Chronic Reflux Research Articles

Assessment of food specific immunoglobulin load in pre-school children

This article was originally published online on 8 April 2015 Chronic diarrhea, vomiting, reflux, bloating, flatulence, and chronic stomach pain accompanied by cranky behavior are common symptoms related to delayed food sensitivity reactions in preschool children ranging from one to five years of age. It is not known whether immune intolerance and/or inflammatory reactions are playing any role in these children due to over-reactivity to food specific immunoglobulin load. At Alletess Medical Laboratory, we analyzed 966 preschool children. Our 96 food ELISA assay was used to assess food specific IgG antibody loads at three different levels low (10 – 25 ug/ml), moderate (25 – 50 ug/ml), and high (>50 ug/ml). The 96 foods were categorized into dairy products, animal proteins, grains, nuts, fish, shell fish, herbs, spices, vegetables, and fruits groups. Our results revealed the following percentages of this subpopulation with high IgG antibody loads: dairy products (18 - 21%), grain/seeds (19 - 32%), eggs (29%), tree nuts (6 - 20%), peanuts (29%), animal proteins (< 2%), vegetables and fruits (< 5%), and yeasts (3 - 13%). Overload of food specific IgG antibodies could be the cause of intolerance and/or symptoms related to inflammatory reactions of the bowels. The burden related to this IgG overload could be lowered by replacing offending foods with well-balanced food alternatives in preschool children in order to improve their overall wellness.

The Status of Histopathology in the Diagnosis of Gastroesophageal Reflux Disease – Time for Reappraisal?

The histological diagnosis of gastroesophageal reflux disease is generally believed to be a tool of limited value. Recent data, however, indicate that histology may be useful for the management of patients with non-erosive reflux disease, who account for up to 60% of all patients with reflux symptoms. Early diagnosis of gastroesophageal reflux disease is crucial because chronic reflux esophagitis is a key risk factor for the development of Barrett´s esophagus, which predisposes to esophageal adenocarcinoma. Histologically, reflux esophagitis is characterized by basal cell hyperplasia, papillary elongation, dilation of intercellular spaces, and inflammatory infiltration. These reflux-induced changes of the squamous epithelium are mainly related to the diagnosis of acute and/or active reflux. The chronic consequences of gastroesophageal reflux disease are mainly characterized by metaplatic mucosal replacement. The origin and significance of cardiac mucosa at the gastroesophageal junction are still controversial However, evidence is accumulating that injury and repair related to gastroesophageal reflux disease contribute to its development and/or expansion. Multilayered epithelium, defined as hybrid epithelium with characteristics of both squamous and columnar epithelium has been identified as a new sensitive marker of gastroesophageal reflux disease. This epithelium may be the precursor of metaplastic cardiac mucosa, and ultimately Barrett’s esophagus.

Role of proton pump inhibitor on esophageal carcinogenesis and pancreatic acinar cell metaplasia development: an experimental in vivo study.

Chronic gastro-duodenal reflux in the esophagus is a major risk for intestinal metaplasia and Barrett’s adenocarcinoma. A role for chronic use of proton pump inhibitor (PPI) in the increased incidence of esophageal adenocarcinoma in Western countries has been previously suggested. The aim of this work was to study the effect of chronic administration of omeprazole (a proton pump inhibitor) per os in a model of reflux induced esophageal carcinogenesis. One week after esophago-gastro-jejunostomy, 115 Sprague-Dawley rats were randomized to receive 10 mg/Kg per day of omeprazole or placebo, 5 days per week. The esophago-gastric specimens were collected 28±2 weeks after randomization and analyzed in a blinded fashion. Mortality and esophageal metaplasia rates did not differ between the two groups (p = 0.99 for mortality, p = 0.36 for intestinal metaplasia and p = 0.66 for multi-layered epithelium). Gastric pancreatic acinar cell metaplasia (PACM) was more frequently observed in PPI-treated rats (p = 0.003). Severe ulcer lesions significantly prevailed in the placebo group (p = 0.03). Locally invasive esophageal epithelial neoplasia were observed in 23/39 PPI-treated versus 14/42 placebo-animals (p = 0.03). In conclusion, chronic omeprazole treatment improved the healing of esophageal ulcerative lesions. Locally invasive neoplastic lesions and PACM prevailed among PPI-treated animals. However, neither an effect on the overall mortality nor on the incidence of pre-neoplastic lesions was observed in this work.

