Esophageal Mucosal Injury Research Articles

Therapeutic Strategy for the Overlap Between GERD and Function Dyspepsia: Study of Additive Effect Acotiamide on Rabeprazole

Background: Proton pump inhibitors (PPIs), the first-choice agents for the treatment of gastroesophageal reflux disease (GERD), cure most GERD patients, but there are still patients in whom symptom improvement is poor despite remission of esophageal mucosal injury. Since the symptoms of such PPI-refractory GERD patients overlap with functional dyspepsia (FD). In Japan, acotiamide was approved as the world's first drug for FD. Acotiamide is known to improve gastrointestinal tract motility by inhibiting acetylcholine esterase, but the therapeutic effect on the overlap between GERD and FD is unknown. A phase II study on acotiamide has been completed in the U.S. Objective: To study the improvement of symptoms when acotiamide was administered in addition to rabeprazole to treat the overlap between GERD and FD. Patients and methods: This study was conducted as a prospective, single-institution, open-label study. Twenty six patients were enrolled, who had a Grade A or higher mucosal injury according to the Los Angeles (LA) classification as judged by esophagogastroduodenoscopy (EGD) and remnant epigastric symptom, but in whom ECG indicated healing of mucosa after oral administration of 10 mg/day rabeprazole for 8 weeks or more. After examination of background factors, 300 mg/day acotiamide was added to 10 mg/day rabeprazole. The symptoms were examined again after 4 weeks to investigate the therapeutic effect. We used an Izumo scale questionnaire, which scores heartburn, epigastralgia, and epigastric fullness from 0 to 15 points each. Results: Twenty six subjects consisting of 11 males and 15 females were evaluated. Before and after adding acotiamide, heartburn scores were 4.2 and 3.0, respectively, demonstrating a significant decrease (improvement rate, 29%; p=0.044); epigastralgia scores were 3.8 and 3.1, respectively, indicating no significant difference (improvement rate, 18%; p=0.089); epigastric fullness scores were 7.0 and 3.8, respectively, demonstrating a significant decrease (improvement rate, 46%;p=0.0001); total scores of these three epigastric symptoms were 14.9 and 10.0, respectively, demonstrating a significant decrease (p=0.0002). Score decreased by 50% or more in 31% of subjects. Conclusions: Even if PPI administration improves mucosal injury, it is often difficult in clinical practice to treat the overlap between GERD and FD, with which epigastric symptom improvement with PPI treatment is poor. This study suggests that adding acotiamide to PPI is potentially effective in improving the symptoms in treating such patients.

Dabigatran-induced asymptomatic esophageal mucosal injury

Dabigatran-induced asymptomatic esophageal mucosal injury

Esophageal abnormalities in morbidly obese adult patients.

An increase in body mass index has been found to be associated with an increase in the prevalence of gastroesophageal reflux disease (GERD) symptoms, esophageal mucosal injury, and GERD complications. Few systematic studies with objective tests have evaluated esophageal disorders in the morbidly obese population. To define more precisely in morbidly obese people the incidence of esophageal symptoms and characterize the esophageal disorders using objective data. University Hospital, Spain. Two hundred twenty-four presurgical morbidly obese patients were submitted to a protocol including a clinical history and objective tests (endoscopy, stationary esophageal manometry, 24-hour esophageal pH monitoring and isotopic emptying of the esophagus). In a morbidly obese population, heartburn (50.9%) and regurgitation (28.6%) were the most prevalent symptoms of GERD. Endoscopy registered hiatus hernia (12.5%) and reflux esophagitis (17.3%). Manometry was often abnormal (33.4%), with a hypotensive lower esophageal sphincter as the most common finding. Esophageal pH-metry was abnormal in 54.2% of the cases. Finally, 9.1% of the patients presented with abnormal isotopic esophageal emptying. A correlation between the degree of obesity and the severity of symptoms/objective tests for esophageal abnormalities could not be found. In morbidly obese patients, GERD is common, symptoms are unspecific, and there is a high prevalence of pH-metry and manometric abnormalities, unrelated to the degree of obesity.

