The Effect of Dexlansoprazole on Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor-PPI) in resolving heartburn, reflux, and other symptoms and complications resulting from gastroesophageal reflux disease (GERD). The study followed PRISMA 2020 and was registered in PROSPERO (CRD42020206513). The search strategy used MeSH and free terms appropriately adapted for each database. Only randomized clinical trials (RCTs) were included. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the certainty of evidence was rated using GRADE. Ten RCTs were included. Dexlansoprazole outperformed the placebo and other PPIs in the resolution of heartburn and reflux symptoms in patients with GERD, with benefits during and after treatment, especially in those with moderate and severe symptoms. The meta-analyses indicated that dexlansoprazole at doses of 30 and 60 mg had more 24 h heartburn-free days and nights compared to the placebo medications; no difference was reported between dexlansoprazole at doses of 30 and 60 mg in heartburn-free nights. A low bias risk and a moderate certainty of evidence were observed. This review confirms the therapeutic effect of dexlansoprazole (placebo-controlled) and its improvements in GERD symptoms compared to another PPI. However, the interpretation of the results should be carried out cautiously due to the small number of included studies and other reported limitations.

Colorectal cancer chemotherapy: can sex-specific disparities impact on drug toxicities?

PURPOSE: Given the biological differences between females and males, sex-specific evaluations should be carried out to obtain better cancer prevention, diagnosis, and treatment strategies. To this purpose, our aim was to evaluate sex differences for toxicity in a cohort of colorectal cancer (CRC) patients undergoing chemotherapy. METHODS: We performed a retrospective study in 329 CRC patients. Differences between males and females were tested performing the Mann-Whitney U test or the Fisher exact test. Multivariate logistic regression models were computed to evaluate the association between sex and risk of chemotherapy agent-related toxicity. RESULTS: According association sex toxicity, significant differences were observed in the median number of episodes of nausea (p = 0.044), vomit (p = 0.007), heartburn (p = 0.022), thrombocytopenia (p = 0.005), mucositis (p = 0.024). Moreover, statistically significant differences between males and females were observed in the distribution of the highest toxicity grades of nausea (p = 0.024), heartburn (p = 0.016), and thrombocytopenia (p = 0.034). Females have an increased risk of vomit (p = 0.002), alopecia (p = 0.035), heartburn (p = 0.005), mucositis (p = 0.003), and lower risk for thrombocytopenia (p = 0.005). CONCLUSION: According to the association of sex chemotherapy agent-related toxicities, females resulted on average at a significant increased risk of more common adverse events (constipation, dysgeusia, alopecia, heartburn, vomit, asthenia, nausea, pain events, and mucositis). Sex-tailored CRC chemotherapy treatment is necessary to obtain efficacy avoiding toxicity, based on patients' biological and genetic characteristics, a vision that would change CRC setting, a stable disease but still orphan of a real tailored approach.

Gamma-aminobutyric acid receptor type B agonist baclofen inhibits acid-induced excitation of secondary peristalsis but not heartburn sensation.

BACKGROUND AND AIM: Acute esophageal acid infusion promotes distension-induced secondary peristalsis. The gamma-aminobutyric acid receptor type B (GABA-B) receptors activation inhibits secondary peristalsis. This study aimed to test the hypothesis whether acid excitation of secondary peristalsis can be influenced by baclofen. METHODS: Secondary peristalsis was performed with intra-esophageal slow and rapid air injections in 13 healthy subjects. Direct esophageal infusion of 0.1 N HCl following pretreatment with placebo or baclofen was randomly performed at least 1 week apart. Symptom intensity, distension thresholds, and peristaltic parameters were determined and compared between each study protocol. RESULTS: The intensity of heartburn symptom in response to esophageal acid infusion was significantly greater with baclofen than the placebo (P = 0.002). The threshold volume of secondary peristalsis during slow air injections in response to acid infusion was significantly greater with baclofen than the placebo (P = 0.001). Baclofen significantly increased the threshold volume of secondary peristalsis during rapid air injections in response to acid infusion (P = 0.001). The frequency of secondary peristalsis in response to acid infusion was significantly decreased by baclofen as compared with the placebo (P = 0.001). Baclofen significantly decreased peristaltic amplitudes in response to acid infusion during rapid air injections (P = 0.007). CONCLUSIONS: Gamma-aminobutyric acid receptor type B agonist baclofen inhibits acid excitation of secondary peristalsis in human esophagus, which is probably mediated by both muscular and mucosal mechanoreceptors. This work supports the evidence of potential involvement of GABA-B receptors in negative modulation of acid excitation of esophageal perception as well as secondary peristalsis.