Abstract B05: MRI provides a more reliable method of esophageal tumor detection than endoscopy in a rat model

Abstract Background: The surgical rat model of end-to-side esophagojejunal anastomosis has proven utility in terms of its ability to replicate Barrett's carcinogenesis by inducing gastroduodenoesophageal reflux (GDER). Previously, visual endoscopic analysis has been shown as a valuable tool for monitoring natural history of disease, with biopsy allowing for analysis of molecular markers while avoiding animal sacrifice. However, due to the inherent model limitation of the extraluminal presentation of the majority of tumors, as well as the small size of endoscopic biopsies, adenocarcinoma histology has only been validated post-mortem, and therefore treatment efficacy studies have been limited to chemoprevention. The current study aims to test and establish MRI and / or endoscopic visualization for diagnosis and monitoring of esophageal cancer in the rat model, in order to enhance utilization of this promising de novo model to study treatment response of novel agents in established esophageal cancer. Methods: Chronic bile and acid reflux was induced in 24 Sprague-Dawley rats through a modified Levrat's model. At 40 weeks post-surgery, all animals underwent an endoscopy, T2-weighted turbo spin-echo (TSE) MRI scan and post-mortem histological analysis. A total of five esophageal surgeons and gastroenterologists participated in a blinded study and watched endoscopy videos to determine if esophageal tumor was present. Additionally, three radiology experts participated in a blinded study designed to assess correlated coronal and axial MRI scans and determine whether tumor was present. All videos and scans were studied in triplicate, and histology was used as the gold standard to assess accuracy of each participant's analysis. Results: The accuracy of MRI and endoscopic analysis to correctly identify histology was 69.6% and 57.4%, respectively. The ROC curve analysis showed average MRI rating (AUC = 0.77, p-value = 0.032) was a better discriminator of tumor status in rats than average endoscopy rating (AUC = 0.595, p-value = 0.450). Additionally, false positive rates of MRI and endoscopy were 10.1% and 16.5%, respectively. Inter-observer variability was in substantial agreement for MRI participants (average Kappa = 0.768); whereas endoscopic analysis did not show greater agreement than that what would be expected by chance. All cases where MRI participants agreed on the presence of tumor, histology confirmed the positive findings. Conclusions: MRI is a more reliable diagnostic method than endoscopy for esophageal tumor in rats. Endoscopic examination remains a valuable tool in terms of its ability to biopsy specimens for analysis of biomarker correlates for therapeutic efficacy; however, MRI is a more dependable technique in terms of confirming tumor presence and disease progression for utilization in a treatment model. Citation Format: Juliann E. Kosovec, Yoshihiro Komatsu, Christina L. Rotoloni, Diane V. Thompson, Ali H. Zaidi, Blair A. Jobe. MRI provides a more reliable method of esophageal tumor detection than endoscopy in a rat model. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr B05.

Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR)

The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. Mean age was 55±14yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (≥40yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS+LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm³. The median FENO was 26ppb (IQR: 15-43) and 22% of SA had FENO≥50ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos≥3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu≥76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT<20 and 77% with ACQ>1.5. In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies.

Growth and remodeling of canine common iliac vein in response to venous reflux and hypertension.