Protective effects of quercetin against chronic mixed reflux esophagitis in rats by inhibiting the nuclear factor-κB p65 and interleukin-8 signaling pathways.

To observe the effects of quercetin on chronic mixed reflux esophagitis (RE) in rats by inhibiting the nuclear factor-κB p65 (NF-κBp65) and interleukin-8 (IL-8) signaling pathways. Forty-eight healthy male Sprague-Dawley rats were randomly divided into six groups, with 8 rats in each group: the normal intact group, the sham operation group, the RE control group, the RE group treated with omeprazole or 100 mg/kg and 200 mg/kg quercetin. The animals were sacrificed after 6 weeks of different interventions. The pathological characteristics of esophageal mucosa were observed according to the diagnostic criteria and the expressions of NF-κBp65 and IL-8 were assessed by immunohistochemistry and real-time polymerase chain reaction. Compared with the RE control group, esophageal mucosal injury was improved and the expressions of NF-κBp65 and IL-8 were significantly decreased in the RE group treated with omeprazole or quercetin (P < 0.05). Compared with the omeprazole group, the gross and microscopic scores of esophageal mucosal injury and the expressions of NF-κBp65 and IL-8 in the 100 mg/kg and 200 mg/kg quercetin groups were not increased (P > 0.05). There was no statistically significant difference between the RE groups treated with 100 mg/kg quercetin and 200 mg/kg quercetin. Quercetin can prevent esophageal mucosal injury in RE rats by suppressing the NF-κBp65 and IL- 8 signaling pathways.

"Normal Values of 24H Multichannel Intraluminal Impedance pH-Metry in a Greek Obese Population Based on Montreal Definition of Gerd".

Although several studies reporting normal values of 24h multichannel intraluminal impedance pH (MIIpH) have been published, none of them has ever studied obese individuals. The purpose of this study is to determine overall frequency and duration of reflux episodes (acid and non-acid, supine-upright, post and preprandial) in obese asymptomatic volunteers. Obese volunteers were enlisted during their preoperative evaluation for bariatric surgery. Volunteers had no gastroesophageal reflux disease (GERD) symptoms and no evidence of esophageal mucosal injury on endoscopy. Participants underwent a 24h MIIpH. In this prospective observational study, data of 22 obese individuals were analyzed. Mean age was 41.9 years and mean BMI was 47.1 kg/m(2). Mean total reflux episodes was 55.6 and 95th percentile was 99.7. Mean percentage of total time with pH <4 was 2.59 % and 95th percentile was 8.57 %. Mean percentage of bolus exposure was 1.84 % with 95th percentile being 4.47 %. Postprandial acid reflux episodes were statistical significant more frequent in comparison to preprandial acid reflux episodes (19.41 vs. 15, p = 0.008). Mean acid clearance duration was 3.6 times higher than median bolus clearance duration (56.05 and 15.55 s, respectively, p = 0.868). Our study is the first to provide normal values of 24h MIIpH of asymptomatic obese. Normal values of 24h MIIpH of obese asymptomatic individuals differ from the reported normal values of non-obese healthy individuals; having more reflux episodes and equal or slightly higher median bolus exposure and acid clearance. Our results imply that new cut-off values should be employed in order to define GERD in obese individuals.

Association between visceral fat and inflammatory cytokines in reflux esophagitis.