The infusion of menthol into the esophagus evokes cold sensations in healthy subjects but induces heartburn in patients with gastroesophageal reflux disease (GERD).

Recent studies in animal models have reported that some afferent fibers innervating the esophagus express the cold receptor TRPM8. In the somatosensory system the stimulation of TRPM8 leads to cold sensations and in certain circumstances alleviates pain. It is therefore hypothesized in this paper that the esophageal infusion of the TRPM8 activator menthol evokes cold sensations from the esophagus and alleviates heartburn in humans. The esophageal infusion of menthol (3 mM, 20 min) evoked cold sensations in 11 of 12 healthy subjects. In striking contrast, the esophageal infusion of menthol evoked heartburn in 10 of 10 patients with gastroesophageal reflux disease (GERD). In healthy subjects the cold sensation evoked by menthol was perceived only as a minor discomfort as evaluated by the visual analog scale (VAS score 1.9 ± 0.3 on the scale 1-10). However, in patients with GERD the menthol-induced heartburn was perceived as painful (VAS score 5.6 ± 0.6, P < 0.01 compared to healthy subjects). It is concluded that the sensations evoked by esophageal infusion of menthol change from relatively nonpainful cold sensations in healthy subjects to painful heartburn sensations in patients with GERD. These qualitative and quantitative changes indicate substantial alterations in afferent signaling mediating sensations from the esophagus in patients with GERD.

[Effect of omeprazole on plasma concentration and adverse reactions of capecitabine in patients with colon cancer].

Objective: To investigate the effect of omeprazole on plasma concentration, efficacy and adverse reactions of capecitabine in patients with colon cancer. Methods: Seventy-two patients with colon cancer treated with capecitabine were analysed retrospective. The patients treated with capecitabine combined with omeprazole were identified as experimental group and the capecitabine treatment alone as control group.The differences of blood concentration and the side effects of capecitabine between these two groups were compared. Results: The plasma concentration of 5-Fluorouracilum in experimental group was (126.25±50.59) µg/ml, without significant difference of (123.09±56.70) µg/ml in control group (P=0.121). The incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and hand-foot syndrome in experimental group were 13.8%, 0%, 0% and 19.4%, respectively. In control group, the incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and the hand-foot syndrome were 11.1%, 0%, 0% and 19.4%, respectively, without significant difference of experimental group (P>0.05). The incidence of acid reflux and heartburn in the control group was 72.2%, significantly higher than 44.4% of the experimental group (P<0.05). The objective response rate (ORR) and progression-free survival time (PFS) in these two groups were 30.6% and 33.3%, and 8.0 month and 8.5 month, respectively, without significant difference (P>0.05). Conclusion: The intravenous omeprazole attenuates reflux and heartburn of colon cancer patients treated with capecitabine, without affecting its plasma concentration and side effects and has no impact on the PFS of these patients.