The passive properties of the venous wall are important for the compliance function of the venous system. The objective of this study was to quantify the passive biomechanical response and structural growth and remodeling of veins subjected to chronic venous reflux and hypertension. To investigate the effects of venous reflux on venous mechanics, the tricuspid valve was injured in a canine model by disrupting the chordae tendineae. The conventional inflation-extension protocol in conjunction with intravascular ultrasound was used to investigate the passive biomechanical response of both control common iliac veins (n = 9 dogs) and common iliac veins subjected to 8 weeks of venous reflux and hypertension (n = 9 dogs). The changes in vein wall thickness and constituent composition were quantified by multiphoton microscopy and histologic evaluation. Biomechanical results indicate that the veins became less compliant when exposed to 8 weeks of chronic venous reflux and hypertension. The mechanical stiffening was found to be associated with a significant increase in wall thickness (P < .05) and collagen-to-elastin ratio (P < .05). After 8 weeks of chronic reflux and hypertension, the circumferential vein wall stress was significantly reduced (P < .05) because of wall thickening, although it was not restored to control levels. The growth and remodeling of the venous wall reduces the wall stress, but the stress remains higher than at baseline at 8 weeks. The compliance of the veins also decreases because of the increase in wall thickness and remodeling of the microstructure of the venous wall. These findings provide insight into potential adaptations of the venous system in reflux and hypertension.

Mucosal Impedance Discriminates GERD From Non-GERD Conditions

Current diagnostic tests for gastroesophageal reflux disease (GERD) are suboptimal and do not accurately and reliably measure chronicity of reflux. A minimally invasive device has been developed to assess esophageal mucosal impedance (MI) as a marker of chronic reflux. We performed a prospective longitudinal study to investigate MI patterns in patients with GERD and common nonreflux conditions, to assess MI patterns before and after treatment with proton pump inhibitors and to compare the performance of MI and wireless pH tests. We evaluated MI in 61 patients with erosive esophagitis, 81 with nonerosive but pH-abnormal GERD, 93 without GERD, 18 with achalasia, and 15 with eosinophilic esophagitis. MI was measured at the site of esophagitis and at 2, 5, and 10 cm above the squamocolumnar junction in all participants. MI was measured before and after acid suppressive therapy, and findings were compared with those from wireless pH monitoring. MI values were significantly lower in patients with GERD (erosive esophagitis or nonerosive but pH-abnormal GERD) or eosinophilic esophagitis than in patients without GERD or patients with achalasia (P < .001). The pattern of MI in patients with GERD differed from that in patients without GERD or patients with eosinophilic esophagitis; patients with GERD had low MI closer to the squamocolumnar junction, and values increased axially along the esophagus. These patterns normalized with acid suppressive therapy. MI patterns identified patients with esophagitis with higher levels of specificity (95%) and positive predictive values (96%) than wireless pH monitoring (64% and 40%, respectively). Based on a prospective study using a prototype device, measurements of MI detect GERD with higher levels of specificity and positive predictive values than wireless pH monitoring. Clinical Trials.gov, Number: NCT01556919.

The Effect of Dietary n6:n3 Polyunsaturated Fatty Acid Ratio on Chronic Reflux Esophagitis in Rats

