Lorenzo Bertani

Association Between Baseline Impedance Values and Response Proton Pump Inhibitors in Patients With Heartburn

BACKGROUND & AIMS Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). METHODS In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. RESULTS FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. CONCLUSIONS Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for identification of patients who respond to PPIs but would be classified as having FH based on conventional impedance-pH measurements.

Proton pump inhibitor responders who are not confirmed as GERD patients with impedance and pH monitoring: who are they?

A short‐course of proton pump inhibitors (PPIs) is often used to confirm gastroesophageal reflux disease (GERD). However, some patients with PPI responsive heartburn do not seem to have evidence of GERD on impedance‐pH monitoring (MII‐pH). The aim of the study was to evaluate patients with reflux symptoms and a negative endoscopy, who well respond to PPIs with MII‐pH.

Esophageal testing: What we have so far

Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising.

Functional Heartburn Overlaps With Irritable Bowel Syndrome More Often than GERD

Objectives:We aimed to evaluate the prevalence of irritable bowel syndrome (IBS) in patients with typical reflux symptoms as distinguished into gastroesophageal reflux disease (GERD), hypersensitive esophagus (HE), and functional heartburn (FH) by means of endoscopy and multichannel intraluminal impedance (MII)-pH monitoring. The secondary aim was to detect pathophysiological and clinical differences between different sub-groups of patients with heartburn.Methods:Patients underwent a structured interview based on questionnaires for GERD, IBS, anxiety, and depression. Off-therapy upper-gastrointestinal (GI) endoscopy and 24 h MII-pH monitoring were performed in all cases. In patients with IBS, fecal calprotectin was measured and colonoscopy was scheduled for values >100 mg/kg to exclude organic disease. Multivariate logistic regression analysis was performed to identify independent risk factors for FH.Results:Of the 697 consecutive heartburn patients who entered the study, 454 (65%) had reflux-related heartburn (GERD+HE), whereas 243 (35%) had FH. IBS was found in 147/454 (33%) GERD/HE but in 187/243 (77%) FH patients (P<0.001). At multivariate analysis, IBS and anxiety were independent risk factors for FH in comparison with reflux-related heartburn (GERD+HE).Conclusions:IBS overlaps more frequently with FH than with GERD and HE, suggesting common pathways and treatment. HE showed intermediate characteristic between GERD and FH.

Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure

Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity.

657 Use of a Non-Invasive Pepsin Diagnostic Test to Detect GERD: Correlation With MII-pH Evaluation in a Series of Suspected NERD Patients. A Pilot Study

BACKGROUND: Presence of pepsin in bronchoalveolar lavage fluid, laryngeal biopsy and sputum may be a consequence of gastroesophageal reflux disease (GERD). A novel noninvasive test to detect it in saliva/sputum (PEP-Test) has been proposed to diagnose GERD. A correlation between PEP-Test and multichannel impedance pH monitoring (MII-pH) has never been performed. AIM: The aim was to evaluate the PEP-Test accuracy for the diagnosis of GERD in patients with reflux symptoms by means of MII-pH. PATIENTS ANDMETHODS: 35 patients with GER symptoms were studied. All patients with negative endoscopy underwent pathophysiological examinations, after wash-out from proton pump inhibitors. Samples of saliva/sputum were obtained by requesting the patient to cough up and spit into a tube containing 0.01 M citric acid within 15 minutes from experiencing reflux symptoms. Patients were grouped on the basis of MII-pH results as follows: True-NERD (increased acid exposure time, AET/reflux number); Hypersensitive Esophagus, HE (normal AET/reflux number, positive symptom association probability index, SAP); no-GERD patients (normal AET/reflux number, negative SAP). Roc curve was performed to obtain diagnostic accuracy of test. RESULTS: Male/Female was 18/17, mean age was 49.8 yrs, mean BMI was 24.9. The mean BMI was similar in three sub-groups. Nine patients were abitudinary smokers and five had a regular alimentary alcohol use. Eleven out of thirty-five patients presented hiatal hernia. No patients showed abnormal esophageal motility. MII-pH results showed: 16 True-NERD patients (median AET 9.5); 12 HE (median AET 3); 7 no-GERD (median AET 1.1). PEPTest was positive in 93.7% of True-NERD, in 58.3% of HE, and negative in 100% of noGERD patients. Accuracy of PEP-Test is reported in Table 1. CONCLUSIONS: PEP-Test is a simple, economic, reproducible, highly specific test to detect the presence of GERD. Accuracy PEP-Test

Effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota, short chain fatty acids, and immune activation in patients with irritable bowel syndrome: A pilot randomized clinical trial:

