIC QUALITY OF LIFE QUESTIONNAIRE

Background and aim: Therapies for achalasia aim to patients’ symptom relief, but they affect patient’s quality of life (QoL), too. An ad hoc question- naire evaluating both achalasia-related symptoms and disease related QoL is lacking. Aim: To validate a disease specific QoL questionnaire in perspectively evaluated Italian achalasia patients. Material and methods: 22 consecutive achalasia patients (4 men, age range 19–86 years) were included in the study. At baseline a structured question- naire was used to evaluate both esophageal symptoms and disease specific QoL. Questionnaire graded achalasia-related symptoms severity (dysphagia for solids and liquids, food regurgitation, chest pain, nocturnal cough) from 0 to 3, based on their impact on daily activities. Also a disease specific QoL was evaluated by a self administred questionnaire, the AE-18, that investigated four domains (physical, psychological and social functioning, and sleep dis- turbance). Scores for each item range from 1 (“always”) to 5 (“never”); higher scores corresponding to better quality of life. All patients were questioned before, 1 and 6 months after a specific t reatment regimen, that according to patients clinical status consisted in pneumatic dilation, botulinum toxin injection or surgical myotomy. Results: Patients within each specific treatment groups were the following (3/22 surgical myotomy, 14/22 pneumatic dilation and 5/22 Botox injections, respectively. In the table are reported the baseline demographics and achalasia- related symptoms’ severity and QoL (data are expressed as mean ± SD) within each treatments group. Table 1 Surgery group Dilation group Botox group p Age at diagnosis 42.3 ± 6.5 42.3 ± 13 81.8 ± 4.8 < 0.001 Age at onset of symptoms 39.3 ± 7.5 40.3 ± 12.4 80.8 ± 5.6 < 0.001 Dysphagia for solids 2.7 ± 0.6 2.2 ± 0.7 2.2 ± 0.5 0.5 Dysphagia for liquids 2.0 ± 1.0 2.1 ± 0.7 2.2 ± 0.5 0.9 Regurgitation of undigested food 1.0 ± 1.7 0.7 ± 0.8 0.6 ± 1.3 0.8 Chest pain 0.7 ± 1.1 1.1 ± 1.1 1.0 ± 1.4 0.8 Nocturnal cough 1.3 ± 1.5 1.3 ± 1.2 1.0 ± 1.4 0.9 AE-18 total score 54 ± 14 53 ± 12 53 ± 11 0.9 At both 1 and 6 months of the follow-up, the severity mean scores of dysphagia achalasia-related symptoms severity were significantly reduced compared to baseline (p < 0.05). Similarly, the AE-18 total score was significantly improved (p < 0.001). Conclusions: We showed that therapy-induced improvement of achalasia- related symptoms correlate with a significant improvement of patients quality of life as assessed by a specific questionnaire

Predictors of abdominal pain severity in patients with constipation-prevalent irritable bowel syndrome

Symptoms of irritable bowel syndrome (IBS) have been associated to altered colonic motility and sensation. Smoking affects pain perception and is a risk factor in the development of post-infectious IBS, but its effect on abdominal pain and colonic transit remains to be elucidated in IBS. Forty patients with IBS-C and 28 with IBS-M were selected based on Rome IV criteria. Colonic transit time was studied and smoking habit was recorded. Presence of mild or severe abdominal pain and the prevalent pain characteristics (diffuse or localized, chronic or acute, with cramps or gradually distending) were recorded. Data were analyzed by univariate and stepwise multiple logistic regression analysis to verify the risk association between pain and all other variables. IBS-C patients had a longer transit time in the right colon and scored more chronic pain than IBS-M patients. When severity of abdominal pain was used as discriminating factor, a significant number of subjects reporting severe pain were males and smokers (16/30 vs. 4/38 and 20/30 vs. 4/38, both ƿ &lt;0.001). Multivariate analysis confirmed that smoking was an independent factor associated with severe abdominal pain (OR 14.3, CI 2-99, p=0.007). Smoking was not associated with colonic transit times and colonic transit was not associated with IBS symptoms' severity (both ƿ =N.S.) Smoking was the only factor independently associated with severe abdominal pain. As smoking does not seem to affect colonic transit time, we suggest that smoking may influence visceral perception and symptoms severity in IBS patients

Sleeve Gastrectomy-Induced Body Mass Index Reduction Increases the Intensity of Taste Perception’s and Reduces Bitter-Induced Pleasantness in Severe Obesity