Impact of lubiprostone on gastric-emptying profile and the possible effect of concomitant domperidone in healthy adults
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BACKGROUND: Lubiprostone is effective for patients with chronic constipation. This agent sometimes causes upper gastrointestinal symptoms, such as nausea, which is one of the chief reasons for discontinuation. However, the etiology of and strategy against bothersome gastrointestinal symptoms of lubiprostone remain unclear. AIMS: The goal of this study was to investigate the influence of lubiprostone on the gastric-emptying profile of healthy adults. The effect of domperidone on gastric emptying and gastrointestinal symptoms after lubiprostone administration were also assessed. MATERIALS AND METHODS: 80 healthy male participants underwent 13C acetate breath testing to evaluate gastric emptying. The test meal comprised 200 kcal of a standard liquid nutrient. Each participant underwent 3 random breath tests with: 1) no premedication; 2) 24 µg of lubiprostone 30 minutes prior to the study; and 3) 24 µg of lubiprostone plus 10 mg of domperidone 30 minutes prior to the study. Gastrointestinal symptoms (heartburn, regurgitation, epigastric pain, fullness, distress feeling) during testing were evaluated using a 7-point scoring system. RESULTS: Gastric emptying was significantly delayed by the administration of lubiprostone. Among all 8 subjects, 4 reported heartburn after taking lubiprostone, whereas this symptom was not found when subjects received concomitant domperidone. However, gastric emptying showed little change between lubiprostone alone and lubiprostone plus domperidone. CONCLUSION: Lubiprostone delayed gastric emptying of liquid in healthy adults, which could be associated with the gastrointestinal symptoms caused by the agent. Domperidone seemed effective against such gastrointestinal symptoms after administration of lubiprostone. This effect seemed unrelated to gastric motility.
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Complications of botulinum toxin injections for treatment of esophageal motility disorders†.

In achalasia and spastic esophageal motility disorders, botulinum toxin (botox) injection is considered an effective and low-risk procedure for short-term symptom relief. It is mainly offered to medically high-risk patients. However, no analysis of risks of botox injections has been performed. To determine the incidence and risk factors of procedure-related complications after esophageal botox injections, we analyzed the records of all patients undergoing botox injection therapy for esophageal motility disorders at four university hospitals in Europe and North America between 2008 and 2014. Complications were assigned grades according to the Clavien-Dindo classification. In 386 patients, 661 botox treatments were performed. Main indications were achalasia (51%) and distal esophageal spasm (DES) (30%). In total, 52 (7.9%) mild complications (Clavien-Dindo grade I) were reported by 48 patients, the majority consisting of chest pain or heartburn (29 procedures) or epigastric pain (5 procedures). No ulceration, perforation, pneumothorax, or abscess were reported. One patient died after developing acute mediastinitis (Clavien-Dindo grade V) following injections in the body of the esophagus. In univariate logistic regression, younger age was associated with an increased risk of complications (OR 1.43, 95%CI 1.03-1.96). Treatment for DES, injections into the esophageal body, more injections per procedure, more previous treatments and larger amount of injected botulinum toxin were no risk factors for complications. Esophageal botox injection seems particularly appropriate for high-risk patients due to low complication rate. However, it should not be considered completely safe, as it is associated with rare side effects that cannot be predicted.

Sleep disturbance and enhanced esophageal capsaicin sensitivity in patients with gastroesophageal reflux disease.

BACKGROUND AND AIM: Esophageal infusion of capsaicin-containing red pepper sauce induced heartburn symptoms in patients with gastroesophageal reflux disease (GERD). We aimed to test the hypothesis whether sleep disturbance modulates esophageal sensitivity to capsaicin infusion in patients with GERD. METHODS: We enrolled 40 patients with their sleep quality measured by the Pittsburg Sleep Quality Index with > 5 indicating sleep disturbance. Esophageal sensation to capsaicin infusion was documented via measures of lag time to initial heartburn perception, heartburn intensity rating, and sensitivity score by esophageal infusion of capsaicin-containing red pepper sauce. Objective sleep measures were assessed by ambulatory actigraphy. RESULTS: We found 22 patients with sleep disturbance. The patients with sleep disturbance had shorter lag time to initial heartburn perception (P = 0.03) and greater sensory intensity rating (P = 0.02). The sensitivity score for capsaicin infusion was greater in patients with sleep disturbance when compared with those without sleep disturbance (P = 0.04). Actigraphy measures revealed that patients with sleep disturbance also had poor sleep efficiency (P = 0.04), longer average awakening time (P = 0.03), and greater total activity account (P = 0.04). The lag time for perceiving capsaicin infusion was positively correlated with total sleep time (r = 0.43, P = 0.03). CONCLUSIONS: We have shown that GERD patients with sleep disturbance have significantly enhanced heartburn perception to capsaicin infusion as compared with those with normal sleep. Our findings suggest that sleep disturbance is associated with esophageal hypersensitivity to capsaicin infusion in patients with GERD.