Introduction: Reflux esophagitis (RE) is one of the typical lesions of gastroesophageal reflux disease (GERD). The incidence of GERD is thought related to high fat diet, while the ratio of dietary n6: n3 polyunsaturated fatty acid (PUFAs) is believed to play a role in the regulation of the inflammatory process. This study was aimed to investigate the effect of dietary n6: n3 PUFAs ratio on chronic RE in a rat model and the relationship with lipid peroxidation. Methods: Forty rats were randomly divided into 4 groups according to the n-6: n-3 PUFAs ratios in feed, including 1:1.5,10:1, 5:1 and pure n-6 PUFAs groups, and a sham operation group (10 rats, which were fed with pure n-6 PUFAs) was set up as blank control. Rat RE model (Pyloric Nylon Loop-induced Chronic Acid Reflux Esophagitis) was established by pyloric clip and section ligation. After 14 days treatment, pathological changes of the esophagus were determined, and the expression of IL-1β, IL-8, TNFα protein and mRNA in esophageal tissue homogenate were evaluated by Western blot and RT-PCR, respectively, while the MDA and SOD levels were evaluated by ELISA, respectively. Results: The food intake and body weights in the rats showed no significant difference before operation (P>0.05), while those were reduced in all groups except sham group in postoperative d7 (P<0.05) and were recovered in d14, and no intergroup differences were found (P>0.05). In PUFA1:1.5, PUFA5:1, PUFA10:1, n-6 PUFA groups and sham operation group, the postoperative d14 survival rates were 70%, 60%, 80%, 70% and 100%, respectively (P=0.306). The degree of esophagitis was lower in PUFA1:1.5 group when compared to that in the other model groups (P<0.05), but no significant difference was found among PUFA5:1, PUFA10:1 and n-6 PUFA groups(P>0.05). The protein and mRNA expression of IL-1β, IL-8 and TNFα, and the MDA levels were increased in all model groups when compared to that in sham group (P<0.05), which showed a rising tendency from PUFA1:1.5, PUFA5:1, PUFA10:1 groups to n-6 PUFA group. The SOD levels were decreased in all model groups when compared to that in sham group (P<0.05), which showed a reducing tendency from PUFA1:1.5, PUFA5:1, PUFA10:1 groups to n-6 PUFA group. Conclusion: The results indicate that the reflux related esophageal mucosal damage could be lightened by adding more n-3 PUFAs in diet, which was associated with an up-regulation of antioxidant activity and a down-regulation of lipid peroxidation in esophageal epithelium. Dietary n-6/n-3 PUFAs ratio reduction may be a beneficial strategy for gastroesophageal reflux disease management.

PO-0529 Urinary Tract Infections In Newborns

Background and aims The term urinary tract infection (UTI) in neonates implies a significant bacteriuria with symptoms of systemic infection. The gold standard for diagnosis of UTI is urine culture taken in sterile conditions. UTI incidence in general population of neonates is 0.1–2%, increasing significantly to 10% when it comes to at-risk-newborns, especially prematurely born ones. During the neonatal period, UTI incidence is higher in boys than in girls. Objectives To determine the incidence of UTI in high-risk infants, the most common causes of infection, and estimate which infants will require further urographic examination. Methods Analysis included infants with UTI who were hospitalised at the Centre for Neonatology, from 01.01.2011. to 31.12.2012. Results From 01.01.2011. to 31.12.2012, total of 1504 newborns were hospitalised at the Centre for Neonatology. UTI was verified in 85 newborns, which is 5.6% of hospitalised newborns. 64.7% of the affected were male. Most common cause of infection was E. Coli, while Klebsiella species was the second most common. UTI are more common in term newborns, while in preterm low-birth-weight-newborns UTI is mainly manifested within sepsis. Pathological ultrasound finding of urinary tract was found in 15% of the examined neonates. Conclusion Considering the fact that among the newborn population with UTI there is a significant number of children with urinary tract anomalies, which are risk factor for development of chronic pyelonephritis or reflux nephropathy, later leading to chronic renal failure and hypertension, proper detection and timely treatment of UTI in the neonatal age is of grand importance.

An Interesting Case of Esophageal Intramural Pseudodiverticulosis With Tract Formation in an HIV Patient

Introduction: Esophageal intramural pseudodiverticulosis (EIP) is a benign condition that presents as dysphagia in greater then 80% of patients. The condition is rare and pathogenesis is believed to be due to an obstruction of excretory ducts or motor disorders of the esophageal wall, each of which can lead to ductal dilation. We describe an interesting case of an HIV patient with complaints of dysphagia found to have EIP. The association of EIP with HIV is rare and has only been reported on a few occasions, but is a logical one given the propensity of HIV patients to develop esophageal Candidiasis, and the association of this fungal infection with the development of pseudodiverticula. Our patient, a 38-yearold male with HIV, presented with complaints of chest and abdominal pain. He had been experiencing progressive epigastric pain for the preceding 2 weeks described as burning, sharp, and without radiation. There was associated dysphagia to solid food, which was often followed by vomiting. Initial investigation with esophagram showed what were described as massive esophageal ulcers with fistulous communications and numerous pseudodiverticula. Upper endoscopy demonstrated multiple pseudodiverticula without any other gross abnormalities. Pathology from biopsies showed chronic inflammatory changes consistent with pseudodiverticula formation, but no evidence of infection. On repeat questioning the patient reported multiple episodes of Candidiasis in the past. Esophageal intramural pseudodiverticulosis presents as multiple flask-shaped dilations in the wall of the esophagus usually on esophogram or CT as visualization of EIP by EGD only occurs in about 20% of cases. Chronic alcoholism, diabetes mellitus, esophageal Candidiasis, and reflux disease are often reported in association with EIP, however an association with HIV has only been described a few times in the literature. We believe that difficulty visualizing pseudodiverticula on EGD and their resolution with treatment of the inciting pathology has led to underreporting of this association in the past. The extent of the tract formation seen in our patient was also very unique, as the outpouchings have generally been reported on the order of millimeters and not centimeters as seen in our case.Figure 1: Pseudodiverticulum of the middle third of the esophagus.