Background: The sense of taste is involved in food behavior and may drive food choices, likely contributing to obesity. Differences in taste preferences have been reported in normal-weight as compared to obese subjects. Changes in taste perception with an increased sweet-induced sensitivity have been reported in surgically treated obese patients, but data regarding the perception of basic tastes yielded conflicting results. We aimed to evaluate basic taste identification, induced perception, and pleasantness in normal-weight controls and obese subjects before and after bariatric surgery. Methods: Severe obese and matched normal weight subjects underwent a standardized spit test to evaluate sweet, bitter, salty, umami, and sour taste identification, induced perception, and pleasant-ness. A subset of obese subjects were also studied before and 12 months after sleeve gastrectomy. Results: No significant differences in basic taste-induced perceptions were observed, although a higher number of controls correctly identified umami than did obese subjects. Sleeve-gastrectomy-induced weight loss did not affect the overall ability to correctly identify basic tastes but was associated with a significant increase in taste intensities, with higher scores for sour and bitter, and a significantly reduced bitter-induced pleasantness. Conclusions: The perception of basic tastes is similar in normal-weight and severely obese subjects. Sleeve-gastrectomy-induced weight loss significantly increases basic taste-induced intensity, and selectively reduces bitter-related pleasantness without affecting the ability to identify the tastes. Our findings reveal that taste perception is influenced by body mass index changes, likely supporting the hypothesis that centrally mediated mechanisms modulate taste perception in severe obesity

Gastric determinants of maximum satiety induced by standardized solid and liquid meal. An MRI study in non obese healthy subjects.

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<0.01; 31±17 p<0.01). However, total, proximal and distal gastric volume were not different between the two meals (SM: 657±186, 110±40, 546±173 vs LM: 651±299, 143±64, 507±283). Correlation analysis between total and distal gastric volumes and kcal at MS revealed a more strong and significant correlation during LM (r=0.98, p<0.001; r=0.95, p<0.001) compared to SM (r=0.76, p<0.01; r=0.78, p<0.01). No correlations were found between proximal volumes and kcal at MS. Percentages of gastric retention at 120 min were significantly higher with SM than with LM in the distal stomach, but not in the proximal stomach (63±13 vs 38±14, p<0.01 and 14±5 vs 10±7 p=NS). In addition, a significant correlation between the percentage of gastric retention at 120min and MS was only observed by considering total and distal stomach with LM (r=0.73 and r=0.61, p<0.01, respectively). CONCLUSION: By using a non-invasive methodology we showed that a standardized SM is a reliable tool to assess maximum satiety in healthy subjects. The lack of correlation between proximal gastric volumes and Kcals ingested at maximum satiety is probably related to the different intragastric distribution and handling of the liquid and solid meal

Effects of oral supplementation with the symbiotic (bifidobacterium longum w11 + fos actilight) on IBS with constipation: a randomized, dose finding trial, versus fibers,

Background and aim: Irritable bowel syndrome (IBS) is characterized by disturbed intestinal motility and sensations. Modulation of intestinal microflora has the potential to target both the disturbances but, to date, few studies have evaluated the efficacy and safety of probiotic administration in IBS. The aim of this study was to evaluate the effect of a symbiotic preparation (Bifidobacterium longum W11 5 × 10 9 viable bacteria + fructooligosaccharide –FOS- 2.5 gr per sachet) in IBS patients with constipation. Material and methods: A total of 30 IBS patients with constipation (22 women, age 18-46 years) according to the Roma III criteria were en- rolled. Patients were randomized into 3 groups receiving 2 or 6 sachets of the symbiotic plus 5 g of partially hydrolyzed guar gum (PHGG), or 5 g of PHGG5 alone, respectively. A daily visual analog score-based questionnaire, investigating the severity of abdominal pain, bloating and the feeling of incomplete evacuation, was administered during 2 run-in weeks and 4 treatment weeks, respectively; also, the number of weekly evacuation and the laxative consumption were considered. At baseline and at the end of the treatment the Bristol scale, the colonic transit time and the SF-36 were also evaluated. Results: At the end of the study, none of the patients reported ad- verse effects. Regardless of the treatment there was no significant improvement of abdominal pain or feeling of incomplete evacuation. A significant reduction of bloating severity was observed in subjects receiving 2 sachets of the symbiotic (4 ± 2vs1.6 ± 1 mm, p=0.01) compared to those receiving 6 or fibers alone (3 ± 2vs2 ± 1and2 ± 1 vs 1.5 ± 1 mm, respectively p=NS). The treatment regimens were similarly and significantly effective in improving frequency of defecation, colonic transit time and the stool consistency, as measured by the Bristol scale, whereas no significant improvement of both mental and physical component of the SF-36 questionnaire was observed. Conclusions: Our data demonstrate the utility of symbiotics over fibres in improving the severity of abdominal bloating in patients with IBS with constipatio

COMORBIDITIES IN IDIOPATHIC ACHALASIA: A PHENOTYPIC APPROACH TO DRIVE GENETIC ASSOCIATION STUDIES?