Effects of esophageal capsaicin instillation on acid induced excitation of secondary peristalsis in humans.

BACKGROUND/AIM: Esophageal instillation of capsaicin or hydrochloric acid enhances secondary peristalsis. Our aim was to investigate whether intra-esophageal capsaicin infusion can influence symptom perception and physiological alteration of secondary peristalsis subsequent to acid infusion. METHODS: Secondary peristalsis was induced by mid-esophagus injections of air in 18 healthy subjects. Two different sessions including esophageal infusion of hydrochloric acid (0.1 N) following pretreatment with saline or capsaicin-containing red pepper sauce were randomly performed at least one week apart. Symptoms of heartburn and secondary peristalsis were determined and compared between each study session. RESULTS: The intensity of heartburn symptom subsequent to acid infusion was significantly reduced after capsaicin infusion as compared with saline infusion (54 ± 3 vs 61 ± 3; P = 0.03). Capsaicin infusion significantly increased the threshold volume of secondary peristalsis to rapid air injections subsequent to esophageal acid infusion (8.0 ± 0.5 mL vs 4.4 ± 0.3 mL; P < 0.0001). The frequency of secondary peristalsis subsequent to acid infusion was significantly decreased after capsaicin infusion as compared to saline infusion (70% [60-82.5%] vs 80% [70-90%]; P = 0.03). Capsaicin infusion significantly decreased the pressure wave amplitude of secondary peristalsis subsequent to acid infusion during rapid air injections (90.6 ± 8.7 mmHg vs 111.1 ± 11.1 mmHg; P = 0.03). CONCLUSIONS: Capsaicin appears to desensitize the esophagus to acid induced excitation of secondary peristalsis in humans, which is probably mediated by rapidly adapting mucosal mechanoreceptors. High capsaicin-containing diet might attenuate normal physiological response to abrupt acid reflux by inhibiting secondary peristalsis.

[GASTROINTESTINAL COMPLICATIONS OF ANTICOAGULANT THERAPY IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION].

Non-valvular atrial fibrillation is the most common cardiac source of emboli and cardioembolic stroke. Anticoagulants are recommended for preventing stroke in patients with non-valvular atrial fibrillation. Warfarin reduces the risk of stroke in patients with AF by approximately two-thirds. Several novel anticoagulants that can overcome the limitations of warfarin have been introduced in the market or are under development. The NOACs are at least as effective as warfarin for stroke prevention in AF. Bleeding complications, including gastrointestinal bleeding, are common complication of anticoagulant treatment. The NOACs therapy are associated with an increased risk of major gastrointestinal bleeding compared with warfarin, and dabigatran is associated with an increased risk of non-bleeding upper GI symptoms such as dyspepsia and heartburn. This review provides information on the safety and risks of using NOACs, methods of treatment of gastrointestinal complications events in patients with non-valvular atrial fibrillation.

Increased acid responsiveness in vagal sensory neurons in a guinea pig model of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is characterized with eosinophils and mast cells predominated allergic inflammation in the esophagus and present with esophageal dysfunctions such as dysphagia, food impaction, and heartburn. However, the underlying mechanism of esophageal dysfunctions is unclear. This study aims to determine whether neurons in the vagal sensory ganglia are modulated in a guinea pig model of EoE. Animals were actively sensitized by ovalbumin (OVA) and then challenged with aerosol OVA inhalation for 2 wk. This results in a mild esophagitis with increases in mast cells and eosinophils in the esophageal wall. Vagal nodose and jugular neurons were disassociated, and their responses to acid, capsaicin, and transient receptor potential vanilloid type 1 (TRPV1) antagonist AMG-9810 were studied by calcium imaging and whole cell patch-clamp recording. Compared with naïve animals, antigen challenge significantly increased acid responsiveness in both nodose and jugular neurons. Their responses to capsaicin were also increased after antigen challenge. AMG-9810, at a concentration that blocked capsaicin-evoked calcium influx, abolished the increase in acid-induced activation in both nodose and jugular neurons. Vagotomy strongly attenuated those increased responses of nodose and jugular neurons to both acid and capsaicin induced by antigen challenge. These data for the first time demonstrated that prolonged antigen challenge significantly increases acid responsiveness in vagal nodose and jugular ganglia neurons. This sensitization effect is mediated largely through TRPV1 and initiated at sensory nerve endings in the peripheral tissues. Allergen-induced enhancement of responsiveness to noxious stimulation by acid in sensory nerve may contribute to the development of esophageal dysfunctions such as heartburn in EoE.