The results of several previous studies have suggested that abdominal obesity is an important risk factor for reflux esophagitis.1,2 Among factors related to obesity, visceral fat is more associated with erosive esophagitis than body mass index (BMI).3 Physiologic abnormalities related to prolonged esophageal acid exposure have been found to occur more frequently in obese individuals than in those with normal weight. Obese subjects revealed abnormal esophageal manometric findings such as nonspecific motility disorder, nutcracker esophagus, and hypotensive lower esophageal sphincter as the most common manometric results.4 Transient relaxations of the lower esophageal sphincter (TRLES) is also reported to be more common in patients with obesity. The main stimulus for TRLES is gastric distension especially in the gastric fundus.5 Pandofino et al6 reported esophageal manometric findings suggesting that the pressure morphology within and across the esophagogastric junction were altered in obesity, which could augment the flow of gastric juices into the esophageal lumen. This anatomical disruption of the esophagogastric junction results in further hiatal hernia formation. Esophageal mucosal injury is associated with increased exposure to gastric acid. However, maintenance of chronic esophageal mucosal inflammation and esophageal metaplasia such as Barrett’s esophagus (BE) or esophageal carcinoma in obese subjects have been proposed to increase inflammatory cytokines from visceral adipose tissue.7 The relationship between obesity and esophageal neoplasia may be due to alterations in the secretion of adipokines such as adiponection and leptin. Adiponection has an anti-inflammatory effect and stimulates apoptosis, which shows inverse relationship between obesity and adiponection.8 Leptin, a satiety hormone, is secreted by adipocytes and gastric chief cells. Esophageal epithelial cells express leptin receptors. In an esophageal adenocarcinoma cell line, leptin has been shown to stimulate cell proliferation and inhibit apoptosis via cyclooxygenase-2 activation of the epidermal growth factor receptor.9 Several studies have suggested a positive association between plasma leptin and BE.10,11 Kendall et al12 reported that a high serum leptin level is associated with an increased risk of BE among men, but not women. No previous reports have documented the relationship between circulating cytokines and reflux esophagitis (RE). Recently, Nam13 conducted an interesting case-control study that suggested circulating cytokines were correlated with the risk of erosive esophagitis. They used abdominal visceral fat instead of BMI and plasma leptin level had a positive correlation with RE. The visceral fat/total fat ratio was used as an obesity index because there is no standard cut off value for defining obesity. The results indicated that both visceral fat and the visceral fat/total fat ratio were positively correlated with IL-6, IL-8, and IL-1β, but were negatively associated with adiponectin. Leptin showed no association with visceral fat, but had a strong association with the visceral fat/total fat ratio. Only visceral fat/100 and leptin were positively correlated with RE after adjusted analysis for both inflammatory cytokines and obesity indexes. Despite the positive correlation of visceral fat and leptin with risk of RE, they did not classified reflux symptom strength or severity of esophagitis. Moreover, cytokine has its effect through ligand mediate reaction. Elevated plasma levels of cytokines do not always reflect cytokine bioactivity in inflamed regions. Checking the receptor expression and cytokine levels in target tissue provides more information about cytokine-ligand mediated responses.14,15 In conclusion, obesity is an important risk factor for developing gastroesophageal reflux disease. Abdominal visceral fat is a more useful obesity index for RE than BMI. To clarify the role of circulating cytokines in obese subjects with RE, further studies with large populations are needed, which will also help elucidate the pathophysiology between obesity and RE.

Upper gastrointestinal mucosal injury and symptoms in elderly low-dose aspirin users.

Background. We investigated the prevalence, symptoms, and QOL impact of esophageal (EI), gastric (GI), and duodenal mucosal injury (DI) individually between low-dose aspirin (LDA) users and nonusers to reveal the clinical features of LDA-related mucosal injury. Methods. Data were extracted from the records of subjects who underwent upper gastrointestinal endoscopy at our department between April 2008 and December 2013. Responses from 3162 elderly patients on Frequency Scale for Symptoms of GERD (FSSG) and SF-8 QOL questionnaires (SF-8) were analyzed. FSSG items were classified into total score (TS), reflux score (RS), and dyspepsia score (DS). The SF-8 questionnaire consisted of the physical component summary (PCS) and mental component summary (MCS). Results. Prevalence among LDA users and nonusers, respectively, was 9.6% and 10.0% (P = 0.83) for EI, 35.9% and 27.5% (P = 0.0027) for GI, 3.3% and 3.4% (P = 0.84) for DI, and 8.2% and 5.2% (P = 0.036) for mucosal injury in 2 or more organs. LDA users diagnosed with EI had significantly lower PCS, LDA users diagnosed with GI had significantly lower DS, and LDA users diagnosed with DI had significantly lower RS and significantly lower MCS. Conclusion. These results provide important clinical information indicating that symptom-based management is not appropriate in LDA users regarding upper gastrointestinal mucosal injury.