Acquired Double Barrel Esophagus in the Setting of Barrett’s

Introduction: Acquired double barrel esophagus, or esophagogastric fistula, is a rare endoscopic finding that has been reported in association with esophagogastric surgery, esophageal ulcer, epidermolysis bullosa dystrophica, and esophageal carcinoma. We report a case of esophageal remodeling with formation of 2 esophageal lumens in a patient with chronic reflux esophagitis and Barrett’s metaplasia. A 65-yearold male with a history of GERD (on BID Omeprazole) presented with progressively worsening dysphagia to solids, daily heartburn, and an unintentional 10-lb weight loss x 18 months. Barium esophagram revealed a longitudinal filling defect with mucosal abnormalities in the distal esophagus (Figure 1). EGD revealed a 6-cm segment of BE (C4M6), a 3-cm hiatal hernia, and extensive scarring in the distal esophagus with mucosal bridging and formation of 2 lumens in the distal 3 cm of the BE (Figure 2). Esophageal biopsies were consistent with reflux esophagitis, extensive goblet cell intestinal metaplasia, and negative for dysplasia or malignancy. Esophageal dilation was performed with improvement in symptoms. Repeat EGD with needle-knife resection of the mucosal bridge is planned in the future if dysphagia persists. In this case, the formation of an acquired esophagogastric fistula was likely due to chronic, ulcerative esophagitis with deep ulcer formation followed by granulation tissue overgrowth. Our case demonstrates a rare finding of esophageal tissue remodeling in the setting of reflux esophagitis and goblet cell metaplasia.Figure 1: Barium esophagram with mucosal abnormalities in distal esophagus.Figure 2: Endoscopic view of distal esophagus with scarring and mucosal bridging with formation of 2 lumens.

Acid reflux directly causes sleep disturbances in rat with chronic esophagitis.

Background & AimsGastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitor (PPI) therapy improves subjective but not objective sleep parameters in patients with GERD. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis.MethodsAcid reflux esophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and then wrapping the duodenum near the pylorus. Rats underwent surgery for implantation of electrodes for electroencephalogram and electromyogram recordings, and they were transferred to a soundproof recording chamber. Polygraphic recordings were scored by using 10-s epochs for wake, rapid eye movement sleep, and non-rapid eye movement (NREM) sleep. To examine the role of acid reflux, rats were subcutaneously administered a PPI, omeprazole, at a dose of 20 mg/kg once daily.ResultsRats with reflux esophagitis presented with several erosions, ulcers, and mucosal thickening with basal hyperplasia and marked inflammatory infiltration. The reflux esophagitis group showed a 34.0% increase in wake (232.2±11.4 min and 173.3±7.4 min in the reflux esophagitis and control groups, respectively; p<0.01) accompanied by a reduction in NREM sleep during light period, an increase in sleep fragmentation, and more frequent stage transitions. The use of omeprazole significantly improved sleep disturbances caused by reflux esophagitis, and this effect was not observed when the PPI was withdrawn.ConclusionsAcid reflux directly causes sleep disturbances in rats with chronic esophagitis.