Background Evidence suggests a role of intestinal microbiota-host interactions in the pathophysiology and symptoms of irritable bowel syndrome (IBS). Objective The objective of this article is to assess the effects of Lactobacillus paracasei CNCM I-1572 on clinical and gut microbiota-related factors in IBS. Methods We conducted a multicenter, randomized, double-blind, cross-over, 18-week, placebo-controlled, pilot trial assessing the effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota composition, fecal short chain fatty acid (SCFA), immunoglobulin A, and cytokines in IBS. The intestinal microbial ecosystem was characterized by 16S rRNA gene profiling. Results Forty IBS patients were enrolled from five Italian centers. Lactobacillus paracasei CNCM I-1572 did not significantly improve IBS symptoms, including primary efficacy variables worst abdominal pain/discomfort and IBS degree of relief. Interestingly, Lactobacillus paracasei CNCM I-1572 induced a significant reduction in genus Ruminococcus, dominated by taxa related to Ruminococcus bromii and Ruminococcus callidus, a significant increase in the SCFAs acetate and butyrate, and a significant reduction in the pro-inflammatory cytokine interleukin-15. Conclusions This pilot study shows that Lactobacillus paracasei CNCM I-1572 is able to modulate gut microbiota structure/function and reduce immune activation in IBS. As no statistically significant effect on IBS-symptoms was found, further studies are necessary to determine the role of this probiotic in IBS. The study was registered at ClinicalTrials.gov registry under identifier NCT02371499.

Barrett's esophagus in 2016: From pathophysiology to treatment.

Esophageal complications caused by gastroesophageal reflux disease (GERD) include reflux esophagitis and Barretts esophagus (BE). BE is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). The carcinogenic sequence may progress through several steps, from normal esophageal mucosa through BE to EAC. A recent advent of functional esophageal testing (particularly multichannel intraluminal impedance and pH monitoring) has helped to improve our knowledge about GERD pathophysiology, including its complications. Those findings (when properly confirmed) might help to predict BE neoplastic progression. Over the last few decades, the incidence of EAC has continued to rise in Western populations. However, only a minority of BE patients develop EAC, opening the debate regarding the cost-effectiveness of current screening/surveillance strategies. Thus, major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC, which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs. Furthermore, the area of BE therapeutic management is rapidly evolving. Endoscopic eradication therapies have been shown to be effective, and new therapeutic options for BE and EAC have emerged. The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy. Moreover, we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE.

Obesity is a Risk Factor for Erosive Gastroesophageal Reflux Disease: Prospective Case-Control Study

Background and aim: An association between high body mass index (BMI) and gastroesophageal reflux disease (GERD) has been proposed but the relationship between the severity of obesity, the prevalence of symptoms and gravity of esophagitis is still unclear. Aim of this study was to evaluate the prevalence of symptomatic GERD and esophagitis in female obese subjects compared to a group of female with typical GERD symptoms. Material and methods: 193 obese women (Group A) scheduled for bariatric surgery and 193 normal weight female with typical GERD symptoms (Group B) were submitted to complete history (recording voluptuary habits) and validated questionnaire for symptomatic diagnosis of GERD (GIS: GERD Impact Scale). Each patient underwent upper GI endoscopy to evaluate the prevalence of erosive esophagitis. Erosive esophagitis was diagnosed according to Los Angeles Classification of esophagitis. Results: We enrolled 193 female patients in Group A and 193 patients in Group B. Mean age (± sd) was 48.6 ± 13.6 years in Group A and 51.4 ± 15.3 years in group B. Mean BMI was 43.6 ± 9.2 in group A and 23.6 ± 3.7 in Group B (P<0.001). The perception of GERD symptoms was higher in group B: the mean value of GIS was 1.72 when compared with 0.34 obtained in Group A (P<0.001). The mean value of score for typical GERD symptoms was 2.65 in group B and 0.85 in group A (P<0.001). All patients in Group B recorded at least one typical GERD symptom (heartburn and regurgitate) but only 26.9% of patients in Group A recorded these symptoms (P<0.001). Esophageal erosion were present in 97/193 (50.3%) in Group A and in 45/193 (23.3%) in Group B (P<0.001). Conclusions: We can conclude that the impact of erosive esophagitis in obese patients could be considered more severe than gravity and frequency of symptoms.

Fecal Clostridiales distribution and short-chain fatty acids reflect bowel habits in irritable bowel syndrome: Fecal microbial ecosystem of IBS subtypes

Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is classified according to bowel habits as IBS with constipation (IBS-C), with diarrhea (IBS-D), with alternating constipation and diarrhea (IBS-M), and unsubtyped (IBS-U). The mechanisms leading to the different IBS forms are mostly unknown. This study aims to evaluate whether specific fecal bacterial taxa and/or short-chain fatty acids (SCFAs) can be used to distinguish IBS subtypes and are relevant for explaining the clinical differences between IBS subcategories. We characterized five fecal samples collected at 4-weeks intervals from 40 IBS patients by 16S rRNA gene profiling and SCFA quantification. Finally, we investigated the potential correlations in IBS subtypes between the fecal microbial signatures and host physiological and clinical parameters. We found significant differences in the distribution of Clostridiales OTUs among IBS subtypes and reduced levels of SCFAs in IBS-C compared to IBS-U and IBS-D patients. Correlation analyses showed that the diverse representation of Clostridiales OTUs between IBS subtypes was associated with altered levels of SCFAs; furthermore, the same OTUs and SCFAs were associated with the fecal cytokine levels and stool consistency. Our results suggest that intestinal Clostridiales and SCFAs might serve as potential mechanistic biomarkers of IBS subtypes and represent therapeutic targets.