Caustic injury of upper gastrointestinal tract: 20 year experience at a tertiary referral center

Caustic ingestion can cause severe injury to upper gastrointestinal tract. There were few studies about clinical characteristics and treatments of caustic injury in Korea. We investigated the changes in clinical features of caustic injury over the past 20 years including pattern of endoscopic mucosal injury and treatment modality. This study was a retrospective review of medical records from patients with caustic injury from September 1993 through December 2012. Patients were classified into two groups based on the year when caustic ingestion occurred: patients who visited the hospital from 1993 to 2002 (early group) and patients who visited the hospital from 2003 to 2012 (late group). A total 140 patients were included (early group [n=50] vs. late group [n=90]). Annual number of caustic ingestions did not show decreasing tendency over the past 20 years. Alkali ingestion increased (20.0% vs. 65.6%, p<0.001) and cases with more than grade 2b of esophageal mucosal injury decreased (41.3% vs. 20.7%, p=0.012) in late group. There were no differences between two groups in sex, age, proportion of accidental ingestion, and systemic/gastrointestinal complications. Use of gastric lavage (p<0.01) and broad spectrum antibiotics (p=0.03) decreased in late group. However, there was no difference in use of steroid between two groups. In this study, overall caustic ingestion did not decrease and ingestion of alkali agents increased over the past 20 years. Tighter legislation on caustic agents is required and we need to be alert to the best management of caustic injury.

Doxycycline Induced Esophageal Ulcer: TwoCases Report

It has been established that drugs can induce esophageal mucosal injury. Doxycycline induced esophageal injury has contributed to most of drug induced esophageal injuries. In this study, two cases are presented. Two females who are 27 and 30 year sold, applied to our hospital witht he complains of an acute onset odynophagia, dysphagia and retrosternal pain after using doxycycline for their genital system infection. Endoscopic examination detected semicircular deep ulceration at the middle esophagus. Their symptoms improved after 3 days of initiation of pantoprazole and liquid sucralfate following discontinuation of doxycycline. Drug induced esophageal injury is a common condition. Use of drug should be investigated in patients presenting with similar symptoms.

A distinct salivary secretory response mediated by the esophago-salivary reflex in patients with Barrett's esophagus: Its potential pathogenetic implications

PurposeA significantly compromised epidermal growth factor (EGF) secretion by basal parotid saliva may contribute to the development of Barrett's esophagus (BE). The rate of secretion of EGF as well as a wide spectrum of protective factors in total basal and stimulated saliva in BE patients remains to be explored. We therefore studied the rate of secretion of salivary buffers, glycoconjugate, protein, EGF, transforming growth factor α (TGFα) and prostaglandin E2 (PGE2), evoked by esophago-salivary reflex, in patients with BE and controls (CTRL). Material/methodsSalivary secretion was collected during basal condition, mastication, and intraesophageal mechanical and chemical stimulations respectively, mimicking the natural gastroesophageal reflux scenario. ResultsSalivary pH in BE was significantly lower than in controls during mechanical (p<0.001) and chemical stimulations (p<0.001). Bicarbonate and protein outputs in BE were significantly lower during mechanical (p<0.05) and chemical stimulations (p<0.01). The non-bicarbonate and glycoconjugate outputs in BE were lower during chemical stimulation (p<0.05) and during mechanical (p<0.05) and chemical stimulations (p<0.05) respectively. The rate of salivary EGF output in BE was significantly lower during mechanical stimulation (p<0.05). We observed a higher TGFα output during mastication (p<0.05) and PGE2 secretion during basal and masticatory condition (p<0.05) in BE. ConclusionsPatients with BE demonstrated significantly compromised salivary pH and rate of secretion of bicarbonate, non-bicarbonate, glycoconjugate, protein and EGF. This impairment could potentially predispose to the development of accelerated esophageal mucosal injury. Potential restoration of this impairment by masticatory stimulation of salivary secretion using sugarless chewing gum justifies further clinical exploration.