Changes in the small bowel of symptomatic kidney transplant recipients converted from mycophenolate mofetil to enteric-coated mycophenolate sodium.

BACKGROUND/AIMS: Gastrointestinal (GI) symptoms in renal transplant recipients may be caused due to mycophenolic acid (MPA) toxicity. Using small bowel capsule endoscopy (SBCE) we examined the impact of conversion from Mycophenolate Mofetil (MMF) to enteric-coated formulation of Mycophenolate Sodium (EC-MPS) given to treat GI mucosal lesions. METHODS: Adult kidney-only recipients at least 30 days after transplant, presenting with GI symptoms while receiving MMF completed a Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, underwent SBCE, and had MMF substituted by EC-MPS. After 30 days, GSRS and SBCE were repeated and findings were compared to baseline values. Patients who were still on EC-MPS 6-24 months post-conversion were contacted for completing a follow-up GSRS questionnaire and SBCE. RESULTS: Eighteen out of 23 subjects completed the first part of the study. Subjects' median ages and post-transplant time were 47.5 years old and 4.5 months, respectively. Tacrolimus, MMF and prednisone was the main regimen (94%), with a median MMF dose of 750 mg BID. The average baseline GSRS was 2.99 ± 0.81; it significantly decreased to 2.19 ± 0.8 at 30 days post-conversion. At baseline, 50 had gastric and 89% had small bowel lesions. At 30 days, 29 and 62% of the SBCE were still showing gastric and small bowel lesions, respectively. Of 5 patients in the study extension, 4 had abnormal SBCE findings but have been reporting improvement in their symptoms. CONCLUSION: Stomach and small bowel mucosal lesions are common in kidney recipients with GI symptoms when treated with MMF. Conversion to EC-MPS for 30 days significantly alleviated the GI symptoms; however, no evident correlation with SBCE findings was found.

A rapid, simple questionnaire to assess gastrointestinal symptoms after oral ferrous sulphate supplementation.

BACKGROUND: Oral iron supplementation is often associated with rapid onset of gastrointestinal side-effects. The aim of this study was to develop and trial a short, simple questionnaire to capture these early side-effects and to determine which symptoms are more discriminating. METHODS: The study was a double-blind placebo-controlled randomized parallel trial with one week treatment followed by one week wash-out. Subjects were randomized into two treatment groups (n = 10/group) to receive either ferrous sulphate (200 mg capsules containing 65 mg of iron) or placebo, both to be taken at mealtimes twice daily during the treatment period. Subjects completed the questionnaires daily for 14 days. The questionnaire included gastrointestinal symptoms commonly reported to be associated with the oral intake of ferrous iron salts (i.e. nausea, vomiting, heartburn, abdominal pain, diarrhoea, and constipation). RESULTS: Seventy five per cent of participants reporting the presence of one or more symptoms in the first week of the study were in the ferrous sulphate group. In the second week of the study (i.e. wash-out), 67% of the participants reporting one or more symptom(s) were in the ferrous sulphate group. In the first week of the study (treatment) the number of symptoms reported by participants in the ferrous sulphate group (mean ± SEM = 6.7 ± 1.7) was significantly higher than that for participants in the placebo group (1.2 ± 0.5) (p = 0.01). In the second week of the study (wash-out) the number of symptoms reported by participants in the ferrous sulphate group (4.6 ± 2.0) appeared higher than for participants in the placebo group (1.0 ± 0.7) although this did not reach significance (p = 0.12). Events for which the gastrointestinal symptom questionnaire was most discriminatory between ferrous sulphate and placebo groups were: heartburn, abdominal pain and the presence of black stools (all p ≤ 0.03). CONCLUSIONS: A tool for the detection of commonly-occurring side effects should not require large study numbers to be effective. With just 10 subjects per group (iron or placebo), this simple questionnaire measures gastrointestinal side-effects associated with oral iron (ferrous sulphate) supplementation, and would be appropriate for use in intervention studies or clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02146053 (21/05/2014).