The Comparison Between the Complications after Two Surgical Techniques of Esophageal Cancer

Introduction: Esophageal cancer is a common gastro intestinal malignancy. One of the most common techniques of surgery in esophageal cancer is transhiatal esophagectomy with esophagogastric anastomosis in the neck. This technique is accompanied by complications like chronic gastero-esophegeal reflux and late stenosis. This study was designed to compare the risk of complications after two surgical techniques for esophageal cancer: esophagogastric anastomosis with partial fundoplication and esophagogastric anastomosis without it. Materials and Methods: In this retrospective cohort study, 100 patients with distal two thirds of esophageal cancer who underwent transhiatal esophagectomy in Ghaem and Omid hospitals Mashhad University of Medical Sciences from 2005 to 2010 were included. Esophagogastric anastomosis to the posterior gastric wall was performed with a partial gastric fundoplication in the first group but simple routine anastomosis was done to the posterior gastric wall in the second group. Results: In a retrospective cohort study 100 patients entered the study with 59 male & 41 female and with a mean age 54.6±6.4 years. Squamous cell carcinoma was observed in 77% of the patients and adenocarcinoma was reported in 23% of them. Seventy-two percent of tumours were located in distal third and 28% were in middle third of esophagus. Esophagogastric anastomotic leakage was observed in 3 cases of fundoplication group and 7 cases of simple anastomosis technique (P=0.182) so there was no significant difference between the two groups. Benign anastomosis stricture was reported in one of the patients who underwent esophagogastric anastomosis with fundoplication, but it was observed in 8 cases with simple anastomosis technique (P=0.03) so there was a significant difference between the two groups. Conclusion: Esophagogastric anastomosis with partial fundal fundoplication is a safe technique with low incidence of anatomic leakage and late stenosis.

The value of routine gastroscopy before laparoscopic Roux-en-Y gastric bypass surgery in Chinese patients

BackgroundObesity is closely related to upper gastrointestinal diseases. China has a high incidence of gastropathy. Postoperative examination of the distal stomach becomes extremely difficult after laparoscopic Roux-en-Y gastric bypass surgery (LRYGB). Whether preoperative routine gastroscopy should be performed at all remains controversial. The objective of this study was to explore the value of routine gastroscopy before performing LRYGB in Chinese patients. MethodsThe preoperative gastroscopy reports of 180 patients who had undergone LRYGB for morbid obesity and/or metabolic syndrome in the Department of Gastrointestinal Surgery of our hospital from January 2009 to August 2013 were retrospectively analyzed. ResultsGastroscopy showed chronic superficial gastritis (n = 159, 88.3%), reflux esophagitis (n = 19, 10.6%), erosion (n = 69, 38.3%), hiatal hernia (n = 5, 2.8%), gastric ulcer (n = 3, 1.7%), duodenal ulcer (n = 32, 17.8%), and gastric polyps (n = 10, 5.6%). ConclusionIt is useful to perform gastroscopy before LRYGB. The findings of this investigation can help physicians to develop tailored therapies and procedures and thus improve the prognosis considerably. Gastroscopy should be routinely performed in Chinese patients who are planning to undergo bariatric surgery.

The Writing on the Wall: A Case of Pill Esophagitis

A 42-year-old woman with steroid-induced Cushing’s syndrome and type 2 diabetes mellitus with peripheral neuropathy was referred with a presumptive diagnosis of emphysema while on chronic prednisone therapy for 4 years, inhalable steroids, and supplemental oxygen. Her neuropathy was treated with gabapentin. She complained of worsening cough, wheezing, and some retrosternal discomfort in a recumbent position. She was diagnosed with possible reflux disease on the basis of esophagogastroduodenoscopy 5 years earlier but was not treated for it. Her pulmonary function tests including methacholine challenge were negative. High-resolution computed tomography scan of the chest showed scattered areas of ground glass opacity through the lungs but no signs of emphysema. Alpha1-antitrypsin level was normal. Chronic esophageal reflux disease was suspected, and during repeat esophagogastroduodenoscopy, mild pill esophagitis was noted, with lettering seen on the esophageal mucosa (Figures A, B). The imprint was then removed easily with saline washing. The culprit was identified as a gabapentin pill by the analysis of the letters from the esophageal wall because, literally, the writing was on the wall (Figure C). The patient improved with conservative therapy.