Comparison of Light and Electron Microscopy in Measurement of Esophageal Intercellular Space in Children

A good objective marker of esophageal mucosal damage from gastroesophageal reflux disease (GERD) is lacking in children. Increased esophageal epithelial intercellular (EEIC) space measured using electron microscopy (EM) has been proposed as a surrogate of esophageal mucosal damage in adults with GERD. The aim of the present study was to compare EEIC space measured using EM and light microscopy (LM) in children with nonerosive reflux disease (NERD) with asymptomatic controls. Distal esophageal mucosal biopsy was used to measure EEIC space using EM in 35 NERD subjects and 8 controls. In a subset of these patients we used phase contrast LM to measure EEIC space area (26 NERD subjects and 8 controls). The median (range) EEIC space measured using EM in the NERD group was 1.15 (0.74-1.64) μm compared with 0.93 (0.67-1.11) μm in the control group (P = 0.002). The median (range) EEIC space measured using LM was 14.4% (9.6%-26.3%) in the NERD group and 9.6% (8.5%-17.2%) in controls (P = 0.003). Using a cutoff value of 1.02 μm for normal EEIC space measured by EM, we obtained 73% sensitivity and 75% specificity to distinguish the NERD group from the control group, and using a cutoff value of 11.1% for EEIC space measured by LM, we obtained 96% sensitivity and 75% specificity. EEIC space is increased in children with NERD compared with that in controls, suggesting that changes in EEIC space can be a useful marker of esophageal mucosal injury in children with NERD. Our results suggest that the accuracy of EM and LM to evaluate EEIC space changes in NERD is comparable, and LM may be a more cost-effective option.

Association of reflux symptom index scores with gastroesophageal flap valve status.

Gastroesophageal reflux disease is a chronic symptom of mucosal damage caused by gastric acid reflux. Impaired gastroesophageal flap valve (GEFV) is one of the common etiologic factors of gastroesophageal reflux. The aim of this study was to investigate the association between GEFV, RSI, and GER in patients who underwent gastroesophageal endoscopy. Two hundred and fifty seven consecutive patients with reflux symptoms (151 men and 106 women, mean age was 50.22 years) who underwent routine upper gastrointestinal endoscopy were enrolled to our study. GEFV was graded as I through IV according to the Hill's classification. Symptoms of laryngopharyngeal and upper gastrointestinal disease and endoscopic severity of esophageal injury were correlated with GEFV status. The GEFV was classified into two groups: normal GEFV group (grade I) and the abnormal GEFV group (grades II-III and IV). The reflux symptom index (RSI) was used as a diagnostic tool for LPR. Age, male gender, and body mass index were significantly related to an abnormal GEFV. The rate of abnormal grades of GEFV (Grade II+III+IV) was 31%. Age of normal and abnormal grades of GEFV (49.0/50.8 vs 52.9) and values of BMI (26.2/26.7 vs 26.5) were similar. RSI scores were correlated with gastroesophageal flap valve grades but RSI scores were not correlated with Los Angeles gastroesophageal reflux (GER) Classification. Moreover, gastroesophageal reflux grade of Los Angeles Classification was positively correlated with gastroesophageal flap valve grades. Endoscopic grading of GEFV is a simple and useful technique which may provide an accurate diagnosis of laryngopharyngeal and gastroesophageal reflux. Also, reflux symptom index (RSI) is a simple, economic and noninvasive diagnostic tool for gastroesophageal reflux. However, in this research, we did not find any correlation between reflux symptom index and degree of esophageal mucosal injury which was classified according to LA classification.