Proton pump inhibitors and gastrointestinal symptoms among patients with COVID-19 infection.

INTRODUCTION: The administration of proton pump inhibitors (PPIs) is anticipated to elevate an individual's susceptibility to enteric infections as a result of altering the gut flora. The influence of PPIs on the clinical manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain. This study aims to investigate the impact of PPI usage on the clinical manifestation of COVID-19, namely its gastrointestinal symptoms. METHODS: This is a cross-sectional cohort study involving COVID-19 patients. Patients were interviewed using a predesigned questionnaire that asked about their demographics, clinical manifestations of COVID-19 infection, and the extent and type of PPIs in use. PPI usage was confirmed by reviewing patients' electronic medical records. The primary outcome was to establish any association between the use of PPI and the symptoms and clinical presentation of COVID-19. RESULTS: Out of a total of 254 participants, 69 (27.2%) were considered PPI users. Patients who were on PPI medications reported a significantly lower rate of myalgia (27.5% vs 51.9%; p = 0.0006) and heartburn (5.7% vs 15.6%; p = 0.03) but had a significantly higher rate of abdominal pain (27.5% vs 13.5%; p = 0.001) and diarrhoea (28.9% vs 14.5%, p = 0.02) when compared to those who were not using PPIs. Patients on PPIs were also shown to have significantly higher odds of developing diarrhoea (OR 2.0, 95% CI: 1.08 to 3.93, p = 0.02) and abdominal pain (OR 2.0, 95% CI: 1.22 to 3.93, p = 0.03), but a lower risk of developing myalgia (OR 0.5, 95% CI: 0.3 to 0.9, p = 0.02) when compared to non-PPI users. CONCLUSION: This study shows that the use of PPIs could impact COVID-19 clinical presentation toward more gastrointestinal manifestations. Further studies investigating the link between other acid suppression medications and COVID-19 manifestations and severity should be carried out.

Prostaglandin E(2) mediates acid-induced heartburn in healthy volunteers.

Prostaglandin E(2) (PGE(2)) plays a major role in pain processing and hypersensitivity. This study investigated whether PGE(2) levels are increased in the esophageal mucosa after acid infusion and whether increases in PGE(2) are associated with heartburn. Furthermore, expression of the PGE(2) receptor EP1 was investigated in human esophageal mucosa. Fourteen healthy male volunteers were randomized to 30-min lower esophageal acid (1% HCl) or saline perfusion. Before and after acid perfusion, endoscopic biopsies were taken from the distal esophagus. PGE(2) concentration (pg/mg protein) and EP1 mRNA and protein in biopsy samples were measured by ELISA, RT-PCR, and Western blotting. Symptom status of heartburn was evaluated with a validated categorical rating scale with a higher values corresponding to increasing intensity. PGE(2) levels in the esophageal mucosa significantly increased after acid infusion (before vs. after acid infusion: 23.2 ± 8.6 vs. 68.6 ± 18.3, P < 0.05), but not after saline infusion (before vs. after saline infusion: 9.3 ± 2.5 vs. 9.0 ± 3.2, NS). Time to first sensation (min) after acid infusion was less than after saline (saline vs. acid infusion: 22.1 ± 4.1 vs. 5.4 ± 1.5, P < 0.05). Intensity of heartburn in the acid-infusion group was also significantly greater compared with saline (saline vs. acid infusion: 54.3 ± 13.1 vs. 178.5 ± 22.8, P < 0.01). Changes in PGE(2) levels in the esophagus correlated with symptom intensity score (r = 0.80, P = 0.029). EP1 mRNA and protein expression were observed in the normal human esophageal mucosa. Esophageal PGE(2) expression is associated with mucosal acid exposure and heartburn.

Comparable effects of capsaicin-containing red pepper sauce and hydrochloric acid on secondary peristalsis in humans.