Increased immunoreactivity of cathepsins in the rat esophagus under chronic acid reflux esophagitis.

We have designed a stable rat chronic acid reflux esophagitis (RE) model. In gastrointestinal lesions, several lysosomal cathepsins are known to participate in epithelial permeability in cell-cell connections, such as tight junctions in ulcerative colitis. However, very few studies have focused on the distribution of cathepsins in the esophageal multilayer squamous epithelium. Therefore to clarify the role of cathepsins in RE, we investigated their immunohistological localization in the esophageal epithelium under normal conditions and after RE. Of the cathepsins examined (cathepsins B, C, D, F, H, L, S, and X), granular immunoreactivity for cathepsins B, C, D and L was observed in the control esophageal epithelia; although, their distribution differed depending on the enzyme examined. In the RE model, immunoreactivity of these cathepsins was increased in esophageal epithelial cells and activated macrophages. The immunoreactivity for cathepsins F, H, S and X was barely detectable in the control esophageal epithelium. However, in the RE model, we noticed a slight increase in the expression of cathepsins H and X in the epithelial cells. Furthermore, activated macrophages of the RE model possessed intense immunoreactivity for these cathepsins, which may have been related to esophageal inflammatory mechanisms.

Impact of histone deacetylase 1 and metastasis-associated gene 1 expression in esophageal carcinogenesis.

Animal models are important for the development of novel therapies for esophageal cancer. Histone deacetylase 1 (HDAC1)/metastasis-associated gene (MTA1) complexes inhibit p53 acetylation and thus, inhibit p53-induced apoptosis. The aim of the present study was to evaluate HDAC1 and MTA1 expression in esophageal carcinogenesis in rats. The rats underwent a total gastrectomy followed by esophagojejunostomy to induce chronic duodenal content reflux esophagitis. The rats were sacrificed sequentially at 20, 30, 40 and 50 weeks post-surgery and the esophagi were examined. Immunohistochemical analysis was conducted to assess the expression and localization of HDAC1 and MTA1. At 20 weeks post-surgery, squamous proliferative hyperplasia and Barrett’s metaplasia (BM) were observed. While, adenocarcinoma-associated BM and squamous cell carcinoma were observed at 30–50 weeks post-surgery. The nuclear expression of HDAC1 and MTA1 was observed in all of the stages of squamous carcinogenesis and adenocarcinogenesis, although not in the normal esophageal epithelium. The expression of HDAC1 and MTA1 may be involved in duodenoesophageal reflux-induced neoplastic transformation of the esophageal mucosa into cancer cells with squamous and adeno differentiation.

Sa1878 Individuals With Portal Hypertension Have an Increased Propensity to Develop Hyperplastic Gastric Polyps