Efficacy and durability of robotic Heller myotomy for achalasia: patient symptoms and satisfaction at long-term follow-up.

Laparoscopic Heller myotomy (LHM) has become the standard treatment for achalasia in the USA. Robot-assisted Heller myotomy (RHM) has emerged as an alternative approach due to improved visualization and fine motor control, but long-term follow-up studies have not been reported. We sought to report the long-term outcomes of RHM and compare them to those of LHM. A retrospective cohort study was performed for patients who underwent laparoscopic or RHM between 1995 and 2006. Long-term follow-up was performed via mail or telephone questionnaire. The primary outcome measure was durable relief of dysphagia without need for further intervention. Secondary outcomes included gastroesophageal reflux symptoms, disease-specific quality of life, and patient satisfaction with their operation. Seventy-five patients underwent laparoscopic (n = 19) or robotic (n = 56) myotomy during the study period. Long-term follow-up was obtained in 53 (71 %) patients with a median interval of 9 years. RHM was associated with a decreased mucosal injury rate (0 vs. 16 %, p = 0.01) and median hospital stay (1 vs. 2 days, p < 0.01) compared to conventional laparoscopy. All patients reported initial dysphagia relief, and 80 % required no further intervention. This did not differ between groups. Sixty-two percent required medications to control reflux symptoms at long-term follow-up, including 56 % following robotic myotomy and 80 % after laparoscopic myotomy (p = 0.27). Overall, 95 % of patients were satisfied with their operation, and 91 % would choose surgery again given the benefit of hindsight. There is a dearth of long-term follow-up data to support the effectiveness of RHM. This study demonstrates durable dysphagia relief in the vast majority of patients with a high degree of patient satisfaction and a low rate of esophageal mucosal injury. While a significant proportion of patients report reflux symptoms, these symptoms are well controlled with medical acid suppression.

Endoscopic evidence of reflux disease in the larynx

Conclusion: The severity of laryngeal mucosal lesions in patients with gastroesophageal reflux disease (GERD) is significantly greater than in controls. A higher degree of laryngeal mucosal injury is documented in patients in whom GERD is associated with more advanced esophageal lesions. Objectives: (1) To confirm the presence of inflammatory lesions in the laryngopharynx of patients with GERD. (2) To analyze the relationship between the severity of laryngopharyngeal and esophageal lesions on the basis of the reflux finding score (RFS) and the Los Angeles (LA) scale of esophageal mucosal injury. Methods: The study included 92 subjects, among them 46 patients with GERD and 46 individuals without endoscopic evidence of esophageal lesions, qualified for routine endoscopy due to other indications. The endoscopic images of the inferior pharynx, larynx, and esophagus were analyzed during the video-endoscopic examination of the upper gastrointestinal tract. The laryngeal images were assessed according to RFS criteria and the numeric value of RFS was calculated. The degree of esophageal mucosal injury was described according to the LA scale. Results: Both global RFS score and the scores of all RFS parameters except the presence of granulomatous tissue were significantly higher in patients with GERD than in the controls. Patients in whom GERD was associated with more severe esophageal lesions (group B according to the LA scale) had significantly higher global RFS score and scores of all analyzed parameters of laryngeal injury except subglottic edema than individuals in whom the degree of esophageal involvement was classified as group A.

Tu1399 Therapeutic Strategy for the Overlap Between GERD and Functional Dspepsia —Study of Additive Effect of Acotiamide on Rabeprazole—

Proton pump inhibitors (PPIs), the first-choice agents for the treatment of gastroesophageal reflux disease (GERD), cure most GERD patients, but there are still patients in whom symptom improvement is poor despite remission of esophageal mucosal injury. Since the symptoms of such PPI-refractory GERD patients overlap with those in postprandial distress syndrome and epigastric pain syndrome, it is inferred that GERD sometimes overlaps with functional dyspepsia (FD). Acotiamide is known to improve gastrointestinal tract motility by inhibiting acetylcholine esterase, but the therapeutic effect on the overlap between GERD and FD is unknown.