Background and aim: There is evidence that idiopathic achalasia has a genetic background and a significant association with several genetic polymorphisms has been indeed described. A given genetic background may affect the phenotypic manifestations of the disease and may account for the presence of contemporary complex diseases. Our aim is to provide a proof of concept study to evaluate comorbidities in achalasia patients, in order to drive future genetic association studies. Material and methods: The study population consisted of 162 patients (69 males, mean age 55 ± 16 years) with proven clinical and instrumental diagnosis of idiopathic achalasia. Gender and age matched subjects selected from the outpatient clinic and referring of esophageal disorders other than achalasia, served as controls. All patients were investigated for the presence of comorbidities (autoimmune diseases, endocrinopathies, hematologic diseases and cardiopathies and neoplasms). Given the high incidence in the general population, type II diabetes, hyperlipidemia and blood hypertension were recorded too. Results: The overall prevalence of comorbidities was similar in achalasia and control patients (62% vs 57%, respectively). 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 (46 ± 21 vs. 49 ± 16 years, respectively, p=NS). Blood hypertension, cardiopathies, hyperlipidemia, endocrinological and autoimmune disorders were the most frequently observed comorbidities in achalasia and controls (20 vs 30%, 10 vs 7%, 17% vs 31%, 8% vs 17% and 8% vs 5%, respectively p=all NS). In addition hematological disorders and type II diabetes were similarly prevalent in the two groups. Conclusions: We showed for the first time the type and the frequency of comorbidities in a large series of achalasia patients and we showed that their prevalence is similar to that of a matched control population. Although larger epidemiological studies are needed to confirm our data, our results indicate that the putative genetic factors associated with achalasia are specific for this diseas

RISK FACTORS ASSOCIATED WITH UNDESIRED BMI INCREASE IN GERD PATIENTS

Background and aim: Obesity is a multifactorial disease and is recognized as a risk factor for gastrooesophageal reflux disease (GERD). Recent data showing that long term PPI therapy is associated with weight gain, indirectly suggest that GERD may, per se, affect body weight. We aimed to examine the contribution of factors other than GERD on body weight changes. Material and methods: We studied 184 consecutive patients (63 male, age 46 ± 13 years) with clinical and instrumental (endoscopy and 24h pHmetry) diagnosis of GERD. At baseline BMI was recorded and GERD symptoms were scored. Coexistence of diabetes, hypertriglyceridemia, hypertension and hypercholesterolemia were also recorded. All patients were treated with stan- dard dosage of PPIs for 6 weeks and advised on lifestyle modifications, but not on selective diet, or weight management, and followed up to 1 years. In case of symptoms recurrence, patients were also instructed to reintroduce PPIs therapy on an demand regimen. BMI, persistence of GERD symptoms and needing for PPI therapy were recorded at the follow-up. Data were analysed by considering the effect of all of the variables on BMI changes ( < or > 5% respect to baseline BMI) at the end of follow up. Patients were divided in normal weight, overweight or obese according to internationally accepted BMI values. Results: Averaged BMI values were unchanged at the end of the follow up (26 ± 5vs.26 ± 5). Similarly, patients with normal weight, overweight and obesity were respectively 37, 46 and 17% vs. 37, 44 and 19%. No significant differences in terms of demographic factors, persistence of GERD symptoms and needing of PPI therapy were found in patients with either BMI decrease or increase, respectively. When all variables were computed in a multivariate analysis, only pre-existing normal weight (OR 2.6, 95% CI 1-6.7, p=0.03) and diabetes (OR 5, 95%CI 1-18, p=0.007) were significantly associated to the risk of increased BMI. Conversely, only obesity (OR 5, 6%CI 1.7-19, p=0.005) was a risk factor associated with reduced BMI. Conclusions: Other factors rather than symptoms persistence and PPI therapy are associated with BMI changes in a population of GERD patients. The finding that baseline normal weight and diabetes are associated with undesired weight increase suggests an accurate screening to avoid BMI increase in this subset of GERD patients

Dyspeptic symptoms improvement in patients with non-erosive reflux disease is correlated with the degree of intragastric acid inhibition.

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, p<0.05), with the former having a longer intragastric acid suppression (78±2.6 vs. 65±5.4 %pH >3, p<0.05). Our findings confirm that functional dyspepsia may coexist in patients with non-erosive reflux disease. A four-week treatment with esomeprazole is effective in reducing dyspeptic symptoms in 60% of subjects with NERD. Furthermore, a better improvement of dyspeptic symptoms seems dependent on the extent of intragastric acid suppressio