BACKGROUND AND AIM: We aimed to evaluate whether acute esophageal instillation of capsaicin and hydrochloric acid had different effects on distension-induced secondary peristalsis. METHODS: Secondary peristalsis was induced by slow and rapid air injections into the mid-esophagus after the evaluation of baseline motility in 16 healthy subjects. The effects on secondary peristalsis were determined by esophageal instillation with capsaicin-containing red pepper sauce (pure capsaicin, 0.84 mg) and hydrochloric acid (0.1 N). RESULTS: The administration of capsaicin induced a significant increase in the visual analogue scale score for heartburn as compared with hydrochloric acid (P = 0.002). The threshold volume for generating secondary peristalsis during slow and rapid air distensions did not differ between capsaicin and hydrochloric acid infusions. Hydrochloric acid significantly increased the frequency of secondary peristalsis in response to rapid air distension compared with capsaicin infusion (P = 0.03). Pressure wave amplitude during slow air distension was greater with the infusion of hydrochloric acid than capsaicin infusion (P = 0.001). The pressure wave duration during rapid air distension was longer after capsaicin infusion than hydrochloric acid infusion (P = 0.01). The pressure wave amplitude during rapid air distension was similar between capsaicin and hydrochloric acid infusions. CONCLUSIONS: Despite subtle differences in physiological characteristics of secondary peristalsis, acute esophageal instillation of capsaicin and hydrochloric acid produced comparable effects on distension-induced secondary peristalsis. Our data suggest the coexistence of both acid- and capsaicin-sensitive afferents in human esophagus which produce similar physiological alterations in secondary peristalsis.

Influence of intraluminal acidification on esophageal secondary peristalsis in humans.

BACKGROUND: Secondary peristalsis contributes to clearance of retained refluxate or material from the esophagus. AIM: The goal of our study was to investigate the effects of hydrochloric acid (HCl) on physiological characteristics of esophageal secondary peristalsis in healthy adults. METHODS: After recording esophageal motility baseline for primary peristalsis, secondary peristalsis was stimulated with slow and rapid air injections in the mid-esophageal in 16 healthy subjects. Normal saline and HCl (0.1 N) were separately infused into the esophagus to test whether they had effects on secondary peristalsis. RESULTS: After infusion of HCl, the threshold volume to generate secondary peristalsis was significantly decreased during rapid and slow air infusions (both P < 0.05). The frequency of secondary peristalsis was increased after HCl infusion (90 % [72.5-100 %] versus 85 % [72.5-90 %], P = 0.002). Infusion of HCl significantly increased pressure wave amplitude during rapid and slow air infusions (both P < 0.05). Infusion of saline did not affect any parameters of secondary peristalsis. The occurrence of heartburn was generated in 7 of 16 subjects after infusion of HCl with an increase in visual analogue scale score (12.5). CONCLUSIONS: Our data show that acute esophageal acid infusion enhances sensitivity of distension-induced secondary peristalsis and enhances secondary peristaltic activity. The study supports the evidence of the presence of acid-sensitive afferents in the modulation of distension-induced secondary peristalsis in humans.

Oesophageal sensation in response to high PCO(2) and acidic solutions in nonerosive reflux disease.

BACKGROUND: Heartburn is commonly associated with the presence of acid in the oesophageal lumen. However, in patients with nonerosive reflux disease (NERD), the mechanism by which acid traverses the mucosa is not clear. We hypothesized that the luminal acid signal traverses the oesophageal epithelium in the form of the highly permeant gas CO(2) , which then is reconverted to H(+) in the submucosa. MATERIALS AND METHODS: Ten patients with heartburn, normal upper endoscopy and increased oesophageal acid exposure (NERD patients) and 10 healthy subjects were enrolled. Perceptual responses to intraoesophageal acid (0·1 N HCl solution) and a high PCO(2) solution were determined using a randomized cross over design. Stimulus-response functions to perfusions were quantified by three parameters: lag time to symptom perception, intensity rating and perfusion sensitivity score. RESULTS: In NERD patients, the difference in lag time to typical symptom perception, intensity rating and perfusion sensitivity score between high PCO(2) and acid perfusions was statistically significant (P = 0·02, 0·01 and 0·02, respectively). However, the difference in the same perfusion parameters between acid and high PCO(2) perfusions was nonsignificant in healthy controls. When NERD and controls were compared, the difference between the different perfusion variables was nonsignificant (adjusted to age). CONCLUSIONS: In NERD subjects, acid perfusion reliably evoked heartburn symptoms of greater intensity than in healthy controls. Nevertheless, a high PCO(2) perfusion failed to produce symptoms in either group.