Salivary Bicarbonate as a Major Factor in the Prevention of Upper Esophageal Mucosal Injury in Gastroesophageal Reflux Disease

It has been previously demonstrated that the exposure of the lower esophageal mucosa to acid and pepsin results in significant increase in salivary protective factors secretion, mediated by the esophago-salivary reflex. The impact of the upper esophageal mucosal exposure to acid and pepsin on salivary secretory response remains unknown. To investigate the rate of salivary protective factors secretion during the upper esophageal mucosal exposure to acid and pepsin and to compare with the corresponding results recorded during the lower esophageal mucosal exposure, in the same group of asymptomatic volunteers. The study was conducted in 10 asymptomatic volunteers. Salivary samples were collected during the esophageal mucosal exposure to saline, followed by acid/pepsin and the final saline, using the esophageal perfusion catheter. Salivary bicarbonate and non-bicarbonate buffers were analyzed using TitraLab. Salivary mucin and protein were quantified through PAS and Lowry methodologies, respectively, whereas PE2 using radioimmunoassay. Statistical analysis was performed using Σ-Stat software. The rate of salivary bicarbonate secretion was significantly higher (3.1-fold) during the upper versus the lower esophageal mucosal exposure to acid and pepsin (87.5±14.4 vs. 28.0±7.70μEq/min, p<0.05). The volumes of saliva, pH, salivary protein, mucin and PE2 were similar in both esophageal perfusions. Threefold stronger secretion of salivary bicarbonate could be a major factor protecting the upper esophageal mucosa. This phenomenon may represent an ultimate defense mechanism potentially preventing further complications within the upper esophageal mucosa; however, it needs to be confirmed in patients of gastroesophageal reflux disease.

Dilated intercellular space diameter as marker of reflux‐related mucosal injury in children with chronic cough and gastro‐oesophageal reflux disease

The diagnostic corroboration of the relationship between gastro-oesophageal reflux disease (GERD) and chronic cough remains challenging. To compare oesophageal mucosal intercellular space diameter (ISD) in children with GERD, children with gastro-oesophageal reflux (GER)-related cough (GrC) and a control group, and to explore the relationship between baseline impedance levels and dilated ISD in children with GER-related cough. Forty children with GERD, 15 children with GrC and 12 controls prospectively underwent oesophagogastroduodenoscopy (EGD) with oesophageal biopsies taken 2-3cm above squamocolumnar junction. ISD were quantified using transmission electron microscopy. Impedance-pH monitoring with evaluation of baseline impedance in the most distal impedance channel was performed in both patient groups. A significant difference in mean ISD values was found between GrC patients (0.9±0.2μm) and controls (0.5±0.2μm, P<0.001), whereas there was no difference between GrC and GERD group (1±0.3μm, NS). No difference was found in the mean ISD between GrC children with or without pathological oesophageal acid exposure time (1±0.3 vs. 0.9±0.2μm), and there was no correlation between ISD and any reflux parameter. Finally, there was no correlation between ISD and distal baseline impedance values (r:-0.35; NS). In children with reflux-related cough, dilated intercellular space diameter appears to be an objective and useful marker of oesophageal mucosal injury regardless of acid exposure, and its evaluation should be considered for those patients where the diagnosis is uncertain. In children with reflux-related cough, baseline impedance levels have no role in identifying reflux-induced oesophageal mucosal ultrastructural changes.