Background and goals: Recently we observed patients with chronic liver diseases (CLD) (n= 16) and chronic reflux symptoms (CRS) (n=38) that developed gastric polyps (GPs) while undergoing repeated esophagogastroduodenoscopy (EGD). The indications for repeated EGD were: persistent reflux symptoms (CRS patients) and monitoring of esophageal varices development (CLD patients). Herewith we identify risk factors for GP development and estimate the gastric polyp development time (GPDT). Methods: Data was retrospectively analyzed. GPDT was defined as days, since the first gastroscopy until polyp discovery. The presence of portal hypertension (PHT) in CLD patients was determined by the presence of esophageal varices with or without gastric varices. Results: CLD patients developed more hyperplastic gastric polyps (HGPs) than CRS patients (p= 0.021). CLD patients with PHT developed HGPs at a younger age (p=0.023) and had a tendency for a shorter GPDT than CLD patients without PHT: mean GPDT was 1184 ±787 days (for CLD patients with PHT) vs.2634 ±2345 days (for CLD patients without PHT). In order to further study the effect of PHT on the GPDT, Kaplan-Meier curves, indicating the individual GPDT, for all patients with HGPs, from the CRS and CLD groups, were constructed. A trend for shorter GPDT for CLD patients with PHT was demonstrated (Figure 1). In the CLD patients (irrespective to the presence PHT), a positive correlation between the GPDT and age was found; the older the patient, the longer the GPDT (p=0.014). In patients with CLD, Ki-67 labeling index values of HGPs were independent to the presence PHT, the patient's gender, to infection with Helicobacter Pylori and to PPI exposure. However, a negative correlation between the patient's age and the Ki-67 values was found; the younger the patient, the higher the Ki-67 value (p= 0.042).The histopathology features that were previously reported to be specific for GP tissue in patients with PHT were not detected more often in the CLD patients with HGPs, irrespective to the presence or absence of PHT. Conclusions: Compared to CRS patients, CLD patients with PHT, appear to develop HGPs at a greater number, at a younger age and in a shorter GPDT.

Sa1879 A Model to Assess the Risk for ASA/NSAID-Related Ulcer Bleeding for the Individual Patient Based on the Number of Risk Factors

Background and goals: Recently we observed patients with chronic liver diseases (CLD) (n= 16) and chronic reflux symptoms (CRS) (n=38) that developed gastric polyps (GPs) while undergoing repeated esophagogastroduodenoscopy (EGD). The indications for repeated EGD were: persistent reflux symptoms (CRS patients) and monitoring of esophageal varices development (CLD patients). Herewith we identify risk factors for GP development and estimate the gastric polyp development time (GPDT). Methods: Data was retrospectively analyzed. GPDT was defined as days, since the first gastroscopy until polyp discovery. The presence of portal hypertension (PHT) in CLD patients was determined by the presence of esophageal varices with or without gastric varices. Results: CLD patients developed more hyperplastic gastric polyps (HGPs) than CRS patients (p= 0.021). CLD patients with PHT developed HGPs at a younger age (p=0.023) and had a tendency for a shorter GPDT than CLD patients without PHT: mean GPDT was 1184 ±787 days (for CLD patients with PHT) vs.2634 ±2345 days (for CLD patients without PHT). In order to further study the effect of PHT on the GPDT, Kaplan-Meier curves, indicating the individual GPDT, for all patients with HGPs, from the CRS and CLD groups, were constructed. A trend for shorter GPDT for CLD patients with PHT was demonstrated (Figure 1). In the CLD patients (irrespective to the presence PHT), a positive correlation between the GPDT and age was found; the older the patient, the longer the GPDT (p=0.014). In patients with CLD, Ki-67 labeling index values of HGPs were independent to the presence PHT, the patient's gender, to infection with Helicobacter Pylori and to PPI exposure. However, a negative correlation between the patient's age and the Ki-67 values was found; the younger the patient, the higher the Ki-67 value (p= 0.042).The histopathology features that were previously reported to be specific for GP tissue in patients with PHT were not detected more often in the CLD patients with HGPs, irrespective to the presence or absence of PHT. Conclusions: Compared to CRS patients, CLD patients with PHT, appear to develop HGPs at a greater number, at a younger age and in a shorter GPDT.

Advanced Imaging in Barrett's esophagus

Barrett’s Esophagus (BE) is a metaplastic change in the esophagus that results in replacement of the normal squamous lined epithelium with intestinal metaplasia. The incidence of esophageal adenocarcinoma has rapidly increased in recent years and BE has been found to be present as a precursor lesion in many of these cases. Patient’s with BE are thought to have an annual risk of developing esophageal cancer of 0.5% per year, substantially higher than the general population, but the absolute risk of developing cancer in BE patients is low. Endoscopic screening of subjects with chronic reflux symptoms has been recommended as a method of detecting BE and early cancer and despite the lack of clinical evidence, BE patients are then routinely enrolled in surveillance programs.