Patient journey in erosive oesophagitis: real-world perspectives from US physicians and patients.

OBJECTIVE: Management of erosive oesophagitis (EE) remains suboptimal, with many patients experiencing incomplete healing, ongoing symptoms, and relapse despite proton pump inhibitor (PPI) treatment. The Study of Acid-Related Disorders investigated patient burden of individuals with EE in a real-world setting. DESIGN: US gastroenterologists (GIs) or family physicians (FPs)/general practitioners (GPs) treating patients with EE completed a physician survey and enrolled up to four patients with EE for a patient survey, with prespecified data extracted from medical records. RESULTS: 102 GIs and 149 FPs/GPs completed the survey; data were available for 73 patients (mean age at diagnosis, 45.4 years). Omeprazole was healthcare professional (HCP)-preferred first-line treatment (60.8% GIs; 56.4% FPs/GPs), and pantoprazole preferred second line (29.4% and 32.9%, respectively). Price and insurance coverage (both 55.5% HCPs) and familiarity (47.9%) key drivers for omeprazole; insurance coverage (52.0%), price (50.0%), familiarity (48.0%), initial symptom relief (46.0%), and safety (44.0%) key drivers for pantoprazole. Only 49.3% patients took medication as instructed all the time; 56.8% independently increased medication frequency some of the time. Despite treatment, 57.5% patients experienced heartburn and 30.1% regurgitation; heartburn was the most bothersome symptom. 58.9% patients believed that their symptoms could be better controlled; only 28.3% HCPs were very satisfied with current treatment options. 83.6% patients wanted long-lasting treatment options. Fast symptom relief for patients was a top priority for 66.1% HCPs, while 56.6% would welcome alternatives to PPIs. CONCLUSION: This real-world multicentre study highlights the need for new, rapidly acting treatments in EE that reduce symptom burden, offer durable healing and provide symptom control.

Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non-exposed human oesophagus.

BACKGROUND: Oesophageal mucosa dilated intercellular spaces (DIS) may be important for symptom perception in non-erosive reflux disease (NERD). Patients with NERD might have DIS even in the proximal oesophagus. We aimed to assess the effect of oesophageal perfusions with acid and weakly acidic solutions on 'exposed' and 'non-exposed' oesophageal mucosa and its relationship to symptoms in healthy subjects. METHODS: 14 healthy volunteers underwent upper gastrointestinal endoscopy with biopsies at 3 and 13 cm proximal to the oesophagogastric junction (OGJ). In following sessions, subjects received 30 min perfusions with neutral, weakly acidic, acidic and acidic-bile acid solutions at 5 cm above the EGJ (separated 4 weeks). Biopsies were taken 20 min after perfusions. Electron microscopy was used to measure DIS. Subjects scored heartburn during perfusions using a visual analogue scale. RESULTS: (1) Oesophageal perfusion with acid solutions, with or without bile acids, provoked DIS in the 'exposed' oesophageal mucosa; (2) oesophageal perfusion with weakly acidic solutions provoked identical changes to those observed after perfusion with acid solutions; (3) distal oesophageal perfusions not only provoked changes in the 'exposed' but also in the more proximal 'non-exposed' mucosa; and (4) in spite of the presence of perfusion-induced DIS, most healthy subjects did not perceive heartburn during the experiments. CONCLUSIONS: The human oesophageal mucosa is very sensitive to continuous exposure with acidic and weakly acidic solutions. In spite of the presence of intraluminal acid and DIS, healthy subjects did not experience heartburn, suggesting that NERD patients should have other critical factors underlying their symptoms.