Geranylgeranylacetone, a Gastromucoprotective Drug, Protects Against NSAID-induced Esophageal, Gastroduodenal and Small Intestinal Mucosal Injury in Healthy Subjects: A Prospective Randomized Study Involving a Comparison with Famotidine

A treatment strategy to inhibit nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal lesions has not yet been established. To clarify whether monotherapy with a gastromucoprotective drug, geranylgeranylacetone (GGA), inhibits NSAID-induced acute mucosal injury of the upper digestive tract and small intestine. A prospective, randomized, comparative study. All procedures were performed at Osaka Medical College. The subjects, thirty healthy adult volunteers, were randomly divided into two groups. In the NSAID-GGA group, 75 mg/day of diclofenac sodium and 150 mg/day of GGA were orally administered for two weeks. In the NSAID-FAM group, 75 mg/day of diclofenac sodium and 20 mg/day of famotidine (FAM) were orally administered for two weeks. esophagogastroduodenoscopy (EGD) and video capsule endoscopy (VCE) were performed before and two weeks after drug administration. In addition, we measured fecal occult blood reactions and the fecal calprotectin levels. No significant differences were observed between the groups in the mean increase in esophageal/gastroduodenal lesions. The mean increases in the scores in the NSAID-FAM group (NSAID-GGA group) of small bowel lesions were as follows: erythema: 1.93 ± 0.67 (0.30 ± 0.60), erosions: 1.13 ± 0.54 (0.38 ± 0.35), ulcers: 0.73 ± 0.33 (0.07 ± 0.07) and edema: 0.53 ± 0.44 (0.07 ± 0.07). The scores for erythema and ulcers were significantly lower in the NSAID-GGA group than in the NSAID-FAM group (p=0.032 and 0.0165, respectively). We compared the prophylactic effects of a mucoprotective drug, GGA, and an H2RA, famotidine, on mucosal injury involving the esophagus to the small intestine related to the two-week oral administration of diclofenac sodium in healthy volunteers. In the upper digestive tract, the prophylactic effects were similar between the two drugs. However, in the small intestine, GGA more markedly inhibited the development of lesions compared to famotidine.

Impairment of Salivary Mucin Production Resulting in Declined Salivary Viscosity During Naproxen Administration as a Potential Link to Upper Alimentary Tract Mucosal Injury

OBJECTIVES:Nonsteroidal anti-inflammatory drugs (NSAIDs) contribute to the esophageal mucosal injury through its direct topical impact on the luminal aspect of the surface epithelium. Its indirect, systemic impact, however, on salivary component of the esophageal pre-epithelial barrier remains to be explored. Therefore, salivary mucin secretion and viscosity at baseline and during naproxen-placebo, as well as naproxen-rabeprazole, administration were investigated.METHODS:Twenty-one asymptomatic volunteers were included in this double-blind, placebo-controlled, crossover designed study. Salivary samples were obtained in basal and pentagastrin-stimulated conditions (6 mg/kg s.c.) mimicking the food-stimulated conditions. Patients received 7 days of naproxen-placebo or naproxen-rabeprazole with a 2-week washout period in between. Salivary mucin content and viscosity were measured before and after treatment using periodic acid/Schiff's methodology and Cone/Plate Digital Viscometer, respectively.RESULTS:The rate of salivary mucin secretion in basal condition declined by 32% during administration of naproxen-placebo (11.3±1.7 vs. 16.8±3.3 mg/h). Salivary mucin secretion in pentagastrin-stimulated condition declined significantly (by 34%) during the administration of naproxen-placebo (13.6±1.5 vs. 20.7±3.0 mg/h; P<0.05). Viscosity significantly decreased after naproxen-placebo administration in basal (by 60%) and stimulated conditions (by 56%) (P<0.001). Coadministration of rabeprazole at least partly restored the naproxen-induced decline of salivary mucin in basal condition (by 8%), and pentagastrin-stimulated conditions (by 30%).CONCLUSIONS:A significant decline of salivary mucin and viscosity during administration of naproxen may at least partly explain a propensity of patients on chronic therapy with NSAIDs to the development of esophageal mucosal injury and complications. In addition the trend to restorative capacity of rabeprazole on the quantitative impairment of salivary mucin during administration of naproxen may potentially translate into its tangible clinical benefit but it requires further investigation.

Doxycycline-induced Gastric and Esophageal Mucosal Injuries With Vascular Degeneration

Xiao, Shu-Yuan MD*; Zhao, Lei MD, PhD*; Hart, John MD*; Semrad, Carol E. MD† Author Information